studies on tableting properties of mixture containing...

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Impact factor: 3.958/ICV: 4.10 ISSN: 0976-7908 338 Arpit et al. / Pharma Science Monitor 8(2), Apr-Jun 2017, 338-353 Pharma Science Monitor 8(2), Apr-Jun 2017 STUDIES ON TABLETING PROPERTIES OF MIXTURE CONTAINING SARPAGANDHA ROOT POWDER UNDER THE IMAPCT OF VARIOUS EXCIPIENTS A. K. Patel*, T. M. Patel Department of Pharmaceutics and Pharmaceutical technology, L.M.College of Pharmacy, Navrangpura, Ahmedabad-380009, Gujarat, India ABSTRACT The objectives of this study were to check the compression and compaction behaviour of Sarpagandha root powder with different excipients i.e. Avicel PH 102, Avicel PH 200, Directly compressible lactose 21, Starch 1500, Dicalcium phosphate dihydrate, Dicalcium phosphate, tricalcium phosphate and lactose monohydrate.In this work, direct compression and dry granulation methods were used for tablet preparation. Comparison of direct compression and dry granulation were also carried out. Tableting properties such as flow property, compressibility and compactibility were evaluated. Compressibility and compactibility attributes of Sarpagandha root powder with different excipient were determined with Heckel Plot, Walker analysis, Kawakita’s equation, and Kuno’s equation. In direct compression process, Avicel PH 200 mixture was found to be superior as compared to other directly compressible excipient. In case of dry granulation process, Tricalcium phosphate (TCP) has was found to be higher in comparison with other excipients studied. However, direct compression with Avicel PH 200 mixture exhibited improved flow properties and compressibility at low yield pressure as linked to granules prepared by dry granulation with TCP. Walker co-efficient promote the results obtained from Heckel analysis. KEYWORDS: Compressibility, Compactibility, Sarpagandha root powder, Heckel plot, Walker analysis. INTRODUCTION The objective of the present work was to study the tableting properties of Sarpagandha root powder in presence of various tableting excipients. The root powder is obtained from Rauwolfia serpentine Bentham ex Kurz roots (Family: Apocynaceae) which is widely used as antihypertensive. [1-2] Due to poor flowability and compaction behaviour, sarpagandha powder frequently request a granulation prior to tableting. To increase the therapeutic performance and stability of sarpagandha root powder, methods like direct compression (DC) and dry granulation (DG) can be used. Moreover, direct compression and dry granulation is correlated with lower cost and less PHARMA SCIENCE MONITOR AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES Journal home page: http://www.pharmasm.com

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Impact factor: 3.958/ICV: 4.10 ISSN: 0976-7908 338

Arpit et al. / Pharma Science Monitor 8(2), Apr-Jun 2017, 338-353

Pharma Science Monitor 8(2), Apr-Jun 2017

STUDIES ON TABLETING PROPERTIES OF MIXTURE CONTAINING

SARPAGANDHA ROOT POWDER UNDER THE IMAPCT OF VARIOUS

EXCIPIENTS

A. K. Patel*, T. M. Patel

Department of Pharmaceutics and Pharmaceutical technology, L.M.College of Pharmacy, Navrangpura,

Ahmedabad-380009, Gujarat, India

ABSTRACT

The objectives of this study were to check the compression and compaction behaviour of

Sarpagandha root powder with different excipients i.e. Avicel PH 102, Avicel PH 200, Directly

compressible lactose 21, Starch 1500, Dicalcium phosphate dihydrate, Dicalcium phosphate,

tricalcium phosphate and lactose monohydrate.In this work, direct compression and dry

granulation methods were used for tablet preparation. Comparison of direct compression and dry

granulation were also carried out. Tableting properties such as flow property, compressibility and

compactibility were evaluated. Compressibility and compactibility attributes of Sarpagandha root

powder with different excipient were determined with Heckel Plot, Walker analysis, Kawakita’s

equation, and Kuno’s equation. In direct compression process, Avicel PH 200 mixture was found

to be superior as compared to other directly compressible excipient. In case of dry granulation

process, Tricalcium phosphate (TCP) has was found to be higher in comparison with other

excipients studied. However, direct compression with Avicel PH 200 mixture exhibited

improved flow properties and compressibility at low yield pressure as linked to granules

prepared by dry granulation with TCP. Walker co-efficient promote the results obtained from

Heckel analysis.

KEYWORDS: Compressibility, Compactibility, Sarpagandha root powder, Heckel plot, Walker

analysis.

INTRODUCTION

The objective of the present work was to study the tableting properties of Sarpagandha root

powder in presence of various tableting excipients. The root powder is obtained from Rauwolfia

serpentine Bentham ex Kurz roots (Family: Apocynaceae) which is widely used as

antihypertensive. [1-2]

Due to poor flowability and compaction behaviour, sarpagandha powder frequently request a

granulation prior to tableting. To increase the therapeutic performance and stability of

sarpagandha root powder, methods like direct compression (DC) and dry granulation (DG) can

be used. Moreover, direct compression and dry granulation is correlated with lower cost and less

PHARMA SCIENCE MONITOR

AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES

Journal home page: http://www.pharmasm.com

Impact factor: 3.958/ICV: 4.10 ISSN: 0976-7908 339

Arpit et al. / Pharma Science Monitor 8(2), Apr-Jun 2017, 338-353

time consuming manufacturing process. Conventional wet granulation incorporatesmixing of the

powders, adding of agglomerating solution, kneeding or massing of moist powders.[3]By the use

of directly compressible excipient one can compress tablet of sufficient mechanical strength by

using different excipients.

The description and proper explanation of the properties of pharmaceutical materials is critical to

effectively and rationally develop pharmaceutical dosage forms. The practical performance of

tablet excipients can be assessed with the excipients as powders, as a dosage form of pure

excipients and as a formulation of a given drug holding the excipients. The excipients are

involved in a formulation as they own properties that in conjunction with a process let the

production of a dosage form with the mandatory specifications.

The part of excipients in drug product development includes targeting the drug profile andcontrol

the final characteristics of the ending product. The efficientpresentation of tablet excipients can

be measured with the excipients as powders, dosage form of pure excipients and as a formulation

of a given drug containing the excipients.[4]

The aim of this work is to check compressibility and compactibility of mixtures of Sarpagandha,

directly compressible diluents, glidants and lubricants will be prepared in order to finalize the

optimal ratio of active material and excipients which furnish a sufficient mechanical strength of

tablets. Directly compressible diluents considered in this study include Microcrystalline cellulose

(Avicel PH 102 and Avicel PH 200), directly compressible lactose (DCL 21), Dicalcium

phosphate dehydrate, Tricalcium phosphate, Dicalcium phosphate and Pregelatinized starch

(Starch 1500). Excipients used in this study for dry granulation include Microcrystalline

cellulose (Indian pharmacopoeia grade), Dicalcium phosphate dihydrate (powder form), Lactose

monohydrate, Tricalcium phosphate and Dicalcium phosphate. DC excipients shows some

benefit such as good flow properties and high mechanical strength of tablets.

MATERIALS AND METHODS

Materials

Sarpagandha root powder was purchased online from R.R. Herbals, Tamilnadu with batch No:

Q21. Microcrystalline cellulose (Avicel PH 102; Avicel PH 200 and Indian Pharmacopoeia

grade); directly compressible lactose (DCL 21); dicalcium phosphate dehydrate were obtained as

gift sample from Intas Pharmaceuticals Limited, Ahmedabad. Dicalcium phosphate; tricalcium

phosphate; lactose monohydrate; crosscarmellose sodium, talc, magnesium stearate were

purchased fromFinar Chemicals India Pvt. Ltd.; Ahmedabad. All the excipients were stored in

air tight containers at 25 ± 2 °C and 40 ± 5 % RH conditions.

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Preparation of tableting mixtures by direct compression

Accurately weighed quantity of Sarpagandha root powder, directly compressible diluent,

crosscarmellose sodium, talc, magnesium stearate are passed separately through sieve of mesh

size 40. All ingredients except magnesium stearate are mixed for 5 min in a cone shaped blender.

The composition was again mixed with magnesium stearate for 2 minutes. The powder mixture

was directly compressed in a rotary tablet compression machine. Capsule shaped punch sets were

used with the dimensions of 21.10 mm X 10.10 mm. Average weight of tablets prepared by

direct compression was 914 mg.

Preparation of tableting mixtures by Dry Granulation

Accurately weighed quantity of sarpagandha root powder, Non DC diluent, crosscarmellose

sodium, talc, magnesium stearate are passed separately through sieve of mesh size 40. All

ingredients are mixed in for 5 minutes in cone shaped blender. Slugs are produced by

compressing the material in rotary tablet compression machine by using 20/32” flat round shaped

punches. Slugs are milled through # 20 sieve to prepare granules. The granules are compressed

in rotary tablet punching machine to prepare tablets. Capsule shaped punch sets were used with

the dimensions of 21.10 mm X 10.10 mm. Average weight of tablets prepared by direct

compression was 702 mg.

Characterization of tableting mixtures and tablets

Flow properties of tableting mixture

Flow properties of the tableting mixture were determined by measuring the angle of repose and

Carr’s index as per USP29-NF24 (<1174> Powder flow).[5]

Tablet crushing strength

Tablet breaking force was determined by diametric compression on a Dr. Schleuniger

Pharmatron Tablet Tester 8M according to USP29-NF24 (<1217> Tablet breaking force).[6]

Tablet friability

Tablet friability (%) was determined according to USP29-NF24 (<1216> Tablet friability) by

using a friability tester Electrolab Friabilator USP (XXIII).[7]

Tablet disintegration

Disintegration time was measured by using disintegration machine THERMONIK, Campbell

Electronics TD-2 as per USP29-NF24 (<701> Disintegration). [8]

Compressibility

Heckal plot

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The most commonly practical method in pharmaceutical technology for evaluating

compressibility is the Heckel model. The Heckel equation delivers a method of compression

pressure and displacement signals to linear relationship for materials undertaking compaction.

The equation undertakes that at applied pressure the densification of powder bed follows first

order, with inter particulate pores as the reactant and the densification of the powder bed as the

product.[9] Tableting mixtures containing sarpagandha and diluents were compressed using 12

mm diameter of flat faced punch at various applied pressures (0.5, 1, 1.5, 2, 2.5 and 3 tons) using

KBr press (Wika quality systems, Germany). The die and punch were lubricated using 1% w/v

dispersion of Magnesium stearate in acetone. Heckel equation is described by the formula:

−ln = (1

1−D) = KP + A (1)

Where, 'D' is the solid fraction (the ratio of tablet density to true density of powder) at applied

pressure 'P' in tons. (1-D) denotes the % porosity (Є) of the powder material. 'K' is the material-

dependent constant (the slope of the straight line portion of the Heckel plot). The reciprocal of

'K' is the mean yield pressure (Py) Intercept 'A' gives the densification of the powder bed as a

result of initial particle rearrangement.

'D' value was calculated by determining the diameter and thickness of the compacts after each

applied pressure in tons. Compression behavior of the respective powders was expressed as

parameters of Heckel equation. Heckel analysis was carried out by intrigue the graph of ln (1

1−𝐷)

Vs P. A high Heckel coefficient displays a materials propensity towards fragmentation, while a

low value means that the material is plastically deformable [16-17]. Heckal reported that the

linear portion of the plot represents the densification process by particle deformation after

intraparticular bonding and that soft, ductile powders have lower yield pressure. Agglomerates

that have the lowest value undergo plastic deformation. The yield pressure value reflects the

compression characteristics of the material: the lesser the value of (Py), the greater the tendency

towards plastic deformation.

Walker analysis

Walker equation is used for compressibility study. It involves plotting the specific volume of the

powder compact against logarithm of the axial pressure applied.[10]The equation is described by:

V’ = w’ logP + V’sp (2)

Where, V’ is specific volume of a tablet and w’ is the walker coefficient stating the volume

reduction corresponding to change in pressure P obtained by linear regression analysis and V’sp

is the specific volume at pressure 1 (ton) of KBr press.[11]

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Compactibility

Kawakita’s equation

The packability of agglomerates of the tableting mixture containing sarpagandha and diluents

was established by comparing the constants a, b and k in Kawakita’s and Kuno’s equations,

respectively. For the analysis purpose, 20 gm of tableting mixture was tapped in the 100ml

measuring cylinder on a tap density tester (Electrolab ETD-1020, India). Initial bulk volume (v0)

was noted. Thereafter tapped volume was noted after predetermined taps

(5,10,15,20,25,50,75,100,200,300,400 and 500). The tapped volume at 500th tap is referred to as

equilibrium volume. The data were analyzed using following equation,

n

c=

1

ab+

n

a (3)

Where,

a =(v0−vinf)

v0 ; c =

(v0−vn)

v0; n = tap number; V0, Vn and Vinf are the powder bed volumes at initial,

after nth tapping (5, 10, 15, 20, 25, 50, 75, 100, 200, 300 and 400 ) and at equilibrium state (500th

tap) respectively. The constant ‘a’ represents the proportion of consolidation as closest packing is

attained. The reciprocal of b and k represents the packing velocity.

Kuno’s equation

For the analysis purpose, 20 gm of tableting mixture containing sarpagandha and diluents was

tapped in the 100ml measuring cylinder on a tap density tester (Electrolab ETD-1020, India).

Initial bulk volume (v0) was noted. Thereafter tapped volume was noted after predetermined taps

(5, 10, 15, 20, 25, 50, 75, 100, 200, 300, 400 and 500). The tapped volume at 500th tap is referred

to as equilibrium volume. The data were analyzed using following equation:

ρf

− ρn

= (ρf

− ρ0

)e−kn (4)

Where, ρ0, ρn and ρf are the apparent densities at initial state, after nth tapping, and at equilibrium

state respectively; and n is number of taps.

Tensile strength

The tensile strength (σ) calculated using following equation,

σ =2𝐻

П𝑑ℎ; (5)

Where, H is the tablet crushing force, d is the tablet diameter and h is the tablet thickness.[13]

Elastic recovery

The compacts used in the Heckel plot analysis were subjected to relaxation period of 24 hours to

critic the elastic behavior of the powder bed under examination. The thickness of compacts was

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recorded instantly after ejection (Hc) from the KBr press and after 24 hours relaxation period

(He).[13]

%ER= [ (He−Hc)

Hc] × 100 (6)

Results and discussion

Characterization of mixtures

Flow properties of tableting mixture

The flow properties results are shown in table 1. The flow properties are evaluated in terms of

Carr’s index and angle of repose. Good flow properties was observed with the tableting mixture

Avicel PH 102, Avicel PH 200, DCL 21, Starch-1500, DCP and TCP in case of direct

compression. In case of dry granulation, tableting mixture showed good flow property after

slugging and milling process.

Table1: Flow properties of Different Directly compressible excipients with Sarpagandha

root powder for direct compression method

Batch

No

Excipient in

tableting

Mixture*

AOR

(º)

Bulk

Density

(gm/cm3)

Tapped

density

(gm/cm3)

Carr’s

Index

(%)

Flow

properties

SAT3 Avicel PH 102 33.60 0.8 0.71 0.3 0.83 0.3 14.46 Good

SAT6 Avicel PH 200 33.40 1.2 0.65 0.5 0.76 0.4 14.48 Good

SAT9 DCL 21 32.16 0.9 0.84 0.3 0.95 0.2 11.57 Good

SAT12 DCPD 38.320.8 0.89 0.3 1.11 0.3 19.81 Poor

SAT15 Starch-1500 31.76 0.9 0.89 0.2 1.00 0.2 11.00 Good

SAT18 DCP 34.50 0.4 0.98 0.4 1.17 0.2 16.24 Good

SAT21 TCP 34.10 0.7 0.90 0.4 1.05 0.2 14.29 Good

*Each batch contains excipients (525mg); Sarpagandha root powder (325mg); Crosscarmellose

sodium (5%), Talc (2%), and magnesium stearate (1%). DCL 21= directly compressible lactose

21; DCPD=Dicalcium phosphate dihydrate; DCP=Dicalcium phosphate; TCP=Tricalcium

Phosphate

Hardness, Friability and Disintegration of tablet

The hardness, friability and disintegration time of tablets prepared from selected batches of

mixture as per good flow properties are shown in table 2. It is surprisingly to know that each

excipient shows different hardness, friability and disintegration time with direct compression and

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dry granulation method. Tablets produced should possess more than 40N hardness and friability

should not be more than 1% as USP. Excipients which shows good flow properties and good

hardness with the drug are further selected for the compressibility and compactibility studies.

Table 2: Hardness, Friability and Disintegration time of tablets produced from selected

batches of direct compression method

Batch No Excipient Hardness

(Newton)

N=5

Friability

(%)

Disintegration

time (min)

N=5

SAT3 Avicel PH 102 119 7 0.49 1 1

SAT6 Avicel PH 200 108 5 0.64 1 1

SAT9 DCL 21 154 5 0.31 1 1

SAT15 Starch-1500 52 6 Tablet breaks -

SAT18 DCP 57 4 Tablet breaks -

SAT21 TCP 98 8 0.71 1 1

Table 3: Flow properties of tableting mixture prepared by dry granulation method

Batch No Excipient AOR

(º)

Bulk

Density

(gm/cm3)

Tapped

density

(gm/cm3)

Carr’s

Index

(%)

Flow

properties

SATD1 MCC IP 33.74 1.3 0.860.4 0.950.3 11.62 Good

SATD2 LM 32.54 0.9 0.80 0.3 0.95 0.2 18.75 Good

SATD3 DCPD 31.13 1.5 0.71 0.3 0.95 0.2 25.00 Good

SATD4 TCP 34.21 1.1 0.74 0.3 0.86 0.3 16.21 Good

* Each batch contains excipients (325mg); sarpagandharoot powder (325mg); crosscarmellose

sodium (5%); talc (2%), and magnesium stearate (1%).

Table 4: Hardness, Friability and Disintegration time of tablets prepared by dry

granulation method

Batch No Excipient Hardness

(Newton)

N=5

Friability

(%)

Disintegration time

(min)

N=5

SATD1 MCC IP 60 8 0.28 1 1

SATD2 LM 71 5 0.37 1 1

SATD3 DCPD 117 10 0.19 1 1

SATD4 TCP 82 9 0.44 1 1

*Batches were selected based on Hardness and Friability acceptability criteria.

Compressibility

Compressibility is the ability to deform under pressure. The compressibility profile of DCL

21/Avicel PH 200 for direct compression and TCP for dry granulation showed the highest

porosity compared to other materials as well as the smallest changes in porosity over the

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compression pressure range, implying that it has the better compressibility. On the other side,

DCL 21 for direct compression and DCPD and LM for dry granulation showed more comparable

porosity profiles.

Heckal plot

Table 5: compressibility of tableting mixture studied using the heckel plot, where k

represents the heckel coefficient and Py, yield pressure; DC=Direct compression, DG= Dry

granulation

Figure 1: Comparison of Heckel plot (Direct compression)

0

1

2

3

4

5

6

0 0.5 1 1.5 2 2.5 3 3.5

ln(1

/)

Pressure in ton

Comparision of Heckel plot(sarpagandga direct compression)

Avicel PH 102 Avicel PH 200 DCL 21 TCP

Batch No Material R2 k

(Heckel co-

efficient)

Yield Pressure (Py)

(ton)

SAT 3 (DC) Avicel PH 102 0.841 1.0096 0.9904

SAT 6 (DC) Avicel PH 200 0.941 1.4845 0.6736

SAT 9 (DC) DCL 21 0.863 1.0015 0.9985

SAT 21 (DC) TCP 0.829 0.9144 1.0936

SATD 1 (DG) MCC IP 0.942 1.1876 0.8420

SATD 2 (DG) LM 0.910 1.0422 0.9542

SATD 3 (DG) DCPD 0.883 0.8769 1.1403

SATD 4 (DG) TCP 0.944 1.4082 0.7101

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Figure 2: Comparison of Heckel plot (Dry granulation)

Table 6: Comparison of Results of the Heckel co-efficient (k) and Walker co-efficient (W’)

Batch No Excipient k W’ * 100 (%)

SAT 3 (DC) Avicel PH 102 1.0096 126.6

SAT 6 (DC) Avicel PH 200 1.4845 149.6

SAT 9 (DC) DCL 21 1.0015 145.8

SAT 21 (DC) TCP 0.9144 97.2

SATD 1 (DG) MCC IP 1.1876 83.41

SATD 2 (DG) LM 1.0479 84.7

SATD 3 (DG) DCPD 0.8769 68.9

SATD 4 (DG) TCP 1.4082 94.9

Considering the heckel co-efficient, material compressibility decreases in the following

order,Avicel PH 200>Avicel PH 102>DCL 21>TCP in case of direct compression. In case of dry

granulation, the compressibility order was found: DCPD>LM>MCC IP>TCP. A similar trend

was found in the Walker Co-efficient. Higher values of w’ and k are indicators of a better

compressibility (plasticity) of the powder.

The direct mixtures compressibility, is comparable with that of the dry granulation mixtures,

most certainly lies as the choice of input raw materials that are themselves originally suitable for

direct tableting. Mixture of direct compressible excipient shows even better compressibility than

that of single directly compressible excipient. The lower compressibility of dry granulated

mixture maybe partly attributed to double particle processing. In the slugging process and

0

1

2

3

4

5

6

0 0.5 1 1.5 2 2.5 3 3.5

ln (

1/

)

Pressure in ton

Comparision of Heckel plot(sarpagandha dry granulation)

MCC IP DCPD TCP LM

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compacting, particles are milled and compressed using the dry granulation step and

recompressed during tableting. The reduction in the dry granulated mixtures compressibility may

be attributed to work hardening.[11]

Walker analysis

The walker plots is described by inverse of pressure versus specific volume. The walker model

once again proved that the most compressible mixture is the tableting mixture containing

sarpagandha root powder with Avicel PH 200 with w’ of 149.6 for direct compression. For dry

granulation, most compressible mixture was found to be the mixture containing TCP with the

value of w’ of 94.98. The results of walker analysis was found according to the pattern of

Heckel’s plot. It is important to emphasize that the walker model’s has slightly better

discriminative power over the heckel’s model to differentiate tableting mixture compressibility.

Table 7: Compressibility of tableting mixture studied according to the Walker model

Batch No Excipient w’ * 100 (%) R2

SAT 3 (DC) Avicel PH 102 126.6 0.9846

SAT 6 (DC) Avicel PH 200 149.6 0.8439

SAT 9 (DC) DCL 21 145.8 0.9826

SAT 21 (DC) TCP 97.2 0.9809

SATD 1 (DG) MCC IP 83.41 0.9542

SATD 2 (DG) LM 84.78 0.974

SATD 3 (DG) DCPD 68.95 0.9361

SATD 4 (DG) TCP 94.98 0.9994

Figure 3: Comparison of Walker analysis (Direct compression)

0

100

200

300

400

500

600

700

800

0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4 0.45 0.5

Spec

ific

vo

lum

e

log P

Comparision of walker analysis(Sarpagandha direct compression)

Avicel PH 102 Avicel PH 200 DCL 21 TCP

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Figure 4: Comparison of Walker analysis (Dry granulation)

Compactibility

Compactibility is the materials ability to produce tablets of sufficient mechanical strength under

the pressure applied. The mechanical strength of the compact associated with the number of

contacts point generated. The compactibility of a specific substance can be represented by a plot

of tensile strength versus compression pressure or by the compactibility co-efficient (Cp) which

is determined as the slope of the linear regression line of tensile strength versus compression

pressure. Therefore a higher value of (Cp) means that with increasing compression pressure the

tensile strength of the compact increases faster in comparison to materials with lower (Cp). [13]

Compactibility of the materials is accessed by compactibility coefficients (Cp) which are

presented in table 8.

According to (Cp) the compactibility of excipients decreases in the following order for direct

compression: Avicel PH 200>DCL 21>TCP>Avicel PH 102for Dry granulation:

TCP>DCPD>LM>MCC IP.

Table 8: Compactibility co-efficient (Cp) of excipients studied

Batch No Excipient Cp* 101 R2

SAT 3 (DC) Avicel PH 102 (DC) 7.11 0.996

SAT 6 (DC) Avicel PH 200 (DC) 8 0.994

SAT 9 (DC) DCL 21 (DC) 7.8 0.996

SAT 21 (DC) TCP (DC) 7.23 0.993

SATD 1 (DG) MCC IP (DG) 6.06 0.984

SATD 2 (DG) LM (DG) 6.38 0.989

SATD 3 (DG) DCPD (DG) 6.84 0.994

SATD 4 (DG) TCP (DG) 7.6 0.997

0

200

400

600

0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4 0.45 0.5

Spec

ific

vo

lum

e

log P

Comparision of Walker analysis(Sarpagandha Dry granulation)

MCC IP DCPD TCP LM

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Figure 5: Compactibility profile of excipients

Kawakita’s equation

Table 9: Values of 1/a, a/ab, a and b for various excipient

Avicel

PH 102

Avicel

PH 200

DCL

21

TCP MCC

IP

LM DCPD TCP

1/a 4.616 5.126 1.976 1.909 2.775 2.488 2.463 3.113

1/ab 44.23 13.19 14.216 15.026 7.68 4.34 14.29 4.34

a 0.217 0.195 0.506 0.5248 0.360 0.402 0.406 0.321

b 0.104 0.388 0.140 0.127 0.361 0.573 0.172 0.718

*Slope = 1/a Intercept = 1/ab

The packability of agglomerates of the tableting mixture was ascertained by comparing the

constants a, b and k in Kawakita’s and Kuno’s equations, respectively. The constant ‘a’

represents the proportion of consolidation as closest packing is attained. The reciprocal of b and

k represents the packing velocity. The constant ‘a’ for the direct compression tableting mixture

containing Avicel PH 200 has smaller value than the others and for dry granulation TCP has

smaller value than other two excipients.[14] The results indicate that the agglomerates showed

good packing even without tapping. The large value of b for the direct compression of Avicel PH

200 and for the dry granulation Tproved that the packing velocity of these excipient and drug by

tapping was slower than that of the other excipients.

0

0.5

1

1.5

2

2.5

0 0.5 1 1.5 2 2.5 3 3.5

Ten

sile

str

engt

h (

TON

)

Compression pressure (TON)

MCC102 MCC 200 DCL TCP

MCC IP Lactose monohydrate DCPD TCP

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Kuno’s equation

Table 10: values of k for different excipient

Avicel

PH 102

Avicel

PH 200

DCL 21 TCP MCC IP LM DCPD TCP

k 0.01 0.006 0.001 0.009 0.05 0.07 0.02 0.01

The values of ‘k’ from kuno’s equation for the tableting mixtures were shown in table 10. The

slow packing velocity corresponds with proportion of the consolidation of the powder bed per

tap. The Avicel PH 200 for direct compression and TCP for dry granulation showed comparable

compression properties as compared with other excipients.

Elastic recovery

Plasticity and fragmentation are desirable deformational properties for compaction. On the other

hand, elastic deformation is undesirable because it hinders the formation of coherent tablets.

Fragmentation and plastic deformation are considered to be strength-producing compression

mechanisms whereas elastic deformation is considered to be a disruptive rather than bond-

forming mechanism. Fragmentation is suggested to increase the strength by the large number of

contact sites between particles at which bonds can be formed. For plastic deformation, the

increased bonding force is usually explained as an effect of increased contact area at the

interparticulate contact site. Plasticity is more expressed in the case of mixture of Avicel PH 200

for direct compression and TCP for dry granulation. It can be assumed that the material is brittle

with minimal plasticity.

The elastic deformation results expressed as an index of elastic relaxation are presented in table

11. For the directly compressible tableting mixture, elasticity decreases in following order:

tableting mixture containing Avicel PH 200>TCP>DCL 21>Avicel PH 102, and for dry

granulation method TCP>LM>MCC>LM. According to Py value, the material is considered soft

when the value is below 0.92 ton, moderately hard when the value is between 0.93 and 2.30 ton

and hard when the value is higher than the 2.30 ton.[13] Therefore elastic relaxation index were

used to describe materials deformational properties. The results are summarized in table 12.

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Table 11: Elastic relaxation for excipient studied

Batch No Drug + Excipient Elastic recovery (%)

AVG SD

SAT 3 (DC) Avicel PH 102 0.74 0.09

SAT 6 (DC) Avicel PH 200 0.21 0.06

SAT 9 (DC) DCL 21 0.37 0.05

SAT 21 (DC) TCP 0.24 0.10

SATD 1 (DG) MCC IP 0.22 0.06

SATD 2 (DG) LM 0.21 0.07

SATD 3 (DG) DCPD 0.33 0.04

SATD 4 (DG) TCP 0.19 0.03

Table 12: Assessment of the deformational properties of tableting mixture determined as

the bulk level using yield pressure (Py), obtained from the Heckel co-efficient and elastic

relaxation

Batch No Excipient Py (ton) Plasticity ER Elasticity

SAT 3 (DC) MCC 102 (DC) 0.9904 Moderately soft 0.74 0.09 Medium

SAT 6 (DC) MCC 200 (DC) 0.6736 Soft 0.21 0.06 High

SAT 9 (DC) DCL 21 (DC) 0.9985 Moderately soft 0.37 0.05 Medium

SAT 21 (DC) TCP (DC) 1.0936 Moderately soft 0.24 0.10 Medium

SATD 1 (DG) MCC IP (DG) 0.8420 Soft 0.22 0.06 High

SATD 2 (DG) LM (DG) 0.9542 Moderately soft 0.21 0.07 Medium

SATD 3 (DG) DCPD (DG) 1.1403 Moderately soft 0.33 0.04 Medium

SATD 4 (DG) TCP (DG) 0.7101 soft 0.19 0.03 High

CONCLUSION

Various excipients have a great influence on the compressibility and compactibility process. In

order to determine best excipient for the drug, tableting mixture containing drug with excipient

was precisely characterized. For, direct compression method the most compressible excipient for

preparation of sarpagandha tablet was found to be mixture of Avicel PH 200 and for dry

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granulation it was TCP. Further, tableting mixtures containing these excipients showed good

flow properties along with acceptable hardness and disintegration time. Both, the Heckel plots

and walker analysis showed the same result. Kawakita’s and kuno’s equation showed that these

tableting mixtures has smaller value of ‘a’ and large value of ‘b’, than other tableting mixtures

indicating that, they can be easily compacted without the tapping.

ACKNOWLEDGMENT

We are thankful to Intas Pharmaceuticals Ltd; Ahmedabad for sending us gift samples of directly

compressible lactose (DCL 21), starch-1500, microcrystalline cellulose (Avicel PH-102, Avicel

PH-200).

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