an evaluation of various direct compression ingredients using the gamlen tablet press gtp-1
DESCRIPTION
We have shown previously that the Gamlen Tablet Press GTP-1 can rapidly evaluate formulations for tablet development using milligram quantities of material. Uniquely for a tablet press it gives precise information on the compression force, ejection force and fracture force of an individual tablet, providing valuable information for the required target product profile, required for Quality by Design (QbD). We present in this work an evaluation of a number of different direct compression excipients in the development of a paracetamol tablet. We evaluated a number of different direct compression excipients to prepare a formulation containing 10% paracetamol. The formulations were blended for 30 minutes and lubricated with 0.5% magnesium stearate for a further 5 minutes in a blender. Each formulation was then compacted using the Gamlen Tablet Press GTP-1 to produce round flat face tablets. Tablets weresubjected to tensile strength, friability and disintegration testing, whilst the formulation was tested for flowability and LOD. The initial experiments showed clear differences between formulations in compressibility, friability, disintegration and powder flowability. Among the mannitol grades the compressibility of the SD types was better than the DC types. Very high ejection forces were recorded despite use of a lubricant. Individual ejection profiles analysed by the GTP-1 revealed the important relationship of material properties with ejection of the tablet from the die- a key determinant of suitability for rotary press manufacture. The main experiments characterised the compressibility and tablet behaviour of the most compressible excipients, with the low API% formulas performing best. Evaluation of a wide range of formulations using using the GTP-1 provided valuable information on compression force, ejection force and disintegration times of individual tablets using very small amounts of material. This enables an evaluation of the widest possible tablet quality and tablet/ material processing parameters to aid formulation development.TRANSCRIPT
AN EVALUATION OF VARIOUS DIRECT COMPRESSION INGREDIENTS USING THE GAMLEN TABLET PRESS GTP-1
DIPANKAR DEY, MICHAEL GAMLEN, GAMLEN TABLETING LTD, BIOCITY NOTTINGHAM, NOTTINGHAM UK NG1 1GF
The modern tablet needs to satisfy a number of parameters that make it fit for purpose such as hardness, potency, friability and dissolution as well as be suitable for commercial manufacture using a rotary tablet press. Performing a sufficient number of experiments to optimise the formulation is often limited by the quantity of API available and the nature of the equipment used. We present here an approach to tablet formulation using a novel bench top computer controlled tablet press—the Gamlen Tablet Press GTP-1. This requires only milligram quantities of material, is objective and practical. The approach is based on establishing the compressibility of the formulation as determined by tablet tensile strength measurements using the diametral compression test (Fell &Newton) over a range of compression pressures ; Tensile strength is an objective measure of tablet strength as it takes into account both hardness and tablet thickness. As such it can be used to compare tablets of different shapes and sizes (Pitt &Heasley 2012). In addition we can also measure ejection stress associated with each formulation from the ejection force normalised with tablet thickness.
In the preliminary experiment the Galen IQ, Parteck SD and Perlitol SD grades were the most compressible whilst the Perlitol DC grades had the least. All formulations showed high ejection stress. We selected the 200 mesh size of each brand for further development with L-HPC21 in the Main experiments. The L-HPC21 substantially increased compressibility, and also reduced ejection stress and friability The drug percentage had a major effect in reducing compressibility particularly for the Galen IQ. Using The combination of results gained on compressibility combined with powder flow and ejection stress results give a useful screening method when selecting the formulation of choice. We assigned the gradient of the tensile strength v compression pressure profiles as the compressibility of the formulation. When plotted against the powder flowability for each formulation we can visualise the results as a ‘Decision Matrix’. The Galen 0.1%/1% + L-HPC21 exhibit the best combination of compressibility and flow behaviour. In this work we have shown that rapid screening of formulations using the Gamlen Tablet Press GTP-1 is a very useful approach to development of the required tablet profile using the compression gradient as a measure of compressibility. We propose that this be considered as a Critical Quality Attribute of a tablet formulation in the tablet Quality by Design paradigm.
The formulation was developed in two stages. Preliminary experiments determined the compressibility of a formulation containing the drug (acetaminophen), excipient and lubricant; ten excipients and excipient grades were evaluated on a 100g scale. In the main experiments we used the best formulations, selected using tensile fracture strength/compaction pressure profiles. To improve compressibility we added 20% L-HPC21 (Shin-Etsu). The magnesium stearate concentration was kept at 0.5%w/w. All formulations were made using the Gamlen Tablet Press GTP-1 (Nottingham UK) to produce 75mg round flat face tablets. The tablets were subjected to tensile fracture stress testing on the GTP-1, friability and disintegration measurements. Ejection stress was also recorded for each tablet.
Fell JT and Newton JM. Determination of tablet strength by the diametral compression test. J Pharm Sci 59; 688-691, 1970 Pitt & Heasley. Powder Technology 2012. http://dx.doi.org/10.1016/j.powtec.2011.12.060)
BACKGROUND AND APPROACH
APPROACH
MATERIALS AND METHODS
RESULTS
DISCUSSION AND CONCLUSION
REFERENCES
Preliminary Experiments
σt is the tensile fracture strength of the tablet, P is the fracture force (N), D is the tablet diameter, t is the overall thickness
Mannitol grade Parteck (Merck)
Mannitol grade Perlitol (Roquette)
Isomaltulose (Beneo-Palatinit)
Parteck M100
Perlitol 100SD
Galen IQ720
Parteck M200
Perlitol 200SD
Galen IQ721
Parteck M300
Perlitol 300DC
Perlitol 400DC
Perlitol 500DC
Main Experiments We have shown previously that the Gamlen Tablet Press GTP-1 can rapidly evaluate formulations for tablet development using milligram quantities of material. Uniquely for a tablet press it gives precise information on the compression force, ejection force and fracture force of an individual tablet, providing valuable information for the required target product profile, required for Quality by Design (QbD). We present in this work an evaluation of a number of different direct compression excipients in the development of a paracetamol tablet. We evaluated a number of different direct compression excipients to prepare a formulation containing 10% paracetamol. The formulations were blended for 30 minutes and lubricated with 0.5% magnesium stearate for a further 5 minutes in a blender. Each formulation was then compacted using the Gamlen Tablet Press GTP-1 to produce round flat face tablets. Tablets weresubjected to tensile strength, friability and disintegration testing, whilst the formulation was tested for flowability and LOD. The initial experiments showed clear differences between formulations in compressibility, friability, disintegration and powder flowability. Among the mannitol grades the compressibility of the SD types was better than the DC types. Very high ejection forces were recorded despite use of a lubricant. Individual ejection profiles analysed by the GTP-1 revealed the important relationship of material properties with ejection of the tablet from the die- a key determinant of suitability for rotary press manufacture. The main experiments characterised the compressibility and tablet behaviour of the most compressible excipients, with the low API% formulas performing best. Evaluation of a wide range of formulations using using the GTP-1 provided valuable information on compression force, ejection force and disintegration times of individual tablets using very small amounts of material. This enables an evaluation of the widest possible tablet quality and tablet/ material processing parameters to aid formulation development.
ABSTRACT
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck M100
14.5 16 0.27
Parteck M200
12.9 20 0.17
Parteck M300
7.4 14 0.19
Perlitol 100SD
13.5 20 0.16
Perlitol 200SD
11.63 18 0.11
Perlitol 300DC
8.3 10 0.14
Perlitol 400DC
6.7 8 0.11
Perlitol 500DC
8.1 5 0.14
Galen IQ720
11.25 16 4.07
Galen IQ721
13.4 12 1.5
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck 0.1% 16.25 18 0.81
Parteck 1% 16.25 16 1.13
Parteck 10% 17.5 22 1.10
Perlitol 0.1% 11.25 12 0.96
Perlitol 1% 8.75 16 0.98
Perlitol 10% 16.25 18 1.32
Galen 0.1% 13.75 7 2.70
Galen 1% 16.25 8 2.65
Galen 10% 16.25 20 2.21
AN EVALUATION OF VARIOUS DIRECT COMPRESSION INGREDIENTS USING THE GAMLEN TABLET PRESS GTP-1
DIPANKAR DEY, MICHAEL GAMLEN, GAMLEN TABLETING LTD, BIOCITY NOTTINGHAM, NOTTINGHAM UK NG1 1GF
ABSTRACT
We have shown previously that the Gamlen Tablet Press GTP-1 can rapidly evaluate formulations for tablet development using milligram quantities of material. Uniquely for a tablet press it gives precise information on the compression force, ejection force and fracture force of an individual tablet, providing valuable information for the required target product profile, required for Quality by Design (QbD). We present in this work an evaluation of a number of different direct compression excipients in the development of a paracetamol tablet. We evaluated a number of different direct compression excipients to prepare a formulation containing 10% paracetamol. The formulations were blended for 30 minutes and lubricated with 0.5% magnesium stearate for a further 5 minutes in a blender. Each formulation was then compacted using the Gamlen Tablet Press GTP-1 to produce round flat face tablets. Tablets weresubjected to tensile strength, friability and disintegration testing, whilst the formulation was tested for flowability and LOD. The initial experiments showed clear differences between formulations in compressibility, friability, disintegration and powder flowability. Among the mannitol grades the compressibility of the SD types was better than the DC types. Very high ejection forces were recorded despite use of a lubricant. Individual ejection profiles analysed by the GTP-1 revealed the important relationship of material properties with ejection of the tablet from the die- a key determinant of suitability for rotary press manufacture. The main experiments characterised the compressibility and tablet behaviour of the most compressible excipients, with the low API% formulas performing best. Evaluation of a wide range of formulations using using the GTP-1 provided valuable information on compression force, ejection force and disintegration times of individual tablets using very small amounts of material. This enables an evaluation of the widest possible tablet quality and tablet / material processing parameters to aid formulation development.
BACKGROUND AND APPROACH
The modern tablet needs to satisfy a number of parameters that make it fit for purpose such as hardness, potency, friability and dissolution as well as be suitable for commercial manufacture using a rotary tablet press. Performing a sufficient number of experiments to optimise the formulation is often limited by the quantity of API available and the nature of the equipment used. We present here an approach to tablet formulation using a novel bench top computer controlled tablet press—the Gamlen Tablet Press GTP-1. This requires only milligram quantities of material, is objective and practical. The approach is based on establishing the compressibility of the formulation as determined by tablet tensile strength measurements using the diametral compression test (Fell &Newton) over a range of compression pressures ;
σt =2PπDt
σt is the tensile fracture strength of the tablet, P is the fracture force (N), D is the tablet diameter, t is the overall thickness
Tensile strength is an objective measure of tablet strength as it takes into account both hardness and tablet thickness. As such it can be used to compare tablets of different shapes and sizes (Pitt &Heasley 2012). In addition we can also measure ejection stress associated with each formulation from the ejection force normalised with tablet thickness.
MATERIALS AND METHODS
The formulation was developed in two stages. Preliminary experiments determined the compressibility of a formulation containing the drug (acetaminophen), excipient and lubricant; ten excipients and excipient grades were evaluated on a 100g scale. In the main experiments we used the best formulations, selected using tensile fracture strength/compaction pressure profiles. To
improve compressibility we added 20% L-HPC21 (Shin-Etsu).The magnesium stearate concentration was kept at 0.5%w/w. All formulations were made using the Gamlen Tablet Press GTP-1 (Nottingham UK) to produce 75mg round flat face tablets. The tablets were subjected to tensile fracture stress testing on the GTP-1, friability and disintegration measurements. Ejection stress was also recorded for each tablet.
Mannitol grade Parteck (Merck)
Mannitol grade Perlitol
(Roquette)
Isomaltulose (Beneo- Palatinit)
Parteck M100 Perlitol 100SD Galen IQ720
Parteck M200 Perlitol 200SD Galen IQ721
Perlitol 300DC
Perlitol 400DC
Perlitol 500DC
thickness
thickness
6mm
3mm
Hardness Test
AN EVALUATION OF VARIOUS DIRECT COMPRESSION INGREDIENTS USING THE GAMLEN TABLET PRESS GTP-1
DIPANKAR DEY, MICHAEL GAMLEN, GAMLEN TABLETING LTD, BIOCITY NOTTINGHAM, NOTTINGHAM UK NG1 1GF
The modern tablet needs to satisfy a number of parameters that make it fit for purpose such as hardness, potency, friability and dissolution as well as be suitable for commercial manufacture using a rotary tablet press. Performing a sufficient number of experiments to optimise the formulation is often limited by the quantity of API available and the nature of the equipment used. We present here an approach to tablet formulation using a novel bench top computer controlled tablet press—the Gamlen Tablet Press GTP-1. This requires only milligram quantities of material, is objective and practical. The approach is based on establishing the compressibility of the formulation as determined by tablet tensile strength measurements using the diametral compression test (Fell &Newton) over a range of compression pressures ; Tensile strength is an objective measure of tablet strength as it takes into account both hardness and tablet thickness. As such it can be used to compare tablets of different shapes and sizes (Pitt &Heasley 2012). In addition we can also measure ejection stress associated with each formulation from the ejection force normalised with tablet thickness.
In the preliminary experiment the Galen IQ, Parteck SD and Perlitol SD grades were the most compressible whilst the Perlitol DC grades had the least. All formulations showed high ejection stress. We selected the 200 mesh size of each brand for further development with L-HPC21 in the Main experiments. The L-HPC21 substantially increased compressibility, and also reduced ejection stress and friability The drug percentage had a major effect in reducing compressibility particularly for the Galen IQ. Using The combination of results gained on compressibility combined with powder flow and ejection stress results give a useful screening method when selecting the formulation of choice. We assigned the gradient of the tensile strength v compression pressure profiles as the compressibility of the formulation. When plotted against the powder flowability for each formulation we can visualise the results as a ‘Decision Matrix’. The Galen 0.1%/1% + L-HPC21 exhibit the best combination of compressibility and flow behaviour. In this work we have shown that rapid screening of formulations using the Gamlen Tablet Press GTP-1 is a very useful approach to development of the required tablet profile using the compression gradient as a measure of compressibility. We propose that this be considered as a Critical Quality Attribute of a tablet formulation in the tablet Quality by Design paradigm.
The formulation was developed in two stages. Preliminary experiments determined the compressibility of a formulation containing the drug (acetaminophen), excipient and lubricant; ten excipients and excipient grades were evaluated on a 100g scale. In the main experiments we used the best formulations, selected using tensile fracture strength/compaction pressure profiles. To improve compressibility we added 20% L-HPC21 (Shin-Etsu). The magnesium stearate concentration was kept at 0.5%w/w. All formulations were made using the Gamlen Tablet Press GTP-1 (Nottingham UK) to produce 75mg round flat face tablets. The tablets were subjected to tensile fracture stress testing on the GTP-1, friability and disintegration measurements. Ejection stress was also recorded for each tablet.
Fell JT and Newton JM. Determination of tablet strength by the diametral compression test. J Pharm Sci 59; 688-691, 1970 Pitt & Heasley. Powder Technology 2012. http://dx.doi.org/10.1016/j.powtec.2011.12.060)
BACKGROUND AND APPROACH
APPROACH
MATERIALS AND METHODS
RESULTS
DISCUSSION AND CONCLUSION
REFERENCES
Preliminary Experiments
σt is the tensile fracture strength of the tablet, P is the fracture force (N), D is the tablet diameter, t is the overall thickness
Mannitol grade Parteck (Merck)
Mannitol grade Perlitol (Roquette)
Isomaltulose (Beneo-Palatinit)
Parteck M100
Perlitol 100SD
Galen IQ720
Parteck M200
Perlitol 200SD
Galen IQ721
Parteck M300
Perlitol 300DC
Perlitol 400DC
Perlitol 500DC
Main Experiments We have shown previously that the Gamlen Tablet Press GTP-1 can rapidly evaluate formulations for tablet development using milligram quantities of material. Uniquely for a tablet press it gives precise information on the compression force, ejection force and fracture force of an individual tablet, providing valuable information for the required target product profile, required for Quality by Design (QbD). We present in this work an evaluation of a number of different direct compression excipients in the development of a paracetamol tablet. We evaluated a number of different direct compression excipients to prepare a formulation containing 10% paracetamol. The formulations were blended for 30 minutes and lubricated with 0.5% magnesium stearate for a further 5 minutes in a blender. Each formulation was then compacted using the Gamlen Tablet Press GTP-1 to produce round flat face tablets. Tablets weresubjected to tensile strength, friability and disintegration testing, whilst the formulation was tested for flowability and LOD. The initial experiments showed clear differences between formulations in compressibility, friability, disintegration and powder flowability. Among the mannitol grades the compressibility of the SD types was better than the DC types. Very high ejection forces were recorded despite use of a lubricant. Individual ejection profiles analysed by the GTP-1 revealed the important relationship of material properties with ejection of the tablet from the die- a key determinant of suitability for rotary press manufacture. The main experiments characterised the compressibility and tablet behaviour of the most compressible excipients, with the low API% formulas performing best. Evaluation of a wide range of formulations using using the GTP-1 provided valuable information on compression force, ejection force and disintegration times of individual tablets using very small amounts of material. This enables an evaluation of the widest possible tablet quality and tablet/ material processing parameters to aid formulation development.
ABSTRACT
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck M100
14.5 16 0.27
Parteck M200
12.9 20 0.17
Parteck M300
7.4 14 0.19
Perlitol 100SD
13.5 20 0.16
Perlitol 200SD
11.63 18 0.11
Perlitol 300DC
8.3 10 0.14
Perlitol 400DC
6.7 8 0.11
Perlitol 500DC
8.1 5 0.14
Galen IQ720
11.25 16 4.07
Galen IQ721
13.4 12 1.5
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck 0.1% 16.25 18 0.81
Parteck 1% 16.25 16 1.13
Parteck 10% 17.5 22 1.10
Perlitol 0.1% 11.25 12 0.96
Perlitol 1% 8.75 16 0.98
Perlitol 10% 16.25 18 1.32
Galen 0.1% 13.75 7 2.70
Galen 1% 16.25 8 2.65
Galen 10% 16.25 20 2.21
US_Letter_Poster1.indd 1 06/10/2012 12:28
RESULTS
AN EVALUATION OF VARIOUS DIRECT COMPRESSION INGREDIENTS USING THE GAMLEN TABLET PRESS GTP-1
DIPANKAR DEY, MICHAEL GAMLEN, GAMLEN TABLETING LTD, BIOCITY NOTTINGHAM, NOTTINGHAM UK NG1 1GF
The modern tablet needs to satisfy a number of parameters that make it fit for purpose such as hardness, potency, friability and dissolution as well as be suitable for commercial manufacture using a rotary tablet press. Performing a sufficient number of experiments to optimise the formulation is often limited by the quantity of API available and the nature of the equipment used. We present here an approach to tablet formulation using a novel bench top computer controlled tablet press—the Gamlen Tablet Press GTP-1. This requires only milligram quantities of material, is objective and practical. The approach is based on establishing the compressibility of the formulation as determined by tablet tensile strength measurements using the diametral compression test (Fell &Newton) over a range of compression pressures ; Tensile strength is an objective measure of tablet strength as it takes into account both hardness and tablet thickness. As such it can be used to compare tablets of different shapes and sizes (Pitt &Heasley 2012). In addition we can also measure ejection stress associated with each formulation from the ejection force normalised with tablet thickness.
In the preliminary experiment the Galen IQ, Parteck SD and Perlitol SD grades were the most compressible whilst the Perlitol DC grades had the least. All formulations showed high ejection stress. We selected the 200 mesh size of each brand for further development with L-HPC21 in the Main experiments. The L-HPC21 substantially increased compressibility, and also reduced ejection stress and friability The drug percentage had a major effect in reducing compressibility particularly for the Galen IQ. Using The combination of results gained on compressibility combined with powder flow and ejection stress results give a useful screening method when selecting the formulation of choice. We assigned the gradient of the tensile strength v compression pressure profiles as the compressibility of the formulation. When plotted against the powder flowability for each formulation we can visualise the results as a ‘Decision Matrix’. The Galen 0.1%/1% + L-HPC21 exhibit the best combination of compressibility and flow behaviour. In this work we have shown that rapid screening of formulations using the Gamlen Tablet Press GTP-1 is a very useful approach to development of the required tablet profile using the compression gradient as a measure of compressibility. We propose that this be considered as a Critical Quality Attribute of a tablet formulation in the tablet Quality by Design paradigm.
The formulation was developed in two stages. Preliminary experiments determined the compressibility of a formulation containing the drug (acetaminophen), excipient and lubricant; ten excipients and excipient grades were evaluated on a 100g scale. In the main experiments we used the best formulations, selected using tensile fracture strength/compaction pressure profiles. To improve compressibility we added 20% L-HPC21 (Shin-Etsu). The magnesium stearate concentration was kept at 0.5%w/w. All formulations were made using the Gamlen Tablet Press GTP-1 (Nottingham UK) to produce 75mg round flat face tablets. The tablets were subjected to tensile fracture stress testing on the GTP-1, friability and disintegration measurements. Ejection stress was also recorded for each tablet.
Fell JT and Newton JM. Determination of tablet strength by the diametral compression test. J Pharm Sci 59; 688-691, 1970 Pitt & Heasley. Powder Technology 2012. http://dx.doi.org/10.1016/j.powtec.2011.12.060)
BACKGROUND AND APPROACH
APPROACH
MATERIALS AND METHODS
RESULTS
DISCUSSION AND CONCLUSION
REFERENCES
Preliminary Experiments
σt is the tensile fracture strength of the tablet, P is the fracture force (N), D is the tablet diameter, t is the overall thickness
Mannitol grade Parteck (Merck)
Mannitol grade Perlitol (Roquette)
Isomaltulose (Beneo-Palatinit)
Parteck M100
Perlitol 100SD
Galen IQ720
Parteck M200
Perlitol 200SD
Galen IQ721
Parteck M300
Perlitol 300DC
Perlitol 400DC
Perlitol 500DC
Main Experiments We have shown previously that the Gamlen Tablet Press GTP-1 can rapidly evaluate formulations for tablet development using milligram quantities of material. Uniquely for a tablet press it gives precise information on the compression force, ejection force and fracture force of an individual tablet, providing valuable information for the required target product profile, required for Quality by Design (QbD). We present in this work an evaluation of a number of different direct compression excipients in the development of a paracetamol tablet. We evaluated a number of different direct compression excipients to prepare a formulation containing 10% paracetamol. The formulations were blended for 30 minutes and lubricated with 0.5% magnesium stearate for a further 5 minutes in a blender. Each formulation was then compacted using the Gamlen Tablet Press GTP-1 to produce round flat face tablets. Tablets weresubjected to tensile strength, friability and disintegration testing, whilst the formulation was tested for flowability and LOD. The initial experiments showed clear differences between formulations in compressibility, friability, disintegration and powder flowability. Among the mannitol grades the compressibility of the SD types was better than the DC types. Very high ejection forces were recorded despite use of a lubricant. Individual ejection profiles analysed by the GTP-1 revealed the important relationship of material properties with ejection of the tablet from the die- a key determinant of suitability for rotary press manufacture. The main experiments characterised the compressibility and tablet behaviour of the most compressible excipients, with the low API% formulas performing best. Evaluation of a wide range of formulations using using the GTP-1 provided valuable information on compression force, ejection force and disintegration times of individual tablets using very small amounts of material. This enables an evaluation of the widest possible tablet quality and tablet/ material processing parameters to aid formulation development.
ABSTRACT
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck M100
14.5 16 0.27
Parteck M200
12.9 20 0.17
Parteck M300
7.4 14 0.19
Perlitol 100SD
13.5 20 0.16
Perlitol 200SD
11.63 18 0.11
Perlitol 300DC
8.3 10 0.14
Perlitol 400DC
6.7 8 0.11
Perlitol 500DC
8.1 5 0.14
Galen IQ720
11.25 16 4.07
Galen IQ721
13.4 12 1.5
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck 0.1% 16.25 18 0.81
Parteck 1% 16.25 16 1.13
Parteck 10% 17.5 22 1.10
Perlitol 0.1% 11.25 12 0.96
Perlitol 1% 8.75 16 0.98
Perlitol 10% 16.25 18 1.32
Galen 0.1% 13.75 7 2.70
Galen 1% 16.25 8 2.65
Galen 10% 16.25 20 2.21
AN EVALUATION OF VARIOUS DIRECT COMPRESSION INGREDIENTS USING THE GAMLEN TABLET PRESS GTP-1
DIPANKAR DEY, MICHAEL GAMLEN, GAMLEN TABLETING LTD, BIOCITY NOTTINGHAM, NOTTINGHAM UK NG1 1GF
The modern tablet needs to satisfy a number of parameters that make it fit for purpose such as hardness, potency, friability and dissolution as well as be suitable for commercial manufacture using a rotary tablet press. Performing a sufficient number of experiments to optimise the formulation is often limited by the quantity of API available and the nature of the equipment used. We present here an approach to tablet formulation using a novel bench top computer controlled tablet press—the Gamlen Tablet Press GTP-1. This requires only milligram quantities of material, is objective and practical. The approach is based on establishing the compressibility of the formulation as determined by tablet tensile strength measurements using the diametral compression test (Fell &Newton) over a range of compression pressures ; Tensile strength is an objective measure of tablet strength as it takes into account both hardness and tablet thickness. As such it can be used to compare tablets of different shapes and sizes (Pitt &Heasley 2012). In addition we can also measure ejection stress associated with each formulation from the ejection force normalised with tablet thickness.
In the preliminary experiment the Galen IQ, Parteck SD and Perlitol SD grades were the most compressible whilst the Perlitol DC grades had the least. All formulations showed high ejection stress. We selected the 200 mesh size of each brand for further development with L-HPC21 in the Main experiments. The L-HPC21 substantially increased compressibility, and also reduced ejection stress and friability The drug percentage had a major effect in reducing compressibility particularly for the Galen IQ. Using The combination of results gained on compressibility combined with powder flow and ejection stress results give a useful screening method when selecting the formulation of choice. We assigned the gradient of the tensile strength v compression pressure profiles as the compressibility of the formulation. When plotted against the powder flowability for each formulation we can visualise the results as a ‘Decision Matrix’. The Galen 0.1%/1% + L-HPC21 exhibit the best combination of compressibility and flow behaviour. In this work we have shown that rapid screening of formulations using the Gamlen Tablet Press GTP-1 is a very useful approach to development of the required tablet profile using the compression gradient as a measure of compressibility. We propose that this be considered as a Critical Quality Attribute of a tablet formulation in the tablet Quality by Design paradigm.
The formulation was developed in two stages. Preliminary experiments determined the compressibility of a formulation containing the drug (acetaminophen), excipient and lubricant; ten excipients and excipient grades were evaluated on a 100g scale. In the main experiments we used the best formulations, selected using tensile fracture strength/compaction pressure profiles. To improve compressibility we added 20% L-HPC21 (Shin-Etsu). The magnesium stearate concentration was kept at 0.5%w/w. All formulations were made using the Gamlen Tablet Press GTP-1 (Nottingham UK) to produce 75mg round flat face tablets. The tablets were subjected to tensile fracture stress testing on the GTP-1, friability and disintegration measurements. Ejection stress was also recorded for each tablet.
Fell JT and Newton JM. Determination of tablet strength by the diametral compression test. J Pharm Sci 59; 688-691, 1970 Pitt & Heasley. Powder Technology 2012. http://dx.doi.org/10.1016/j.powtec.2011.12.060)
BACKGROUND AND APPROACH
APPROACH
MATERIALS AND METHODS
RESULTS
DISCUSSION AND CONCLUSION
REFERENCES
Preliminary Experiments
σt is the tensile fracture strength of the tablet, P is the fracture force (N), D is the tablet diameter, t is the overall thickness
Mannitol grade Parteck (Merck)
Mannitol grade Perlitol (Roquette)
Isomaltulose (Beneo-Palatinit)
Parteck M100
Perlitol 100SD
Galen IQ720
Parteck M200
Perlitol 200SD
Galen IQ721
Parteck M300
Perlitol 300DC
Perlitol 400DC
Perlitol 500DC
Main Experiments We have shown previously that the Gamlen Tablet Press GTP-1 can rapidly evaluate formulations for tablet development using milligram quantities of material. Uniquely for a tablet press it gives precise information on the compression force, ejection force and fracture force of an individual tablet, providing valuable information for the required target product profile, required for Quality by Design (QbD). We present in this work an evaluation of a number of different direct compression excipients in the development of a paracetamol tablet. We evaluated a number of different direct compression excipients to prepare a formulation containing 10% paracetamol. The formulations were blended for 30 minutes and lubricated with 0.5% magnesium stearate for a further 5 minutes in a blender. Each formulation was then compacted using the Gamlen Tablet Press GTP-1 to produce round flat face tablets. Tablets weresubjected to tensile strength, friability and disintegration testing, whilst the formulation was tested for flowability and LOD. The initial experiments showed clear differences between formulations in compressibility, friability, disintegration and powder flowability. Among the mannitol grades the compressibility of the SD types was better than the DC types. Very high ejection forces were recorded despite use of a lubricant. Individual ejection profiles analysed by the GTP-1 revealed the important relationship of material properties with ejection of the tablet from the die- a key determinant of suitability for rotary press manufacture. The main experiments characterised the compressibility and tablet behaviour of the most compressible excipients, with the low API% formulas performing best. Evaluation of a wide range of formulations using using the GTP-1 provided valuable information on compression force, ejection force and disintegration times of individual tablets using very small amounts of material. This enables an evaluation of the widest possible tablet quality and tablet/ material processing parameters to aid formulation development.
ABSTRACT
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck M100
14.5 16 0.27
Parteck M200
12.9 20 0.17
Parteck M300
7.4 14 0.19
Perlitol 100SD
13.5 20 0.16
Perlitol 200SD
11.63 18 0.11
Perlitol 300DC
8.3 10 0.14
Perlitol 400DC
6.7 8 0.11
Perlitol 500DC
8.1 5 0.14
Galen IQ720
11.25 16 4.07
Galen IQ721
13.4 12 1.5
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck 0.1% 16.25 18 0.81
Parteck 1% 16.25 16 1.13
Parteck 10% 17.5 22 1.10
Perlitol 0.1% 11.25 12 0.96
Perlitol 1% 8.75 16 0.98
Perlitol 10% 16.25 18 1.32
Galen 0.1% 13.75 7 2.70
Galen 1% 16.25 8 2.65
Galen 10% 16.25 20 2.21
AN EVALUATION OF VARIOUS DIRECT COMPRESSION INGREDIENTS USING THE GAMLEN TABLET PRESS GTP-1
DIPANKAR DEY, MICHAEL GAMLEN, GAMLEN TABLETING LTD, BIOCITY NOTTINGHAM, NOTTINGHAM UK NG1 1GF
The modern tablet needs to satisfy a number of parameters that make it fit for purpose such as hardness, potency, friability and dissolution as well as be suitable for commercial manufacture using a rotary tablet press. Performing a sufficient number of experiments to optimise the formulation is often limited by the quantity of API available and the nature of the equipment used. We present here an approach to tablet formulation using a novel bench top computer controlled tablet press—the Gamlen Tablet Press GTP-1. This requires only milligram quantities of material, is objective and practical. The approach is based on establishing the compressibility of the formulation as determined by tablet tensile strength measurements using the diametral compression test (Fell &Newton) over a range of compression pressures ; Tensile strength is an objective measure of tablet strength as it takes into account both hardness and tablet thickness. As such it can be used to compare tablets of different shapes and sizes (Pitt &Heasley 2012). In addition we can also measure ejection stress associated with each formulation from the ejection force normalised with tablet thickness.
In the preliminary experiment the Galen IQ, Parteck SD and Perlitol SD grades were the most compressible whilst the Perlitol DC grades had the least. All formulations showed high ejection stress. We selected the 200 mesh size of each brand for further development with L-HPC21 in the Main experiments. The L-HPC21 substantially increased compressibility, and also reduced ejection stress and friability The drug percentage had a major effect in reducing compressibility particularly for the Galen IQ. Using The combination of results gained on compressibility combined with powder flow and ejection stress results give a useful screening method when selecting the formulation of choice. We assigned the gradient of the tensile strength v compression pressure profiles as the compressibility of the formulation. When plotted against the powder flowability for each formulation we can visualise the results as a ‘Decision Matrix’. The Galen 0.1%/1% + L-HPC21 exhibit the best combination of compressibility and flow behaviour. In this work we have shown that rapid screening of formulations using the Gamlen Tablet Press GTP-1 is a very useful approach to development of the required tablet profile using the compression gradient as a measure of compressibility. We propose that this be considered as a Critical Quality Attribute of a tablet formulation in the tablet Quality by Design paradigm.
The formulation was developed in two stages. Preliminary experiments determined the compressibility of a formulation containing the drug (acetaminophen), excipient and lubricant; ten excipients and excipient grades were evaluated on a 100g scale. In the main experiments we used the best formulations, selected using tensile fracture strength/compaction pressure profiles. To improve compressibility we added 20% L-HPC21 (Shin-Etsu). The magnesium stearate concentration was kept at 0.5%w/w. All formulations were made using the Gamlen Tablet Press GTP-1 (Nottingham UK) to produce 75mg round flat face tablets. The tablets were subjected to tensile fracture stress testing on the GTP-1, friability and disintegration measurements. Ejection stress was also recorded for each tablet.
Fell JT and Newton JM. Determination of tablet strength by the diametral compression test. J Pharm Sci 59; 688-691, 1970 Pitt & Heasley. Powder Technology 2012. http://dx.doi.org/10.1016/j.powtec.2011.12.060)
BACKGROUND AND APPROACH
APPROACH
MATERIALS AND METHODS
RESULTS
DISCUSSION AND CONCLUSION
REFERENCES
Preliminary Experiments
σt is the tensile fracture strength of the tablet, P is the fracture force (N), D is the tablet diameter, t is the overall thickness
Mannitol grade Parteck (Merck)
Mannitol grade Perlitol (Roquette)
Isomaltulose (Beneo-Palatinit)
Parteck M100
Perlitol 100SD
Galen IQ720
Parteck M200
Perlitol 200SD
Galen IQ721
Parteck M300
Perlitol 300DC
Perlitol 400DC
Perlitol 500DC
Main Experiments We have shown previously that the Gamlen Tablet Press GTP-1 can rapidly evaluate formulations for tablet development using milligram quantities of material. Uniquely for a tablet press it gives precise information on the compression force, ejection force and fracture force of an individual tablet, providing valuable information for the required target product profile, required for Quality by Design (QbD). We present in this work an evaluation of a number of different direct compression excipients in the development of a paracetamol tablet. We evaluated a number of different direct compression excipients to prepare a formulation containing 10% paracetamol. The formulations were blended for 30 minutes and lubricated with 0.5% magnesium stearate for a further 5 minutes in a blender. Each formulation was then compacted using the Gamlen Tablet Press GTP-1 to produce round flat face tablets. Tablets weresubjected to tensile strength, friability and disintegration testing, whilst the formulation was tested for flowability and LOD. The initial experiments showed clear differences between formulations in compressibility, friability, disintegration and powder flowability. Among the mannitol grades the compressibility of the SD types was better than the DC types. Very high ejection forces were recorded despite use of a lubricant. Individual ejection profiles analysed by the GTP-1 revealed the important relationship of material properties with ejection of the tablet from the die- a key determinant of suitability for rotary press manufacture. The main experiments characterised the compressibility and tablet behaviour of the most compressible excipients, with the low API% formulas performing best. Evaluation of a wide range of formulations using using the GTP-1 provided valuable information on compression force, ejection force and disintegration times of individual tablets using very small amounts of material. This enables an evaluation of the widest possible tablet quality and tablet/ material processing parameters to aid formulation development.
ABSTRACT
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck M100
14.5 16 0.27
Parteck M200
12.9 20 0.17
Parteck M300
7.4 14 0.19
Perlitol 100SD
13.5 20 0.16
Perlitol 200SD
11.63 18 0.11
Perlitol 300DC
8.3 10 0.14
Perlitol 400DC
6.7 8 0.11
Perlitol 500DC
8.1 5 0.14
Galen IQ720
11.25 16 4.07
Galen IQ721
13.4 12 1.5
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck 0.1% 16.25 18 0.81
Parteck 1% 16.25 16 1.13
Parteck 10% 17.5 22 1.10
Perlitol 0.1% 11.25 12 0.96
Perlitol 1% 8.75 16 0.98
Perlitol 10% 16.25 18 1.32
Galen 0.1% 13.75 7 2.70
Galen 1% 16.25 8 2.65
Galen 10% 16.25 20 2.21
AN EVALUATION OF VARIOUS DIRECT COMPRESSION INGREDIENTS USING THE GAMLEN TABLET PRESS GTP-1
DIPANKAR DEY, MICHAEL GAMLEN, GAMLEN TABLETING LTD, BIOCITY NOTTINGHAM, NOTTINGHAM UK NG1 1GF
The modern tablet needs to satisfy a number of parameters that make it fit for purpose such as hardness, potency, friability and dissolution as well as be suitable for commercial manufacture using a rotary tablet press. Performing a sufficient number of experiments to optimise the formulation is often limited by the quantity of API available and the nature of the equipment used. We present here an approach to tablet formulation using a novel bench top computer controlled tablet press—the Gamlen Tablet Press GTP-1. This requires only milligram quantities of material, is objective and practical. The approach is based on establishing the compressibility of the formulation as determined by tablet tensile strength measurements using the diametral compression test (Fell &Newton) over a range of compression pressures ; Tensile strength is an objective measure of tablet strength as it takes into account both hardness and tablet thickness. As such it can be used to compare tablets of different shapes and sizes (Pitt &Heasley 2012). In addition we can also measure ejection stress associated with each formulation from the ejection force normalised with tablet thickness.
In the preliminary experiment the Galen IQ, Parteck SD and Perlitol SD grades were the most compressible whilst the Perlitol DC grades had the least. All formulations showed high ejection stress. We selected the 200 mesh size of each brand for further development with L-HPC21 in the Main experiments. The L-HPC21 substantially increased compressibility, and also reduced ejection stress and friability The drug percentage had a major effect in reducing compressibility particularly for the Galen IQ. Using The combination of results gained on compressibility combined with powder flow and ejection stress results give a useful screening method when selecting the formulation of choice. We assigned the gradient of the tensile strength v compression pressure profiles as the compressibility of the formulation. When plotted against the powder flowability for each formulation we can visualise the results as a ‘Decision Matrix’. The Galen 0.1%/1% + L-HPC21 exhibit the best combination of compressibility and flow behaviour. In this work we have shown that rapid screening of formulations using the Gamlen Tablet Press GTP-1 is a very useful approach to development of the required tablet profile using the compression gradient as a measure of compressibility. We propose that this be considered as a Critical Quality Attribute of a tablet formulation in the tablet Quality by Design paradigm.
The formulation was developed in two stages. Preliminary experiments determined the compressibility of a formulation containing the drug (acetaminophen), excipient and lubricant; ten excipients and excipient grades were evaluated on a 100g scale. In the main experiments we used the best formulations, selected using tensile fracture strength/compaction pressure profiles. To improve compressibility we added 20% L-HPC21 (Shin-Etsu). The magnesium stearate concentration was kept at 0.5%w/w. All formulations were made using the Gamlen Tablet Press GTP-1 (Nottingham UK) to produce 75mg round flat face tablets. The tablets were subjected to tensile fracture stress testing on the GTP-1, friability and disintegration measurements. Ejection stress was also recorded for each tablet.
Fell JT and Newton JM. Determination of tablet strength by the diametral compression test. J Pharm Sci 59; 688-691, 1970 Pitt & Heasley. Powder Technology 2012. http://dx.doi.org/10.1016/j.powtec.2011.12.060)
BACKGROUND AND APPROACH
APPROACH
MATERIALS AND METHODS
RESULTS
DISCUSSION AND CONCLUSION
REFERENCES
Preliminary Experiments
σt is the tensile fracture strength of the tablet, P is the fracture force (N), D is the tablet diameter, t is the overall thickness
Mannitol grade Parteck (Merck)
Mannitol grade Perlitol (Roquette)
Isomaltulose (Beneo-Palatinit)
Parteck M100
Perlitol 100SD
Galen IQ720
Parteck M200
Perlitol 200SD
Galen IQ721
Parteck M300
Perlitol 300DC
Perlitol 400DC
Perlitol 500DC
Main Experiments We have shown previously that the Gamlen Tablet Press GTP-1 can rapidly evaluate formulations for tablet development using milligram quantities of material. Uniquely for a tablet press it gives precise information on the compression force, ejection force and fracture force of an individual tablet, providing valuable information for the required target product profile, required for Quality by Design (QbD). We present in this work an evaluation of a number of different direct compression excipients in the development of a paracetamol tablet. We evaluated a number of different direct compression excipients to prepare a formulation containing 10% paracetamol. The formulations were blended for 30 minutes and lubricated with 0.5% magnesium stearate for a further 5 minutes in a blender. Each formulation was then compacted using the Gamlen Tablet Press GTP-1 to produce round flat face tablets. Tablets weresubjected to tensile strength, friability and disintegration testing, whilst the formulation was tested for flowability and LOD. The initial experiments showed clear differences between formulations in compressibility, friability, disintegration and powder flowability. Among the mannitol grades the compressibility of the SD types was better than the DC types. Very high ejection forces were recorded despite use of a lubricant. Individual ejection profiles analysed by the GTP-1 revealed the important relationship of material properties with ejection of the tablet from the die- a key determinant of suitability for rotary press manufacture. The main experiments characterised the compressibility and tablet behaviour of the most compressible excipients, with the low API% formulas performing best. Evaluation of a wide range of formulations using using the GTP-1 provided valuable information on compression force, ejection force and disintegration times of individual tablets using very small amounts of material. This enables an evaluation of the widest possible tablet quality and tablet/ material processing parameters to aid formulation development.
ABSTRACT
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck M100
14.5 16 0.27
Parteck M200
12.9 20 0.17
Parteck M300
7.4 14 0.19
Perlitol 100SD
13.5 20 0.16
Perlitol 200SD
11.63 18 0.11
Perlitol 300DC
8.3 10 0.14
Perlitol 400DC
6.7 8 0.11
Perlitol 500DC
8.1 5 0.14
Galen IQ720
11.25 16 4.07
Galen IQ721
13.4 12 1.5
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck 0.1% 16.25 18 0.81
Parteck 1% 16.25 16 1.13
Parteck 10% 17.5 22 1.10
Perlitol 0.1% 11.25 12 0.96
Perlitol 1% 8.75 16 0.98
Perlitol 10% 16.25 18 1.32
Galen 0.1% 13.75 7 2.70
Galen 1% 16.25 8 2.65
Galen 10% 16.25 20 2.21
AN EVALUATION OF VARIOUS DIRECT COMPRESSION INGREDIENTS USING THE GAMLEN TABLET PRESS GTP-1
DIPANKAR DEY, MICHAEL GAMLEN, GAMLEN TABLETING LTD, BIOCITY NOTTINGHAM, NOTTINGHAM UK NG1 1GF
The modern tablet needs to satisfy a number of parameters that make it fit for purpose such as hardness, potency, friability and dissolution as well as be suitable for commercial manufacture using a rotary tablet press. Performing a sufficient number of experiments to optimise the formulation is often limited by the quantity of API available and the nature of the equipment used. We present here an approach to tablet formulation using a novel bench top computer controlled tablet press—the Gamlen Tablet Press GTP-1. This requires only milligram quantities of material, is objective and practical. The approach is based on establishing the compressibility of the formulation as determined by tablet tensile strength measurements using the diametral compression test (Fell &Newton) over a range of compression pressures ; Tensile strength is an objective measure of tablet strength as it takes into account both hardness and tablet thickness. As such it can be used to compare tablets of different shapes and sizes (Pitt &Heasley 2012). In addition we can also measure ejection stress associated with each formulation from the ejection force normalised with tablet thickness.
In the preliminary experiment the Galen IQ, Parteck SD and Perlitol SD grades were the most compressible whilst the Perlitol DC grades had the least. All formulations showed high ejection stress. We selected the 200 mesh size of each brand for further development with L-HPC21 in the Main experiments. The L-HPC21 substantially increased compressibility, and also reduced ejection stress and friability The drug percentage had a major effect in reducing compressibility particularly for the Galen IQ. Using The combination of results gained on compressibility combined with powder flow and ejection stress results give a useful screening method when selecting the formulation of choice. We assigned the gradient of the tensile strength v compression pressure profiles as the compressibility of the formulation. When plotted against the powder flowability for each formulation we can visualise the results as a ‘Decision Matrix’. The Galen 0.1%/1% + L-HPC21 exhibit the best combination of compressibility and flow behaviour. In this work we have shown that rapid screening of formulations using the Gamlen Tablet Press GTP-1 is a very useful approach to development of the required tablet profile using the compression gradient as a measure of compressibility. We propose that this be considered as a Critical Quality Attribute of a tablet formulation in the tablet Quality by Design paradigm.
The formulation was developed in two stages. Preliminary experiments determined the compressibility of a formulation containing the drug (acetaminophen), excipient and lubricant; ten excipients and excipient grades were evaluated on a 100g scale. In the main experiments we used the best formulations, selected using tensile fracture strength/compaction pressure profiles. To improve compressibility we added 20% L-HPC21 (Shin-Etsu). The magnesium stearate concentration was kept at 0.5%w/w. All formulations were made using the Gamlen Tablet Press GTP-1 (Nottingham UK) to produce 75mg round flat face tablets. The tablets were subjected to tensile fracture stress testing on the GTP-1, friability and disintegration measurements. Ejection stress was also recorded for each tablet.
Fell JT and Newton JM. Determination of tablet strength by the diametral compression test. J Pharm Sci 59; 688-691, 1970 Pitt & Heasley. Powder Technology 2012. http://dx.doi.org/10.1016/j.powtec.2011.12.060)
BACKGROUND AND APPROACH
APPROACH
MATERIALS AND METHODS
RESULTS
DISCUSSION AND CONCLUSION
REFERENCES
Preliminary Experiments
σt is the tensile fracture strength of the tablet, P is the fracture force (N), D is the tablet diameter, t is the overall thickness
Mannitol grade Parteck (Merck)
Mannitol grade Perlitol (Roquette)
Isomaltulose (Beneo-Palatinit)
Parteck M100
Perlitol 100SD
Galen IQ720
Parteck M200
Perlitol 200SD
Galen IQ721
Parteck M300
Perlitol 300DC
Perlitol 400DC
Perlitol 500DC
Main Experiments We have shown previously that the Gamlen Tablet Press GTP-1 can rapidly evaluate formulations for tablet development using milligram quantities of material. Uniquely for a tablet press it gives precise information on the compression force, ejection force and fracture force of an individual tablet, providing valuable information for the required target product profile, required for Quality by Design (QbD). We present in this work an evaluation of a number of different direct compression excipients in the development of a paracetamol tablet. We evaluated a number of different direct compression excipients to prepare a formulation containing 10% paracetamol. The formulations were blended for 30 minutes and lubricated with 0.5% magnesium stearate for a further 5 minutes in a blender. Each formulation was then compacted using the Gamlen Tablet Press GTP-1 to produce round flat face tablets. Tablets weresubjected to tensile strength, friability and disintegration testing, whilst the formulation was tested for flowability and LOD. The initial experiments showed clear differences between formulations in compressibility, friability, disintegration and powder flowability. Among the mannitol grades the compressibility of the SD types was better than the DC types. Very high ejection forces were recorded despite use of a lubricant. Individual ejection profiles analysed by the GTP-1 revealed the important relationship of material properties with ejection of the tablet from the die- a key determinant of suitability for rotary press manufacture. The main experiments characterised the compressibility and tablet behaviour of the most compressible excipients, with the low API% formulas performing best. Evaluation of a wide range of formulations using using the GTP-1 provided valuable information on compression force, ejection force and disintegration times of individual tablets using very small amounts of material. This enables an evaluation of the widest possible tablet quality and tablet/ material processing parameters to aid formulation development.
ABSTRACT
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck M100
14.5 16 0.27
Parteck M200
12.9 20 0.17
Parteck M300
7.4 14 0.19
Perlitol 100SD
13.5 20 0.16
Perlitol 200SD
11.63 18 0.11
Perlitol 300DC
8.3 10 0.14
Perlitol 400DC
6.7 8 0.11
Perlitol 500DC
8.1 5 0.14
Galen IQ720
11.25 16 4.07
Galen IQ721
13.4 12 1.5
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck 0.1% 16.25 18 0.81
Parteck 1% 16.25 16 1.13
Parteck 10% 17.5 22 1.10
Perlitol 0.1% 11.25 12 0.96
Perlitol 1% 8.75 16 0.98
Perlitol 10% 16.25 18 1.32
Galen 0.1% 13.75 7 2.70
Galen 1% 16.25 8 2.65
Galen 10% 16.25 20 2.21
AN EVALUATION OF VARIOUS DIRECT COMPRESSION INGREDIENTS USING THE GAMLEN TABLET PRESS GTP-1
DIPANKAR DEY, MICHAEL GAMLEN, GAMLEN TABLETING LTD, BIOCITY NOTTINGHAM, NOTTINGHAM UK NG1 1GF
The modern tablet needs to satisfy a number of parameters that make it fit for purpose such as hardness, potency, friability and dissolution as well as be suitable for commercial manufacture using a rotary tablet press. Performing a sufficient number of experiments to optimise the formulation is often limited by the quantity of API available and the nature of the equipment used. We present here an approach to tablet formulation using a novel bench top computer controlled tablet press—the Gamlen Tablet Press GTP-1. This requires only milligram quantities of material, is objective and practical. The approach is based on establishing the compressibility of the formulation as determined by tablet tensile strength measurements using the diametral compression test (Fell &Newton) over a range of compression pressures ; Tensile strength is an objective measure of tablet strength as it takes into account both hardness and tablet thickness. As such it can be used to compare tablets of different shapes and sizes (Pitt &Heasley 2012). In addition we can also measure ejection stress associated with each formulation from the ejection force normalised with tablet thickness.
In the preliminary experiment the Galen IQ, Parteck SD and Perlitol SD grades were the most compressible whilst the Perlitol DC grades had the least. All formulations showed high ejection stress. We selected the 200 mesh size of each brand for further development with L-HPC21 in the Main experiments. The L-HPC21 substantially increased compressibility, and also reduced ejection stress and friability The drug percentage had a major effect in reducing compressibility particularly for the Galen IQ. Using The combination of results gained on compressibility combined with powder flow and ejection stress results give a useful screening method when selecting the formulation of choice. We assigned the gradient of the tensile strength v compression pressure profiles as the compressibility of the formulation. When plotted against the powder flowability for each formulation we can visualise the results as a ‘Decision Matrix’. The Galen 0.1%/1% + L-HPC21 exhibit the best combination of compressibility and flow behaviour. In this work we have shown that rapid screening of formulations using the Gamlen Tablet Press GTP-1 is a very useful approach to development of the required tablet profile using the compression gradient as a measure of compressibility. We propose that this be considered as a Critical Quality Attribute of a tablet formulation in the tablet Quality by Design paradigm.
The formulation was developed in two stages. Preliminary experiments determined the compressibility of a formulation containing the drug (acetaminophen), excipient and lubricant; ten excipients and excipient grades were evaluated on a 100g scale. In the main experiments we used the best formulations, selected using tensile fracture strength/compaction pressure profiles. To improve compressibility we added 20% L-HPC21 (Shin-Etsu). The magnesium stearate concentration was kept at 0.5%w/w. All formulations were made using the Gamlen Tablet Press GTP-1 (Nottingham UK) to produce 75mg round flat face tablets. The tablets were subjected to tensile fracture stress testing on the GTP-1, friability and disintegration measurements. Ejection stress was also recorded for each tablet.
Fell JT and Newton JM. Determination of tablet strength by the diametral compression test. J Pharm Sci 59; 688-691, 1970 Pitt & Heasley. Powder Technology 2012. http://dx.doi.org/10.1016/j.powtec.2011.12.060)
BACKGROUND AND APPROACH
APPROACH
MATERIALS AND METHODS
RESULTS
DISCUSSION AND CONCLUSION
REFERENCES
Preliminary Experiments
σt is the tensile fracture strength of the tablet, P is the fracture force (N), D is the tablet diameter, t is the overall thickness
Mannitol grade Parteck (Merck)
Mannitol grade Perlitol (Roquette)
Isomaltulose (Beneo-Palatinit)
Parteck M100
Perlitol 100SD
Galen IQ720
Parteck M200
Perlitol 200SD
Galen IQ721
Parteck M300
Perlitol 300DC
Perlitol 400DC
Perlitol 500DC
Main Experiments We have shown previously that the Gamlen Tablet Press GTP-1 can rapidly evaluate formulations for tablet development using milligram quantities of material. Uniquely for a tablet press it gives precise information on the compression force, ejection force and fracture force of an individual tablet, providing valuable information for the required target product profile, required for Quality by Design (QbD). We present in this work an evaluation of a number of different direct compression excipients in the development of a paracetamol tablet. We evaluated a number of different direct compression excipients to prepare a formulation containing 10% paracetamol. The formulations were blended for 30 minutes and lubricated with 0.5% magnesium stearate for a further 5 minutes in a blender. Each formulation was then compacted using the Gamlen Tablet Press GTP-1 to produce round flat face tablets. Tablets weresubjected to tensile strength, friability and disintegration testing, whilst the formulation was tested for flowability and LOD. The initial experiments showed clear differences between formulations in compressibility, friability, disintegration and powder flowability. Among the mannitol grades the compressibility of the SD types was better than the DC types. Very high ejection forces were recorded despite use of a lubricant. Individual ejection profiles analysed by the GTP-1 revealed the important relationship of material properties with ejection of the tablet from the die- a key determinant of suitability for rotary press manufacture. The main experiments characterised the compressibility and tablet behaviour of the most compressible excipients, with the low API% formulas performing best. Evaluation of a wide range of formulations using using the GTP-1 provided valuable information on compression force, ejection force and disintegration times of individual tablets using very small amounts of material. This enables an evaluation of the widest possible tablet quality and tablet/ material processing parameters to aid formulation development.
ABSTRACT
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck M100
14.5 16 0.27
Parteck M200
12.9 20 0.17
Parteck M300
7.4 14 0.19
Perlitol 100SD
13.5 20 0.16
Perlitol 200SD
11.63 18 0.11
Perlitol 300DC
8.3 10 0.14
Perlitol 400DC
6.7 8 0.11
Perlitol 500DC
8.1 5 0.14
Galen IQ720
11.25 16 4.07
Galen IQ721
13.4 12 1.5
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck 0.1% 16.25 18 0.81
Parteck 1% 16.25 16 1.13
Parteck 10% 17.5 22 1.10
Perlitol 0.1% 11.25 12 0.96
Perlitol 1% 8.75 16 0.98
Perlitol 10% 16.25 18 1.32
Galen 0.1% 13.75 7 2.70
Galen 1% 16.25 8 2.65
Galen 10% 16.25 20 2.21
AN EVALUATION OF VARIOUS DIRECT COMPRESSION INGREDIENTS USING THE GAMLEN TABLET PRESS GTP-1
DIPANKAR DEY, MICHAEL GAMLEN, GAMLEN TABLETING LTD, BIOCITY NOTTINGHAM, NOTTINGHAM UK NG1 1GF
The modern tablet needs to satisfy a number of parameters that make it fit for purpose such as hardness, potency, friability and dissolution as well as be suitable for commercial manufacture using a rotary tablet press. Performing a sufficient number of experiments to optimise the formulation is often limited by the quantity of API available and the nature of the equipment used. We present here an approach to tablet formulation using a novel bench top computer controlled tablet press—the Gamlen Tablet Press GTP-1. This requires only milligram quantities of material, is objective and practical. The approach is based on establishing the compressibility of the formulation as determined by tablet tensile strength measurements using the diametral compression test (Fell &Newton) over a range of compression pressures ; Tensile strength is an objective measure of tablet strength as it takes into account both hardness and tablet thickness. As such it can be used to compare tablets of different shapes and sizes (Pitt &Heasley 2012). In addition we can also measure ejection stress associated with each formulation from the ejection force normalised with tablet thickness.
In the preliminary experiment the Galen IQ, Parteck SD and Perlitol SD grades were the most compressible whilst the Perlitol DC grades had the least. All formulations showed high ejection stress. We selected the 200 mesh size of each brand for further development with L-HPC21 in the Main experiments. The L-HPC21 substantially increased compressibility, and also reduced ejection stress and friability The drug percentage had a major effect in reducing compressibility particularly for the Galen IQ. Using The combination of results gained on compressibility combined with powder flow and ejection stress results give a useful screening method when selecting the formulation of choice. We assigned the gradient of the tensile strength v compression pressure profiles as the compressibility of the formulation. When plotted against the powder flowability for each formulation we can visualise the results as a ‘Decision Matrix’. The Galen 0.1%/1% + L-HPC21 exhibit the best combination of compressibility and flow behaviour. In this work we have shown that rapid screening of formulations using the Gamlen Tablet Press GTP-1 is a very useful approach to development of the required tablet profile using the compression gradient as a measure of compressibility. We propose that this be considered as a Critical Quality Attribute of a tablet formulation in the tablet Quality by Design paradigm.
The formulation was developed in two stages. Preliminary experiments determined the compressibility of a formulation containing the drug (acetaminophen), excipient and lubricant; ten excipients and excipient grades were evaluated on a 100g scale. In the main experiments we used the best formulations, selected using tensile fracture strength/compaction pressure profiles. To improve compressibility we added 20% L-HPC21 (Shin-Etsu). The magnesium stearate concentration was kept at 0.5%w/w. All formulations were made using the Gamlen Tablet Press GTP-1 (Nottingham UK) to produce 75mg round flat face tablets. The tablets were subjected to tensile fracture stress testing on the GTP-1, friability and disintegration measurements. Ejection stress was also recorded for each tablet.
Fell JT and Newton JM. Determination of tablet strength by the diametral compression test. J Pharm Sci 59; 688-691, 1970 Pitt & Heasley. Powder Technology 2012. http://dx.doi.org/10.1016/j.powtec.2011.12.060)
BACKGROUND AND APPROACH
APPROACH
MATERIALS AND METHODS
RESULTS
DISCUSSION AND CONCLUSION
REFERENCES
Preliminary Experiments
σt is the tensile fracture strength of the tablet, P is the fracture force (N), D is the tablet diameter, t is the overall thickness
Mannitol grade Parteck (Merck)
Mannitol grade Perlitol (Roquette)
Isomaltulose (Beneo-Palatinit)
Parteck M100
Perlitol 100SD
Galen IQ720
Parteck M200
Perlitol 200SD
Galen IQ721
Parteck M300
Perlitol 300DC
Perlitol 400DC
Perlitol 500DC
Main Experiments We have shown previously that the Gamlen Tablet Press GTP-1 can rapidly evaluate formulations for tablet development using milligram quantities of material. Uniquely for a tablet press it gives precise information on the compression force, ejection force and fracture force of an individual tablet, providing valuable information for the required target product profile, required for Quality by Design (QbD). We present in this work an evaluation of a number of different direct compression excipients in the development of a paracetamol tablet. We evaluated a number of different direct compression excipients to prepare a formulation containing 10% paracetamol. The formulations were blended for 30 minutes and lubricated with 0.5% magnesium stearate for a further 5 minutes in a blender. Each formulation was then compacted using the Gamlen Tablet Press GTP-1 to produce round flat face tablets. Tablets weresubjected to tensile strength, friability and disintegration testing, whilst the formulation was tested for flowability and LOD. The initial experiments showed clear differences between formulations in compressibility, friability, disintegration and powder flowability. Among the mannitol grades the compressibility of the SD types was better than the DC types. Very high ejection forces were recorded despite use of a lubricant. Individual ejection profiles analysed by the GTP-1 revealed the important relationship of material properties with ejection of the tablet from the die- a key determinant of suitability for rotary press manufacture. The main experiments characterised the compressibility and tablet behaviour of the most compressible excipients, with the low API% formulas performing best. Evaluation of a wide range of formulations using using the GTP-1 provided valuable information on compression force, ejection force and disintegration times of individual tablets using very small amounts of material. This enables an evaluation of the widest possible tablet quality and tablet/ material processing parameters to aid formulation development.
ABSTRACT
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck M100
14.5 16 0.27
Parteck M200
12.9 20 0.17
Parteck M300
7.4 14 0.19
Perlitol 100SD
13.5 20 0.16
Perlitol 200SD
11.63 18 0.11
Perlitol 300DC
8.3 10 0.14
Perlitol 400DC
6.7 8 0.11
Perlitol 500DC
8.1 5 0.14
Galen IQ720
11.25 16 4.07
Galen IQ721
13.4 12 1.5
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck 0.1% 16.25 18 0.81
Parteck 1% 16.25 16 1.13
Parteck 10% 17.5 22 1.10
Perlitol 0.1% 11.25 12 0.96
Perlitol 1% 8.75 16 0.98
Perlitol 10% 16.25 18 1.32
Galen 0.1% 13.75 7 2.70
Galen 1% 16.25 8 2.65
Galen 10% 16.25 20 2.21
AN EVALUATION OF VARIOUS DIRECT COMPRESSION INGREDIENTS USING THE GAMLEN TABLET PRESS GTP-1
DIPANKAR DEY, MICHAEL GAMLEN, GAMLEN TABLETING LTD, BIOCITY NOTTINGHAM, NOTTINGHAM UK NG1 1GF
The modern tablet needs to satisfy a number of parameters that make it fit for purpose such as hardness, potency, friability and dissolution as well as be suitable for commercial manufacture using a rotary tablet press. Performing a sufficient number of experiments to optimise the formulation is often limited by the quantity of API available and the nature of the equipment used. We present here an approach to tablet formulation using a novel bench top computer controlled tablet press—the Gamlen Tablet Press GTP-1. This requires only milligram quantities of material, is objective and practical. The approach is based on establishing the compressibility of the formulation as determined by tablet tensile strength measurements using the diametral compression test (Fell &Newton) over a range of compression pressures ; Tensile strength is an objective measure of tablet strength as it takes into account both hardness and tablet thickness. As such it can be used to compare tablets of different shapes and sizes (Pitt &Heasley 2012). In addition we can also measure ejection stress associated with each formulation from the ejection force normalised with tablet thickness.
In the preliminary experiment the Galen IQ, Parteck SD and Perlitol SD grades were the most compressible whilst the Perlitol DC grades had the least. All formulations showed high ejection stress. We selected the 200 mesh size of each brand for further development with L-HPC21 in the Main experiments. The L-HPC21 substantially increased compressibility, and also reduced ejection stress and friability The drug percentage had a major effect in reducing compressibility particularly for the Galen IQ. Using The combination of results gained on compressibility combined with powder flow and ejection stress results give a useful screening method when selecting the formulation of choice. We assigned the gradient of the tensile strength v compression pressure profiles as the compressibility of the formulation. When plotted against the powder flowability for each formulation we can visualise the results as a ‘Decision Matrix’. The Galen 0.1%/1% + L-HPC21 exhibit the best combination of compressibility and flow behaviour. In this work we have shown that rapid screening of formulations using the Gamlen Tablet Press GTP-1 is a very useful approach to development of the required tablet profile using the compression gradient as a measure of compressibility. We propose that this be considered as a Critical Quality Attribute of a tablet formulation in the tablet Quality by Design paradigm.
The formulation was developed in two stages. Preliminary experiments determined the compressibility of a formulation containing the drug (acetaminophen), excipient and lubricant; ten excipients and excipient grades were evaluated on a 100g scale. In the main experiments we used the best formulations, selected using tensile fracture strength/compaction pressure profiles. To improve compressibility we added 20% L-HPC21 (Shin-Etsu). The magnesium stearate concentration was kept at 0.5%w/w. All formulations were made using the Gamlen Tablet Press GTP-1 (Nottingham UK) to produce 75mg round flat face tablets. The tablets were subjected to tensile fracture stress testing on the GTP-1, friability and disintegration measurements. Ejection stress was also recorded for each tablet.
Fell JT and Newton JM. Determination of tablet strength by the diametral compression test. J Pharm Sci 59; 688-691, 1970 Pitt & Heasley. Powder Technology 2012. http://dx.doi.org/10.1016/j.powtec.2011.12.060)
BACKGROUND AND APPROACH
APPROACH
MATERIALS AND METHODS
RESULTS
DISCUSSION AND CONCLUSION
REFERENCES
Preliminary Experiments
σt is the tensile fracture strength of the tablet, P is the fracture force (N), D is the tablet diameter, t is the overall thickness
Mannitol grade Parteck (Merck)
Mannitol grade Perlitol (Roquette)
Isomaltulose (Beneo-Palatinit)
Parteck M100
Perlitol 100SD
Galen IQ720
Parteck M200
Perlitol 200SD
Galen IQ721
Parteck M300
Perlitol 300DC
Perlitol 400DC
Perlitol 500DC
Main Experiments We have shown previously that the Gamlen Tablet Press GTP-1 can rapidly evaluate formulations for tablet development using milligram quantities of material. Uniquely for a tablet press it gives precise information on the compression force, ejection force and fracture force of an individual tablet, providing valuable information for the required target product profile, required for Quality by Design (QbD). We present in this work an evaluation of a number of different direct compression excipients in the development of a paracetamol tablet. We evaluated a number of different direct compression excipients to prepare a formulation containing 10% paracetamol. The formulations were blended for 30 minutes and lubricated with 0.5% magnesium stearate for a further 5 minutes in a blender. Each formulation was then compacted using the Gamlen Tablet Press GTP-1 to produce round flat face tablets. Tablets weresubjected to tensile strength, friability and disintegration testing, whilst the formulation was tested for flowability and LOD. The initial experiments showed clear differences between formulations in compressibility, friability, disintegration and powder flowability. Among the mannitol grades the compressibility of the SD types was better than the DC types. Very high ejection forces were recorded despite use of a lubricant. Individual ejection profiles analysed by the GTP-1 revealed the important relationship of material properties with ejection of the tablet from the die- a key determinant of suitability for rotary press manufacture. The main experiments characterised the compressibility and tablet behaviour of the most compressible excipients, with the low API% formulas performing best. Evaluation of a wide range of formulations using using the GTP-1 provided valuable information on compression force, ejection force and disintegration times of individual tablets using very small amounts of material. This enables an evaluation of the widest possible tablet quality and tablet/ material processing parameters to aid formulation development.
ABSTRACT
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck M100
14.5 16 0.27
Parteck M200
12.9 20 0.17
Parteck M300
7.4 14 0.19
Perlitol 100SD
13.5 20 0.16
Perlitol 200SD
11.63 18 0.11
Perlitol 300DC
8.3 10 0.14
Perlitol 400DC
6.7 8 0.11
Perlitol 500DC
8.1 5 0.14
Galen IQ720
11.25 16 4.07
Galen IQ721
13.4 12 1.5
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck 0.1% 16.25 18 0.81
Parteck 1% 16.25 16 1.13
Parteck 10% 17.5 22 1.10
Perlitol 0.1% 11.25 12 0.96
Perlitol 1% 8.75 16 0.98
Perlitol 10% 16.25 18 1.32
Galen 0.1% 13.75 7 2.70
Galen 1% 16.25 8 2.65
Galen 10% 16.25 20 2.21
AN EVALUATION OF VARIOUS DIRECT COMPRESSION INGREDIENTS USING THE GAMLEN TABLET PRESS GTP-1
DIPANKAR DEY, MICHAEL GAMLEN, GAMLEN TABLETING LTD, BIOCITY NOTTINGHAM, NOTTINGHAM UK NG1 1GF
The modern tablet needs to satisfy a number of parameters that make it fit for purpose such as hardness, potency, friability and dissolution as well as be suitable for commercial manufacture using a rotary tablet press. Performing a sufficient number of experiments to optimise the formulation is often limited by the quantity of API available and the nature of the equipment used. We present here an approach to tablet formulation using a novel bench top computer controlled tablet press—the Gamlen Tablet Press GTP-1. This requires only milligram quantities of material, is objective and practical. The approach is based on establishing the compressibility of the formulation as determined by tablet tensile strength measurements using the diametral compression test (Fell &Newton) over a range of compression pressures ; Tensile strength is an objective measure of tablet strength as it takes into account both hardness and tablet thickness. As such it can be used to compare tablets of different shapes and sizes (Pitt &Heasley 2012). In addition we can also measure ejection stress associated with each formulation from the ejection force normalised with tablet thickness.
In the preliminary experiment the Galen IQ, Parteck SD and Perlitol SD grades were the most compressible whilst the Perlitol DC grades had the least. All formulations showed high ejection stress. We selected the 200 mesh size of each brand for further development with L-HPC21 in the Main experiments. The L-HPC21 substantially increased compressibility, and also reduced ejection stress and friability The drug percentage had a major effect in reducing compressibility particularly for the Galen IQ. Using The combination of results gained on compressibility combined with powder flow and ejection stress results give a useful screening method when selecting the formulation of choice. We assigned the gradient of the tensile strength v compression pressure profiles as the compressibility of the formulation. When plotted against the powder flowability for each formulation we can visualise the results as a ‘Decision Matrix’. The Galen 0.1%/1% + L-HPC21 exhibit the best combination of compressibility and flow behaviour. In this work we have shown that rapid screening of formulations using the Gamlen Tablet Press GTP-1 is a very useful approach to development of the required tablet profile using the compression gradient as a measure of compressibility. We propose that this be considered as a Critical Quality Attribute of a tablet formulation in the tablet Quality by Design paradigm.
The formulation was developed in two stages. Preliminary experiments determined the compressibility of a formulation containing the drug (acetaminophen), excipient and lubricant; ten excipients and excipient grades were evaluated on a 100g scale. In the main experiments we used the best formulations, selected using tensile fracture strength/compaction pressure profiles. To improve compressibility we added 20% L-HPC21 (Shin-Etsu). The magnesium stearate concentration was kept at 0.5%w/w. All formulations were made using the Gamlen Tablet Press GTP-1 (Nottingham UK) to produce 75mg round flat face tablets. The tablets were subjected to tensile fracture stress testing on the GTP-1, friability and disintegration measurements. Ejection stress was also recorded for each tablet.
Fell JT and Newton JM. Determination of tablet strength by the diametral compression test. J Pharm Sci 59; 688-691, 1970 Pitt & Heasley. Powder Technology 2012. http://dx.doi.org/10.1016/j.powtec.2011.12.060)
BACKGROUND AND APPROACH
APPROACH
MATERIALS AND METHODS
RESULTS
DISCUSSION AND CONCLUSION
REFERENCES
Preliminary Experiments
σt is the tensile fracture strength of the tablet, P is the fracture force (N), D is the tablet diameter, t is the overall thickness
Mannitol grade Parteck (Merck)
Mannitol grade Perlitol (Roquette)
Isomaltulose (Beneo-Palatinit)
Parteck M100
Perlitol 100SD
Galen IQ720
Parteck M200
Perlitol 200SD
Galen IQ721
Parteck M300
Perlitol 300DC
Perlitol 400DC
Perlitol 500DC
Main Experiments We have shown previously that the Gamlen Tablet Press GTP-1 can rapidly evaluate formulations for tablet development using milligram quantities of material. Uniquely for a tablet press it gives precise information on the compression force, ejection force and fracture force of an individual tablet, providing valuable information for the required target product profile, required for Quality by Design (QbD). We present in this work an evaluation of a number of different direct compression excipients in the development of a paracetamol tablet. We evaluated a number of different direct compression excipients to prepare a formulation containing 10% paracetamol. The formulations were blended for 30 minutes and lubricated with 0.5% magnesium stearate for a further 5 minutes in a blender. Each formulation was then compacted using the Gamlen Tablet Press GTP-1 to produce round flat face tablets. Tablets weresubjected to tensile strength, friability and disintegration testing, whilst the formulation was tested for flowability and LOD. The initial experiments showed clear differences between formulations in compressibility, friability, disintegration and powder flowability. Among the mannitol grades the compressibility of the SD types was better than the DC types. Very high ejection forces were recorded despite use of a lubricant. Individual ejection profiles analysed by the GTP-1 revealed the important relationship of material properties with ejection of the tablet from the die- a key determinant of suitability for rotary press manufacture. The main experiments characterised the compressibility and tablet behaviour of the most compressible excipients, with the low API% formulas performing best. Evaluation of a wide range of formulations using using the GTP-1 provided valuable information on compression force, ejection force and disintegration times of individual tablets using very small amounts of material. This enables an evaluation of the widest possible tablet quality and tablet/ material processing parameters to aid formulation development.
ABSTRACT
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck M100
14.5 16 0.27
Parteck M200
12.9 20 0.17
Parteck M300
7.4 14 0.19
Perlitol 100SD
13.5 20 0.16
Perlitol 200SD
11.63 18 0.11
Perlitol 300DC
8.3 10 0.14
Perlitol 400DC
6.7 8 0.11
Perlitol 500DC
8.1 5 0.14
Galen IQ720
11.25 16 4.07
Galen IQ721
13.4 12 1.5
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck 0.1% 16.25 18 0.81
Parteck 1% 16.25 16 1.13
Parteck 10% 17.5 22 1.10
Perlitol 0.1% 11.25 12 0.96
Perlitol 1% 8.75 16 0.98
Perlitol 10% 16.25 18 1.32
Galen 0.1% 13.75 7 2.70
Galen 1% 16.25 8 2.65
Galen 10% 16.25 20 2.21
AN EVALUATION OF VARIOUS DIRECT COMPRESSION INGREDIENTS USING THE GAMLEN TABLET PRESS GTP-1
DIPANKAR DEY, MICHAEL GAMLEN, GAMLEN TABLETING LTD, BIOCITY NOTTINGHAM, NOTTINGHAM UK NG1 1GF
The modern tablet needs to satisfy a number of parameters that make it fit for purpose such as hardness, potency, friability and dissolution as well as be suitable for commercial manufacture using a rotary tablet press. Performing a sufficient number of experiments to optimise the formulation is often limited by the quantity of API available and the nature of the equipment used. We present here an approach to tablet formulation using a novel bench top computer controlled tablet press—the Gamlen Tablet Press GTP-1. This requires only milligram quantities of material, is objective and practical. The approach is based on establishing the compressibility of the formulation as determined by tablet tensile strength measurements using the diametral compression test (Fell &Newton) over a range of compression pressures ; Tensile strength is an objective measure of tablet strength as it takes into account both hardness and tablet thickness. As such it can be used to compare tablets of different shapes and sizes (Pitt &Heasley 2012). In addition we can also measure ejection stress associated with each formulation from the ejection force normalised with tablet thickness.
In the preliminary experiment the Galen IQ, Parteck SD and Perlitol SD grades were the most compressible whilst the Perlitol DC grades had the least. All formulations showed high ejection stress. We selected the 200 mesh size of each brand for further development with L-HPC21 in the Main experiments. The L-HPC21 substantially increased compressibility, and also reduced ejection stress and friability The drug percentage had a major effect in reducing compressibility particularly for the Galen IQ. Using The combination of results gained on compressibility combined with powder flow and ejection stress results give a useful screening method when selecting the formulation of choice. We assigned the gradient of the tensile strength v compression pressure profiles as the compressibility of the formulation. When plotted against the powder flowability for each formulation we can visualise the results as a ‘Decision Matrix’. The Galen 0.1%/1% + L-HPC21 exhibit the best combination of compressibility and flow behaviour. In this work we have shown that rapid screening of formulations using the Gamlen Tablet Press GTP-1 is a very useful approach to development of the required tablet profile using the compression gradient as a measure of compressibility. We propose that this be considered as a Critical Quality Attribute of a tablet formulation in the tablet Quality by Design paradigm.
The formulation was developed in two stages. Preliminary experiments determined the compressibility of a formulation containing the drug (acetaminophen), excipient and lubricant; ten excipients and excipient grades were evaluated on a 100g scale. In the main experiments we used the best formulations, selected using tensile fracture strength/compaction pressure profiles. To improve compressibility we added 20% L-HPC21 (Shin-Etsu). The magnesium stearate concentration was kept at 0.5%w/w. All formulations were made using the Gamlen Tablet Press GTP-1 (Nottingham UK) to produce 75mg round flat face tablets. The tablets were subjected to tensile fracture stress testing on the GTP-1, friability and disintegration measurements. Ejection stress was also recorded for each tablet.
Fell JT and Newton JM. Determination of tablet strength by the diametral compression test. J Pharm Sci 59; 688-691, 1970 Pitt & Heasley. Powder Technology 2012. http://dx.doi.org/10.1016/j.powtec.2011.12.060)
BACKGROUND AND APPROACH
APPROACH
MATERIALS AND METHODS
RESULTS
DISCUSSION AND CONCLUSION
REFERENCES
Preliminary Experiments
σt is the tensile fracture strength of the tablet, P is the fracture force (N), D is the tablet diameter, t is the overall thickness
Mannitol grade Parteck (Merck)
Mannitol grade Perlitol (Roquette)
Isomaltulose (Beneo-Palatinit)
Parteck M100
Perlitol 100SD
Galen IQ720
Parteck M200
Perlitol 200SD
Galen IQ721
Parteck M300
Perlitol 300DC
Perlitol 400DC
Perlitol 500DC
Main Experiments We have shown previously that the Gamlen Tablet Press GTP-1 can rapidly evaluate formulations for tablet development using milligram quantities of material. Uniquely for a tablet press it gives precise information on the compression force, ejection force and fracture force of an individual tablet, providing valuable information for the required target product profile, required for Quality by Design (QbD). We present in this work an evaluation of a number of different direct compression excipients in the development of a paracetamol tablet. We evaluated a number of different direct compression excipients to prepare a formulation containing 10% paracetamol. The formulations were blended for 30 minutes and lubricated with 0.5% magnesium stearate for a further 5 minutes in a blender. Each formulation was then compacted using the Gamlen Tablet Press GTP-1 to produce round flat face tablets. Tablets weresubjected to tensile strength, friability and disintegration testing, whilst the formulation was tested for flowability and LOD. The initial experiments showed clear differences between formulations in compressibility, friability, disintegration and powder flowability. Among the mannitol grades the compressibility of the SD types was better than the DC types. Very high ejection forces were recorded despite use of a lubricant. Individual ejection profiles analysed by the GTP-1 revealed the important relationship of material properties with ejection of the tablet from the die- a key determinant of suitability for rotary press manufacture. The main experiments characterised the compressibility and tablet behaviour of the most compressible excipients, with the low API% formulas performing best. Evaluation of a wide range of formulations using using the GTP-1 provided valuable information on compression force, ejection force and disintegration times of individual tablets using very small amounts of material. This enables an evaluation of the widest possible tablet quality and tablet/ material processing parameters to aid formulation development.
ABSTRACT
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck M100
14.5 16 0.27
Parteck M200
12.9 20 0.17
Parteck M300
7.4 14 0.19
Perlitol 100SD
13.5 20 0.16
Perlitol 200SD
11.63 18 0.11
Perlitol 300DC
8.3 10 0.14
Perlitol 400DC
6.7 8 0.11
Perlitol 500DC
8.1 5 0.14
Galen IQ720
11.25 16 4.07
Galen IQ721
13.4 12 1.5
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck 0.1% 16.25 18 0.81
Parteck 1% 16.25 16 1.13
Parteck 10% 17.5 22 1.10
Perlitol 0.1% 11.25 12 0.96
Perlitol 1% 8.75 16 0.98
Perlitol 10% 16.25 18 1.32
Galen 0.1% 13.75 7 2.70
Galen 1% 16.25 8 2.65
Galen 10% 16.25 20 2.21
AN EVALUATION OF VARIOUS DIRECT COMPRESSION INGREDIENTS USING THE GAMLEN TABLET PRESS GTP-1
DIPANKAR DEY, MICHAEL GAMLEN, GAMLEN TABLETING LTD, BIOCITY NOTTINGHAM, NOTTINGHAM UK NG1 1GF
The modern tablet needs to satisfy a number of parameters that make it fit for purpose such as hardness, potency, friability and dissolution as well as be suitable for commercial manufacture using a rotary tablet press. Performing a sufficient number of experiments to optimise the formulation is often limited by the quantity of API available and the nature of the equipment used. We present here an approach to tablet formulation using a novel bench top computer controlled tablet press—the Gamlen Tablet Press GTP-1. This requires only milligram quantities of material, is objective and practical. The approach is based on establishing the compressibility of the formulation as determined by tablet tensile strength measurements using the diametral compression test (Fell &Newton) over a range of compression pressures ; Tensile strength is an objective measure of tablet strength as it takes into account both hardness and tablet thickness. As such it can be used to compare tablets of different shapes and sizes (Pitt &Heasley 2012). In addition we can also measure ejection stress associated with each formulation from the ejection force normalised with tablet thickness.
In the preliminary experiment the Galen IQ, Parteck SD and Perlitol SD grades were the most compressible whilst the Perlitol DC grades had the least. All formulations showed high ejection stress. We selected the 200 mesh size of each brand for further development with L-HPC21 in the Main experiments. The L-HPC21 substantially increased compressibility, and also reduced ejection stress and friability The drug percentage had a major effect in reducing compressibility particularly for the Galen IQ. Using The combination of results gained on compressibility combined with powder flow and ejection stress results give a useful screening method when selecting the formulation of choice. We assigned the gradient of the tensile strength v compression pressure profiles as the compressibility of the formulation. When plotted against the powder flowability for each formulation we can visualise the results as a ‘Decision Matrix’. The Galen 0.1%/1% + L-HPC21 exhibit the best combination of compressibility and flow behaviour. In this work we have shown that rapid screening of formulations using the Gamlen Tablet Press GTP-1 is a very useful approach to development of the required tablet profile using the compression gradient as a measure of compressibility. We propose that this be considered as a Critical Quality Attribute of a tablet formulation in the tablet Quality by Design paradigm.
The formulation was developed in two stages. Preliminary experiments determined the compressibility of a formulation containing the drug (acetaminophen), excipient and lubricant; ten excipients and excipient grades were evaluated on a 100g scale. In the main experiments we used the best formulations, selected using tensile fracture strength/compaction pressure profiles. To improve compressibility we added 20% L-HPC21 (Shin-Etsu). The magnesium stearate concentration was kept at 0.5%w/w. All formulations were made using the Gamlen Tablet Press GTP-1 (Nottingham UK) to produce 75mg round flat face tablets. The tablets were subjected to tensile fracture stress testing on the GTP-1, friability and disintegration measurements. Ejection stress was also recorded for each tablet.
Fell JT and Newton JM. Determination of tablet strength by the diametral compression test. J Pharm Sci 59; 688-691, 1970 Pitt & Heasley. Powder Technology 2012. http://dx.doi.org/10.1016/j.powtec.2011.12.060)
BACKGROUND AND APPROACH
APPROACH
MATERIALS AND METHODS
RESULTS
DISCUSSION AND CONCLUSION
REFERENCES
Preliminary Experiments
σt is the tensile fracture strength of the tablet, P is the fracture force (N), D is the tablet diameter, t is the overall thickness
Mannitol grade Parteck (Merck)
Mannitol grade Perlitol (Roquette)
Isomaltulose (Beneo-Palatinit)
Parteck M100
Perlitol 100SD
Galen IQ720
Parteck M200
Perlitol 200SD
Galen IQ721
Parteck M300
Perlitol 300DC
Perlitol 400DC
Perlitol 500DC
Main Experiments We have shown previously that the Gamlen Tablet Press GTP-1 can rapidly evaluate formulations for tablet development using milligram quantities of material. Uniquely for a tablet press it gives precise information on the compression force, ejection force and fracture force of an individual tablet, providing valuable information for the required target product profile, required for Quality by Design (QbD). We present in this work an evaluation of a number of different direct compression excipients in the development of a paracetamol tablet. We evaluated a number of different direct compression excipients to prepare a formulation containing 10% paracetamol. The formulations were blended for 30 minutes and lubricated with 0.5% magnesium stearate for a further 5 minutes in a blender. Each formulation was then compacted using the Gamlen Tablet Press GTP-1 to produce round flat face tablets. Tablets weresubjected to tensile strength, friability and disintegration testing, whilst the formulation was tested for flowability and LOD. The initial experiments showed clear differences between formulations in compressibility, friability, disintegration and powder flowability. Among the mannitol grades the compressibility of the SD types was better than the DC types. Very high ejection forces were recorded despite use of a lubricant. Individual ejection profiles analysed by the GTP-1 revealed the important relationship of material properties with ejection of the tablet from the die- a key determinant of suitability for rotary press manufacture. The main experiments characterised the compressibility and tablet behaviour of the most compressible excipients, with the low API% formulas performing best. Evaluation of a wide range of formulations using using the GTP-1 provided valuable information on compression force, ejection force and disintegration times of individual tablets using very small amounts of material. This enables an evaluation of the widest possible tablet quality and tablet/ material processing parameters to aid formulation development.
ABSTRACT
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck M100
14.5 16 0.27
Parteck M200
12.9 20 0.17
Parteck M300
7.4 14 0.19
Perlitol 100SD
13.5 20 0.16
Perlitol 200SD
11.63 18 0.11
Perlitol 300DC
8.3 10 0.14
Perlitol 400DC
6.7 8 0.11
Perlitol 500DC
8.1 5 0.14
Galen IQ720
11.25 16 4.07
Galen IQ721
13.4 12 1.5
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck 0.1% 16.25 18 0.81
Parteck 1% 16.25 16 1.13
Parteck 10% 17.5 22 1.10
Perlitol 0.1% 11.25 12 0.96
Perlitol 1% 8.75 16 0.98
Perlitol 10% 16.25 18 1.32
Galen 0.1% 13.75 7 2.70
Galen 1% 16.25 8 2.65
Galen 10% 16.25 20 2.21
AN EVALUATION OF VARIOUS DIRECT COMPRESSION INGREDIENTS USING THE GAMLEN TABLET PRESS GTP-1
DIPANKAR DEY, MICHAEL GAMLEN, GAMLEN TABLETING LTD, BIOCITY NOTTINGHAM, NOTTINGHAM UK NG1 1GF
The modern tablet needs to satisfy a number of parameters that make it fit for purpose such as hardness, potency, friability and dissolution as well as be suitable for commercial manufacture using a rotary tablet press. Performing a sufficient number of experiments to optimise the formulation is often limited by the quantity of API available and the nature of the equipment used. We present here an approach to tablet formulation using a novel bench top computer controlled tablet press—the Gamlen Tablet Press GTP-1. This requires only milligram quantities of material, is objective and practical. The approach is based on establishing the compressibility of the formulation as determined by tablet tensile strength measurements using the diametral compression test (Fell &Newton) over a range of compression pressures ; Tensile strength is an objective measure of tablet strength as it takes into account both hardness and tablet thickness. As such it can be used to compare tablets of different shapes and sizes (Pitt &Heasley 2012). In addition we can also measure ejection stress associated with each formulation from the ejection force normalised with tablet thickness.
In the preliminary experiment the Galen IQ, Parteck SD and Perlitol SD grades were the most compressible whilst the Perlitol DC grades had the least. All formulations showed high ejection stress. We selected the 200 mesh size of each brand for further development with L-HPC21 in the Main experiments. The L-HPC21 substantially increased compressibility, and also reduced ejection stress and friability The drug percentage had a major effect in reducing compressibility particularly for the Galen IQ. Using The combination of results gained on compressibility combined with powder flow and ejection stress results give a useful screening method when selecting the formulation of choice. We assigned the gradient of the tensile strength v compression pressure profiles as the compressibility of the formulation. When plotted against the powder flowability for each formulation we can visualise the results as a ‘Decision Matrix’. The Galen 0.1%/1% + L-HPC21 exhibit the best combination of compressibility and flow behaviour. In this work we have shown that rapid screening of formulations using the Gamlen Tablet Press GTP-1 is a very useful approach to development of the required tablet profile using the compression gradient as a measure of compressibility. We propose that this be considered as a Critical Quality Attribute of a tablet formulation in the tablet Quality by Design paradigm.
The formulation was developed in two stages. Preliminary experiments determined the compressibility of a formulation containing the drug (acetaminophen), excipient and lubricant; ten excipients and excipient grades were evaluated on a 100g scale. In the main experiments we used the best formulations, selected using tensile fracture strength/compaction pressure profiles. To improve compressibility we added 20% L-HPC21 (Shin-Etsu). The magnesium stearate concentration was kept at 0.5%w/w. All formulations were made using the Gamlen Tablet Press GTP-1 (Nottingham UK) to produce 75mg round flat face tablets. The tablets were subjected to tensile fracture stress testing on the GTP-1, friability and disintegration measurements. Ejection stress was also recorded for each tablet.
Fell JT and Newton JM. Determination of tablet strength by the diametral compression test. J Pharm Sci 59; 688-691, 1970 Pitt & Heasley. Powder Technology 2012. http://dx.doi.org/10.1016/j.powtec.2011.12.060)
BACKGROUND AND APPROACH
APPROACH
MATERIALS AND METHODS
RESULTS
DISCUSSION AND CONCLUSION
REFERENCES
Preliminary Experiments
σt is the tensile fracture strength of the tablet, P is the fracture force (N), D is the tablet diameter, t is the overall thickness
Mannitol grade Parteck (Merck)
Mannitol grade Perlitol (Roquette)
Isomaltulose (Beneo-Palatinit)
Parteck M100
Perlitol 100SD
Galen IQ720
Parteck M200
Perlitol 200SD
Galen IQ721
Parteck M300
Perlitol 300DC
Perlitol 400DC
Perlitol 500DC
Main Experiments We have shown previously that the Gamlen Tablet Press GTP-1 can rapidly evaluate formulations for tablet development using milligram quantities of material. Uniquely for a tablet press it gives precise information on the compression force, ejection force and fracture force of an individual tablet, providing valuable information for the required target product profile, required for Quality by Design (QbD). We present in this work an evaluation of a number of different direct compression excipients in the development of a paracetamol tablet. We evaluated a number of different direct compression excipients to prepare a formulation containing 10% paracetamol. The formulations were blended for 30 minutes and lubricated with 0.5% magnesium stearate for a further 5 minutes in a blender. Each formulation was then compacted using the Gamlen Tablet Press GTP-1 to produce round flat face tablets. Tablets weresubjected to tensile strength, friability and disintegration testing, whilst the formulation was tested for flowability and LOD. The initial experiments showed clear differences between formulations in compressibility, friability, disintegration and powder flowability. Among the mannitol grades the compressibility of the SD types was better than the DC types. Very high ejection forces were recorded despite use of a lubricant. Individual ejection profiles analysed by the GTP-1 revealed the important relationship of material properties with ejection of the tablet from the die- a key determinant of suitability for rotary press manufacture. The main experiments characterised the compressibility and tablet behaviour of the most compressible excipients, with the low API% formulas performing best. Evaluation of a wide range of formulations using using the GTP-1 provided valuable information on compression force, ejection force and disintegration times of individual tablets using very small amounts of material. This enables an evaluation of the widest possible tablet quality and tablet/ material processing parameters to aid formulation development.
ABSTRACT
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck M100
14.5 16 0.27
Parteck M200
12.9 20 0.17
Parteck M300
7.4 14 0.19
Perlitol 100SD
13.5 20 0.16
Perlitol 200SD
11.63 18 0.11
Perlitol 300DC
8.3 10 0.14
Perlitol 400DC
6.7 8 0.11
Perlitol 500DC
8.1 5 0.14
Galen IQ720
11.25 16 4.07
Galen IQ721
13.4 12 1.5
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck 0.1% 16.25 18 0.81
Parteck 1% 16.25 16 1.13
Parteck 10% 17.5 22 1.10
Perlitol 0.1% 11.25 12 0.96
Perlitol 1% 8.75 16 0.98
Perlitol 10% 16.25 18 1.32
Galen 0.1% 13.75 7 2.70
Galen 1% 16.25 8 2.65
Galen 10% 16.25 20 2.21
AN EVALUATION OF VARIOUS DIRECT COMPRESSION INGREDIENTS USING THE GAMLEN TABLET PRESS GTP-1
DIPANKAR DEY, MICHAEL GAMLEN, GAMLEN TABLETING LTD, BIOCITY NOTTINGHAM, NOTTINGHAM UK NG1 1GF
The modern tablet needs to satisfy a number of parameters that make it fit for purpose such as hardness, potency, friability and dissolution as well as be suitable for commercial manufacture using a rotary tablet press. Performing a sufficient number of experiments to optimise the formulation is often limited by the quantity of API available and the nature of the equipment used. We present here an approach to tablet formulation using a novel bench top computer controlled tablet press—the Gamlen Tablet Press GTP-1. This requires only milligram quantities of material, is objective and practical. The approach is based on establishing the compressibility of the formulation as determined by tablet tensile strength measurements using the diametral compression test (Fell &Newton) over a range of compression pressures ; Tensile strength is an objective measure of tablet strength as it takes into account both hardness and tablet thickness. As such it can be used to compare tablets of different shapes and sizes (Pitt &Heasley 2012). In addition we can also measure ejection stress associated with each formulation from the ejection force normalised with tablet thickness.
In the preliminary experiment the Galen IQ, Parteck SD and Perlitol SD grades were the most compressible whilst the Perlitol DC grades had the least. All formulations showed high ejection stress. We selected the 200 mesh size of each brand for further development with L-HPC21 in the Main experiments. The L-HPC21 substantially increased compressibility, and also reduced ejection stress and friability The drug percentage had a major effect in reducing compressibility particularly for the Galen IQ. Using The combination of results gained on compressibility combined with powder flow and ejection stress results give a useful screening method when selecting the formulation of choice. We assigned the gradient of the tensile strength v compression pressure profiles as the compressibility of the formulation. When plotted against the powder flowability for each formulation we can visualise the results as a ‘Decision Matrix’. The Galen 0.1%/1% + L-HPC21 exhibit the best combination of compressibility and flow behaviour. In this work we have shown that rapid screening of formulations using the Gamlen Tablet Press GTP-1 is a very useful approach to development of the required tablet profile using the compression gradient as a measure of compressibility. We propose that this be considered as a Critical Quality Attribute of a tablet formulation in the tablet Quality by Design paradigm.
The formulation was developed in two stages. Preliminary experiments determined the compressibility of a formulation containing the drug (acetaminophen), excipient and lubricant; ten excipients and excipient grades were evaluated on a 100g scale. In the main experiments we used the best formulations, selected using tensile fracture strength/compaction pressure profiles. To improve compressibility we added 20% L-HPC21 (Shin-Etsu). The magnesium stearate concentration was kept at 0.5%w/w. All formulations were made using the Gamlen Tablet Press GTP-1 (Nottingham UK) to produce 75mg round flat face tablets. The tablets were subjected to tensile fracture stress testing on the GTP-1, friability and disintegration measurements. Ejection stress was also recorded for each tablet.
Fell JT and Newton JM. Determination of tablet strength by the diametral compression test. J Pharm Sci 59; 688-691, 1970 Pitt & Heasley. Powder Technology 2012. http://dx.doi.org/10.1016/j.powtec.2011.12.060)
BACKGROUND AND APPROACH
APPROACH
MATERIALS AND METHODS
RESULTS
DISCUSSION AND CONCLUSION
REFERENCES
Preliminary Experiments
σt is the tensile fracture strength of the tablet, P is the fracture force (N), D is the tablet diameter, t is the overall thickness
Mannitol grade Parteck (Merck)
Mannitol grade Perlitol (Roquette)
Isomaltulose (Beneo-Palatinit)
Parteck M100
Perlitol 100SD
Galen IQ720
Parteck M200
Perlitol 200SD
Galen IQ721
Parteck M300
Perlitol 300DC
Perlitol 400DC
Perlitol 500DC
Main Experiments We have shown previously that the Gamlen Tablet Press GTP-1 can rapidly evaluate formulations for tablet development using milligram quantities of material. Uniquely for a tablet press it gives precise information on the compression force, ejection force and fracture force of an individual tablet, providing valuable information for the required target product profile, required for Quality by Design (QbD). We present in this work an evaluation of a number of different direct compression excipients in the development of a paracetamol tablet. We evaluated a number of different direct compression excipients to prepare a formulation containing 10% paracetamol. The formulations were blended for 30 minutes and lubricated with 0.5% magnesium stearate for a further 5 minutes in a blender. Each formulation was then compacted using the Gamlen Tablet Press GTP-1 to produce round flat face tablets. Tablets weresubjected to tensile strength, friability and disintegration testing, whilst the formulation was tested for flowability and LOD. The initial experiments showed clear differences between formulations in compressibility, friability, disintegration and powder flowability. Among the mannitol grades the compressibility of the SD types was better than the DC types. Very high ejection forces were recorded despite use of a lubricant. Individual ejection profiles analysed by the GTP-1 revealed the important relationship of material properties with ejection of the tablet from the die- a key determinant of suitability for rotary press manufacture. The main experiments characterised the compressibility and tablet behaviour of the most compressible excipients, with the low API% formulas performing best. Evaluation of a wide range of formulations using using the GTP-1 provided valuable information on compression force, ejection force and disintegration times of individual tablets using very small amounts of material. This enables an evaluation of the widest possible tablet quality and tablet/ material processing parameters to aid formulation development.
ABSTRACT
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck M100
14.5 16 0.27
Parteck M200
12.9 20 0.17
Parteck M300
7.4 14 0.19
Perlitol 100SD
13.5 20 0.16
Perlitol 200SD
11.63 18 0.11
Perlitol 300DC
8.3 10 0.14
Perlitol 400DC
6.7 8 0.11
Perlitol 500DC
8.1 5 0.14
Galen IQ720
11.25 16 4.07
Galen IQ721
13.4 12 1.5
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck 0.1% 16.25 18 0.81
Parteck 1% 16.25 16 1.13
Parteck 10% 17.5 22 1.10
Perlitol 0.1% 11.25 12 0.96
Perlitol 1% 8.75 16 0.98
Perlitol 10% 16.25 18 1.32
Galen 0.1% 13.75 7 2.70
Galen 1% 16.25 8 2.65
Galen 10% 16.25 20 2.21
DISCUSSION AND CONCLUSION
In the preliminary experiment the Galen IQ, Parteck SD and Perlitol SD grades were the most compressible whilst the Perlitol DC grades had the least. All formulations showed high ejection stress. We selected the 200 mesh size of each brand for further development with L-HPC21 in the Main experiments.
The L-HPC21 substantially increased compressibility, and also reduced ejection stress and friability The drug percentage had a major effect in reducing compressibility particularly for the Galen IQ. Using The combination of results gained on compressibility combined with powder flow and ejection stress results give a useful screening method when selecting the formulation of choice. We assigned the gradient of the tensile strength v compression pressure profiles as the compressibility of the formulation. When plotted against the powder flowability for each formulation we can visualise the results as a ‘Decision Matrix’. The Galen 0.1%/1% + L-HPC21 exhibit the best combination of compressibility and flow behaviour.
In this work we have shown that rapid screening of formulations using the Gamlen Tablet Press GTP-1 is a very useful approach to development of the required tablet profile using the compression gradient as a measure of compressibility. We propose that this be considered as a Critical Quality Attribute of a tablet formulation in the tablet Quality by Design paradigm.
Preliminary Experiments
Main Experiments
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck M100 14.5 16 0.27
Parteck M200 12.9 20 0.17
Parteck M300 7.4 14 0.19
Perlitol 100SD 13.5 20 0.16
Perlitol 200SD 11.63 18 0.11
Perlitol 300DC 8.3 10 0.14
Perlitol 400DC 6.7 8 0.11
Perlitol 500DC 8.1 5 0.14
Galen IQ720 11.25 16 4.07
Galen IQ721 13.4 12 1.5
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck 0.1% 16.25 18 0.81
Parteck 1% 16.25 16 1.13
Parteck 10% 17.5 22 1.10
Perlitol 0.1% 11.25 12 0.96
Perlitol 1% 8.75 16 0.98
Perlitol 10% 16.25 18 1.32
Galen 0.1% 13.75 7 2.70
Galen 1% 16.25 8 0.14
Galen 10% 16.25 20 2.21
AN EVALUATION OF VARIOUS DIRECT COMPRESSION INGREDIENTS USING THE GAMLEN TABLET PRESS GTP-1
DIPANKAR DEY, MICHAEL GAMLEN, GAMLEN TABLETING LTD, BIOCITY NOTTINGHAM, NOTTINGHAM UK NG1 1GF
The modern tablet needs to satisfy a number of parameters that make it fit for purpose such as hardness, potency, friability and dissolution as well as be suitable for commercial manufacture using a rotary tablet press. Performing a sufficient number of experiments to optimise the formulation is often limited by the quantity of API available and the nature of the equipment used. We present here an approach to tablet formulation using a novel bench top computer controlled tablet press—the Gamlen Tablet Press GTP-1. This requires only milligram quantities of material, is objective and practical. The approach is based on establishing the compressibility of the formulation as determined by tablet tensile strength measurements using the diametral compression test (Fell &Newton) over a range of compression pressures ; Tensile strength is an objective measure of tablet strength as it takes into account both hardness and tablet thickness. As such it can be used to compare tablets of different shapes and sizes (Pitt &Heasley 2012). In addition we can also measure ejection stress associated with each formulation from the ejection force normalised with tablet thickness.
In the preliminary experiment the Galen IQ, Parteck SD and Perlitol SD grades were the most compressible whilst the Perlitol DC grades had the least. All formulations showed high ejection stress. We selected the 200 mesh size of each brand for further development with L-HPC21 in the Main experiments. The L-HPC21 substantially increased compressibility, and also reduced ejection stress and friability The drug percentage had a major effect in reducing compressibility particularly for the Galen IQ. Using The combination of results gained on compressibility combined with powder flow and ejection stress results give a useful screening method when selecting the formulation of choice. We assigned the gradient of the tensile strength v compression pressure profiles as the compressibility of the formulation. When plotted against the powder flowability for each formulation we can visualise the results as a ‘Decision Matrix’. The Galen 0.1%/1% + L-HPC21 exhibit the best combination of compressibility and flow behaviour. In this work we have shown that rapid screening of formulations using the Gamlen Tablet Press GTP-1 is a very useful approach to development of the required tablet profile using the compression gradient as a measure of compressibility. We propose that this be considered as a Critical Quality Attribute of a tablet formulation in the tablet Quality by Design paradigm.
The formulation was developed in two stages. Preliminary experiments determined the compressibility of a formulation containing the drug (acetaminophen), excipient and lubricant; ten excipients and excipient grades were evaluated on a 100g scale. In the main experiments we used the best formulations, selected using tensile fracture strength/compaction pressure profiles. To improve compressibility we added 20% L-HPC21 (Shin-Etsu). The magnesium stearate concentration was kept at 0.5%w/w. All formulations were made using the Gamlen Tablet Press GTP-1 (Nottingham UK) to produce 75mg round flat face tablets. The tablets were subjected to tensile fracture stress testing on the GTP-1, friability and disintegration measurements. Ejection stress was also recorded for each tablet.
Fell JT and Newton JM. Determination of tablet strength by the diametral compression test. J Pharm Sci 59; 688-691, 1970 Pitt & Heasley. Powder Technology 2012. http://dx.doi.org/10.1016/j.powtec.2011.12.060)
BACKGROUND AND APPROACH
APPROACH
MATERIALS AND METHODS
RESULTS
DISCUSSION AND CONCLUSION
REFERENCES
Preliminary Experiments
σt is the tensile fracture strength of the tablet, P is the fracture force (N), D is the tablet diameter, t is the overall thickness
Mannitol grade Parteck (Merck)
Mannitol grade Perlitol (Roquette)
Isomaltulose (Beneo-Palatinit)
Parteck M100
Perlitol 100SD
Galen IQ720
Parteck M200
Perlitol 200SD
Galen IQ721
Parteck M300
Perlitol 300DC
Perlitol 400DC
Perlitol 500DC
Main Experiments We have shown previously that the Gamlen Tablet Press GTP-1 can rapidly evaluate formulations for tablet development using milligram quantities of material. Uniquely for a tablet press it gives precise information on the compression force, ejection force and fracture force of an individual tablet, providing valuable information for the required target product profile, required for Quality by Design (QbD). We present in this work an evaluation of a number of different direct compression excipients in the development of a paracetamol tablet. We evaluated a number of different direct compression excipients to prepare a formulation containing 10% paracetamol. The formulations were blended for 30 minutes and lubricated with 0.5% magnesium stearate for a further 5 minutes in a blender. Each formulation was then compacted using the Gamlen Tablet Press GTP-1 to produce round flat face tablets. Tablets weresubjected to tensile strength, friability and disintegration testing, whilst the formulation was tested for flowability and LOD. The initial experiments showed clear differences between formulations in compressibility, friability, disintegration and powder flowability. Among the mannitol grades the compressibility of the SD types was better than the DC types. Very high ejection forces were recorded despite use of a lubricant. Individual ejection profiles analysed by the GTP-1 revealed the important relationship of material properties with ejection of the tablet from the die- a key determinant of suitability for rotary press manufacture. The main experiments characterised the compressibility and tablet behaviour of the most compressible excipients, with the low API% formulas performing best. Evaluation of a wide range of formulations using using the GTP-1 provided valuable information on compression force, ejection force and disintegration times of individual tablets using very small amounts of material. This enables an evaluation of the widest possible tablet quality and tablet/ material processing parameters to aid formulation development.
ABSTRACT
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck M100
14.5 16 0.27
Parteck M200
12.9 20 0.17
Parteck M300
7.4 14 0.19
Perlitol 100SD
13.5 20 0.16
Perlitol 200SD
11.63 18 0.11
Perlitol 300DC
8.3 10 0.14
Perlitol 400DC
6.7 8 0.11
Perlitol 500DC
8.1 5 0.14
Galen IQ720
11.25 16 4.07
Galen IQ721
13.4 12 1.5
Formulation Compressibility Index (%)
Minimum orifice size
LOD%
Parteck 0.1% 16.25 18 0.81
Parteck 1% 16.25 16 1.13
Parteck 10% 17.5 22 1.10
Perlitol 0.1% 11.25 12 0.96
Perlitol 1% 8.75 16 0.98
Perlitol 10% 16.25 18 1.32
Galen 0.1% 13.75 7 2.70
Galen 1% 16.25 8 2.65
Galen 10% 16.25 20 2.21
REFERENCES
Fell JT and Newton JM. Determination of tablet strength by the diametral compression test. J Pharm Sci 59; 688-691, 1970 Pitt & Heasley. Powder Technology 2012.
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