review on week 6 lecture
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Review on Week 6 Lecture. Particle Based Drug Delivery System. Delivery Problems. There are several problem in delivering drugs to humans High dose or high frequency of dose Patient discomfort or rejection of drug - PowerPoint PPT PresentationTRANSCRIPT
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Review on Week 6 Lecture
Particle Based Drug Delivery System
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Delivery ProblemsThere are several problem in delivering drugs to
humans High dose or high frequency of dose Patient discomfort or rejection of drug Objective: to kill cancer/undesired cells without
killing other non-cancer/useful cells Example: To avoid over dosage
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Plasma Drug Concentration Profile This profile is important because it
shows the maximum limit, controlled release and minimum limit which is base on:
Minimum effective level: prevention of material wastage
Maximum effective level: prevention of increasing risk
Techniques introduced to achieve sustainable release eg by compressed tablets
HOWEVER….problems still exist Amount of drug released
depends on patients conditions Environmental effects Repeated dosage required
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Controlled Polymeric Delivery System
Advantages Less expensive Less wastage of
material used Reduce side effects
which are harmful
Disadvantages Sometimes can be
expensive Sometimes can
produce harmful by-products if its biodegradable
Lack of biocompatibility
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Diffusion(Commonly used)
Reservoirs Surrounded by polymer films Diffusion of drug via rate
limiting step E.g membranes or capsules Polymer used like silicone
rubber Disadvantages are its
expensive and rapid release Able to achieve “zero” order
kinetics
Types of Controlled Drug Release Polymeric System
At Time= 0
At Time= t
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Types of Controlled Drug Release Polymeric System
Matrices Uniformly distributed Diffusion of drug via rate
limiting step Not generally “zero” order
At Time= 0
At Time= t
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Chemically Controlled System
Bioerodible Distributed uniformly like
matrices Polymer degrades with time
and release drug at the same time
At Time= 0
At Time= t
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Chemically Controlled SystemPendant Chain
Chemically bound to polymer backbone chain
Released by hydrolytic/enzymatic cleavage
Degrades by hydrolytic Heterogeneous degradation:
Occurs at carrier surface Constant degradation rate Chemically integrity retained in smaller
portion Homogeneous degradation
Random cleavage throughout polymer bul Molecular Weight decreases steadily At critical MW, solubilisation and mass
loss happens
At Time= 0
At Time= t
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Swelling Controlled System
Using glass or rubbery state polymer
Drug dissolved or dispersed in polymer
Dissolution medium penetrates matrix and swells the backbone
When swollen polymer in rubbery state, drug diffusion occurs
At Time= 0
At Time= t
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Magnetically Controlled System
Drug and small magnetic beads dispersed in polymer matrix
Upon medium exposure, release like matrix system
Upon exposure to oscillating external magnetic field, more release rate
At Time= 0
At Time= tOscillating magnetic field
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Types of polymers used in drug release
Hydrophilic Polymers Tendency to interact or dissolved by water Reservoir and monolithic devices prepared from swollen cross-linked hydrophilic
polymers Eg PVA (Poly Vinyl Alcohol)
Hydrophobic Polymers Repels water Polymer available as uncross-linked matrices or membranes Eg EVAC ( Ethylene Vinyl Acetate)
Biodegradable Polymers Degrades over time Eg PLA (PolyLactic Acid)
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Fabrication of drug delivery devices
Tutorial 7Present to you by group 1
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Overview
Electro-spinning Electrodynamic Atomization-EHDA Supercritical Antisolvent with enhance mass transfer- (SAS-ME)
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Electro-spinning
Electro spinning uses an electrical charge (high voltage) to draw very fine (typically on the micro or nano scale) fibres from a liquid.
• Fabricating poly(lactic-co-glycolic acid)-PLGA microfiber.• Size range from 3nm to more than 5 microns.
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Diagram of a electro spinning
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Parameter that affect the formation and structure of produced nanofibers
1. SOLUTION Viscosity Solution concentration Molecular weight of the polymer Solvent properties Surface tension Conductivity
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Parameter that affect the formation and structure of produced nanofibers
2. PROCESS– Voltage applied– Distance of the electrode from the collector– Flow rate– Capillary geometry
3. ENVIRONMENT– Temperature– Relative humidity
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Effects of controlling parameter on fiber diameter
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Electrodynamic Atomization(EHDA)
Similar to electro spinning, EDHA applies electrical stress (high voltage) on the fluid that emerges from the tip of the nozzle, which forms a Taylor cone that decreases the diameter of the jet.• Fabricating paclitaxel-loaded PCL/PLGA micro particles• Particle sizes ranges in micron scale
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Diagram of a EHDA set-up
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Parameter that affect the formation and structure of produced Micro Particle
1. SOLUTION– Viscosity– Solution concentration– Molecular weight of the polymer– Solvent properties– Surface tension– Conductivity
2. PROCESS– Voltage applied– Flow rate– Capillary geometry
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Supercritical Antisolvent with enhance mass transfer- (SAS-ME)
SAS supercritical antisolvent SAS supercritical antisolvent with enhanced mass transfer
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Supercritical Antisolvent with enhance mass transfer- (SAS-ME)
SAS• Uses CO2 as an anti-solvantThe advantages of supercritical fluid processing include mild operating temperatures, production of solvent free particles and easy micro encapsulation of particles.• The operating temperature, pressure and concentration of the
injecting solution have so far been investigated as size control parameters, but none of these parameters have been found to produce a significant decrease in the particle size over a wide range.
• Therefore it is unable to produce fine particles in the sub-micron range (<300 nm)
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Supercritical Antisolvent with enhance mass transfer- (SAS-ME)
SAS-ME• Use supercritical carbon dioxide as the anti solvent• Utilizes a surface, vibrating at an ultrasonic frequency to atomize the
solution jet into micro-droplets. Moreover, the ultrasound field greatly enhances turbulence and mixing within the supercritical phase resulting in high mass transfer between the solution and the antisolvent.
• The combined effect of fast rate of mixing between the antisolvent and the solution, and reduction of solution droplet size due to atomization, provides particles approximately ten-fold smaller than those obtained from the conventional SAS process.
• Able to produce particles in the nanometer range having a very narrow size distribution.
![Page 25: Review on Week 6 Lecture](https://reader036.vdocuments.net/reader036/viewer/2022062310/568163a9550346895dd4bb6e/html5/thumbnails/25.jpg)
Supercritical Antisolvent with enhance mass transfer- (SAS-ME)
Results of the precipitation experiments conducted using the SASEM technique at 96.5 bar, 37 degreeC and at different values of ultrasound power supply, for various pharmaceutical compounds, have been shown below.
Source: http://www.isasf.net/fileadmin/files/Docs/Versailles/Papers/Md3.pdf
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Conclusion
Advantages of nano particle drug delivery system:1. improved bioavailability by enhancing aqueous solubility2. increasing resistance time in the body(sustained release of drug)3. targeting drug to specific location in the body (its site of action).This results in concomitant reduction in quantity of the drug required and dosage toxicity, enabling the safe delivery of toxic therapeutic drugs and protection of non target tissues and cells from severe side effects.
![Page 27: Review on Week 6 Lecture](https://reader036.vdocuments.net/reader036/viewer/2022062310/568163a9550346895dd4bb6e/html5/thumbnails/27.jpg)
Fabrication of drug delivery devices
Tutorial 7Present to you by group 1
![Page 28: Review on Week 6 Lecture](https://reader036.vdocuments.net/reader036/viewer/2022062310/568163a9550346895dd4bb6e/html5/thumbnails/28.jpg)
Overview
• Electro-spinning • Electrodynamic Atomization-EHDA• Supercritical Antisolvent with enhance mass transfer- (SAS-ME)
![Page 29: Review on Week 6 Lecture](https://reader036.vdocuments.net/reader036/viewer/2022062310/568163a9550346895dd4bb6e/html5/thumbnails/29.jpg)
Electro-spinning
Electro spinning uses an electrical charge (high voltage) to draw very fine (typically on the micro or nano scale) fibres from a liquid.
• Fabricating poly(lactic-co-glycolic acid)-PLGA microfiber.• Size range from 3nm to more than 5 microns.
![Page 30: Review on Week 6 Lecture](https://reader036.vdocuments.net/reader036/viewer/2022062310/568163a9550346895dd4bb6e/html5/thumbnails/30.jpg)
Diagram of a electro spinning
![Page 31: Review on Week 6 Lecture](https://reader036.vdocuments.net/reader036/viewer/2022062310/568163a9550346895dd4bb6e/html5/thumbnails/31.jpg)
Parameter that affect the formation and structure of produced nanofibers
1. SOLUTION– Viscosity– Solution concentration– Molecular weight of the polymer– Solvent properties– Surface tension– Conductivity
![Page 32: Review on Week 6 Lecture](https://reader036.vdocuments.net/reader036/viewer/2022062310/568163a9550346895dd4bb6e/html5/thumbnails/32.jpg)
Parameter that affect the formation and structure of produced nanofibers
2. PROCESS– Voltage applied– Distance of the electrode from the collector– Flow rate– Capillary geometry
3. ENVIRONMENT– Temperature– Relative humidity
![Page 33: Review on Week 6 Lecture](https://reader036.vdocuments.net/reader036/viewer/2022062310/568163a9550346895dd4bb6e/html5/thumbnails/33.jpg)
Effects of controlling parameter on fiber diameter
![Page 34: Review on Week 6 Lecture](https://reader036.vdocuments.net/reader036/viewer/2022062310/568163a9550346895dd4bb6e/html5/thumbnails/34.jpg)
Electrodynamic Atomization(EHDA)
Similar to electro spinning, EDHA applies electrical stress (high voltage) on the fluid that emerges from the tip of the nozzle, which forms a Taylor cone that decreases the diameter of the jet.• Fabricating paclitaxel-loaded PCL/PLGA micro particles• Particle sizes ranges in micron scale
![Page 35: Review on Week 6 Lecture](https://reader036.vdocuments.net/reader036/viewer/2022062310/568163a9550346895dd4bb6e/html5/thumbnails/35.jpg)
Diagram of a EHDA set-up
![Page 36: Review on Week 6 Lecture](https://reader036.vdocuments.net/reader036/viewer/2022062310/568163a9550346895dd4bb6e/html5/thumbnails/36.jpg)
Parameter that affect the formation and structure of produced Micro Particle
1. SOLUTION– Viscosity– Solution concentration– Molecular weight of the polymer– Solvent properties– Surface tension– Conductivity
2. PROCESS– Voltage applied– Flow rate– Capillary geometry
![Page 37: Review on Week 6 Lecture](https://reader036.vdocuments.net/reader036/viewer/2022062310/568163a9550346895dd4bb6e/html5/thumbnails/37.jpg)
Supercritical Antisolvent with enhance mass transfer- (SAS-ME)
SAS supercritical antisolvent SAS supercritical antisolvent with enhanced mass transfer
![Page 38: Review on Week 6 Lecture](https://reader036.vdocuments.net/reader036/viewer/2022062310/568163a9550346895dd4bb6e/html5/thumbnails/38.jpg)
Supercritical Antisolvent with enhance mass transfer- (SAS-ME)
SAS• Uses CO2 as an anti-solvantThe advantages of supercritical fluid processing include mild operating temperatures, production of solvent free particles and easy micro encapsulation of particles.• The operating temperature, pressure and concentration of the injecting solution have so far been investigated as
size control parameters, but none of these parameters have been found to produce a significant decrease in the particle size over a wide range.
• Therefore it is unable to produce fine particles in the sub-micron range (<300 nm)
![Page 39: Review on Week 6 Lecture](https://reader036.vdocuments.net/reader036/viewer/2022062310/568163a9550346895dd4bb6e/html5/thumbnails/39.jpg)
Supercritical Antisolvent with enhance mass transfer- (SAS-ME)
SAS-ME• Use supercritical carbon dioxide as the anti solvent• Utilizes a surface, vibrating at an ultrasonic frequency to atomize the solution jet into micro-droplets. Moreover,
the ultrasound field greatly enhances turbulence and mixing within the supercritical phase resulting in high mass transfer between the solution and the antisolvent.
• The combined effect of fast rate of mixing between the antisolvent and the solution, and reduction of solution droplet size due to atomization, provides particles approximately ten-fold smaller than those obtained from the conventional SAS process.
• Able to produce particles in the nanometer range having a very narrow size distribution.
![Page 40: Review on Week 6 Lecture](https://reader036.vdocuments.net/reader036/viewer/2022062310/568163a9550346895dd4bb6e/html5/thumbnails/40.jpg)
Supercritical Antisolvent with enhance mass transfer- (SAS-ME)
Results of the precipitation experiments conducted using the SASEM technique at 96.5 bar, 37 degreeC and at different values of ultrasound power supply, for various pharmaceutical compounds, have been shown below.
Source: http://www.isasf.net/fileadmin/files/Docs/Versailles/Papers/Md3.pdf
![Page 41: Review on Week 6 Lecture](https://reader036.vdocuments.net/reader036/viewer/2022062310/568163a9550346895dd4bb6e/html5/thumbnails/41.jpg)
Conclusion
Advantages of nano particle drug delivery system:1. improved bioavailability by enhancing aqueous solubility2. increasing resistance time in the body(sustained release of drug)3. targeting drug to specific location in the body (its site of action).This results in concomitant reduction in quantity of the drug required and dosage toxicity, enabling the safe delivery of toxic therapeutic drugs and protection of non target tissues and cells from severe side effects.