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469 | P a g e International Standard Serial Number (ISSN): 2319-8141

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International Journal of Universal Pharmacy and Bio Sciences 2(5): September-October 2013

INTERNATIONAL JOURNAL OF UNIVERSAL

PHARMACY AND BIO SCIENCES IMPACT FACTOR 1.89***

ICV 3.00***

Pharmaceutical Sciences RESEARCH ARTICLE……!!!

FORMULATION DESIGN AND INVITRO EVALUATION OF EXTENDED RELEASE

TABLETS OF KETOROLAC-USING EUDRAGIT POLYMERS

Y.Ganesh Kumar1*, B.Divya

1, P.Nithin Kumar

2, J.Sreekanth

3, D.Satyavati

4

1Research Scholar, Faculty of Pharmaceutical Sciences, JNTU Hyderabad, A.P.

2Vikas College of Pharmacy, Shameerpet, Jangaon, Warangal, A.P, India.

3MSN Laboratories Ltd, Hyderabad, Andhra Pradesh, India

4Sree Dattha Institute of Pharmacy, Sheriguda, Ibrahimpatnam, R.R Dist, A.P.

KEYWORDS:

Ketorolac tromethamine,

Extended Release,

Eudragit.

For Correspondence:

Y.Ganesh Kumar *

Address:

Research Scholar,

Faculty of

Pharmaceutical Sciences,

JNTU Hyderabad.

Email-ID:

[email protected]

ABSTRACT

Ketorolac is an NSAID. It is indicated for short term management of

moderate to moderately severe acute pain, including post surgical

pain, acute musculoskeletal trauma pain and post partum uterine

cramping pain. The biological half life of ketorolac is 3-6 hrs; hence

lower doses of ketorolac are required as loading dose and higher

doses as maintenance dose. Therefore, it is considered as a suitable

drug for the formulation of extended release tablets to prolong its

therapeutic action. In the Present work, studies were carried on the

preparation and evaluation of Extended release tablets of ketorolac

using hydrophilic swellable polymers Eudragit (RSPO,L100,S100)

with a view to obtain sustain release characteristic to achieve

prolonged therapeutic effect by continuously releasing medication

over a extended period of time after administration of single dose.

The dissolution result shows that an increased amount of polymer

resulted in retarded drug release. A concentration dependent drug

release is evident in case of the polymer i.e., lower concentration of

polymers, release is marginally retarded at higher concentration is

considerable. Our prepared Extended release formulation containing

Combination of Eudragit(S100,L100)15 % is probably showing

better release based on 80 –90 % drug release within 8 -9 hours,

which is the average G.I. residence time.

mailto:[email protected]



- 470 - | P a g e International Standard Serial Number (ISSN): 2319-8141


INTRODUCTION:

Most conventional oral drug products, such as tablets and capsules are formulated to release the

active drug immediately after oral administration, to obtain rapid and complete systemic drug

absorption. Such immediate-release products result in relatively rapid drug absorption and onset of

accompanying pharmacodynamic effects. However, after absorption of the drug from the dosage

form is complete, plasma drug concentrations decline according to the drug's pharmacokinetic

profile. Eventually, plasma drug concentrations fall below the minimum effective plasma

concentration (MEC), resulting in loss of therapeutic activity. Before this point is reached, another

dose is usually given if a sustained therapeutic effect is desired. An alternative to administering

another dose is to use a dosage form that will provide sustained drug release, and therefore maintain

plasma drug concentrations, beyond what is typically seen using immediate-release dosage forms.

(1)Various types of modified release formulations have been developed to improve the patient

compliance and also clinical efficacy of the drug. The extended release oral dosage forms have been

demonstrated to improve therapeutic efficacy by maintaining steady state drug plasma concentration

(2). Eudragit polymers have been widely studied for their application in oral extended release

formulations. Such hydrophilic polymers are most popular because of their flexibility to get a

desirable drug release profile, cost effectiveness and broad regulatory Eudragit most widely used as

the gel forming agent in the formulations of solid, liquid, semisolid and controlled release dosage

forms. (3, 4)

MATERIALS AND METHODS:

Ketorolac was obtained from Bright labs, Hyderabad. Eudragit grades were received as gift samples

from Baris Pharmaceuticals Pvt. Ltd., Hyderabad. Other materials were purchased from yarrow

chem. products, Mumbai, India.

RESULTS:

Methodology:

Preformulation Studies:

Standardization of Ketorolac by UV-Visible Spectrophotometer:

In 0.1 N Hcl Solution:

Preparation of stock solution: Stock solution 100µg/ml of Ketorolac was prepared in 0.1N Hcl

solution. This solution was approximately diluted with 0.1N Hcl to obtain a concentration of

10µg/ml. The resultant solution was scanned in range of 200- 400nm using UV double beam

spectrophotometer (Lab India UV-3000+)



Fig: 1) Lambda Max of Ketorolac in 0.1 N Hcl (316nm)

ii) Standard calibration of Ketorolac in 0.1N Hcl:

100mg of Ketorolac was accurately weighed and dissolved in100ml of 0.1N Hcl to obtain a

concentration of 1000µg/ml. From the above 10ml was withdrawn and diluted to 100ml to obtain a

concentration of 100µg/ml. From this stock solution aliquots of 0.2ml, 1ml, 1.5ml, 2ml and 2.5ml

were diluted in 10ml volumetric flask with phosphate buffer to give concentrations in range of

2µg/ml to 25µg/ml respectively, absorbance was measured at 316nm.

Standard graph of Ketorolac in 0.1 N Hcl:

S.No Concentration (mcg/ml) Absorbance

1 0 0.000

2 2 0.119

3 4 0.229

4 6 0.364

5 8 0.470

6 10 0.568

7 15 0.790

8 20 1.069

Table 1: Standard graph of Ketorolac in 0.1 N Hcl



Fig 2: Standard graph of Ketorolac in 0.1 N Hcl

In pH 6.8 Buffer:

Preparation of stock solution: Stock solution 100µg/ml of Ketorolac was prepared in phosphate

buffer of pH 6.8. This solution was approximately diluted with phosphate buffer of pH 6.8 to obtain

a concentration of 10µg/ml. The resultant solution was scanned in range of 200- 400nm using UV

double beam spectrophotometer (Lab India UV-3000+)

Fig 3: Lambda Max of Ketorolac in pH 6.8 Buffer (322 nm)

Standard calibration of ketorolac in phosphate buffer of pH 6.8:

100mg of ketorolac was accurately weighed and dissolved in100ml of pH 6.8 phosphate buffer to

obtain a concentration of 1000µg/ml. From the above 10ml was withdrawn and diluted to 100ml to

obtain a concentration of 100µg/ml. From this stock solution aliquots of 0.5ml, 1ml, 1.5ml, 2ml and

2.5ml were diluted in 10ml volumetric flask with phosphate buffer to give concentrations in range of

5µg/ml to 25µg/ml respectively, absorbance was measured at 322nm.



Table 2: Standard graph of Ketorolac in pH 6.8 Buffer:

S.No Concentration (mcg/ml) Absorbance

1 0 0.000

2 2 0.197

3 4 0.395

4 6 0.583

5 8 0.772

6 10 0.954

7 12 1.151

8 14 1.345

Fig 4: Standard graph of Ketorolac in pH 6.8 Buffer

Drug- Excipient Compatibility by FTIR studies:

In the preparation of ER Tablet, drug and polymer may interact as they are in close contact with

each other, which could lead to instability of drug. Preformulation studies regarding drug-polymer

interactions are therefore very critical in selecting appropriate polymers. FT-IR spectroscopy was

employed to ascertain the compatibility between Ketorolac and selected polymers. The individual

drug and drug with excipients were scanned separately.



Procedure: Potassium bromide was mixed with drug and polymer in the ratio of 100:1 and pellet

was prepared using KBr pellet press (HORIZON WC-56) and spectrum was taken using FTIR. FT-

IR spectrum of Ketorolac was compared with spectrum of ketorolac and polymer. Disappearance of

Ketorolac peaks or shifting of peak in any of the spectra was studied.

Fig 5: FTIR Spectrum of Pure Drug

Fig 6: FTIR Spectrum of Optimized Formulation

Drug: Excipient Compatibility studies- FTIR:

Drug-Excipient compatibility studies by FTIR revealed no interaction between drug and the

polymers used in the formulation thus showing compatibility.

Angle of repose:

The angle of repose of blends was determined by the funnel method. The accurately weighed blend

was taken in funnel. The height of the funnel was adjusted in such a way that the tip of the funnel

just touched the apex of the heap of the blend. The blend was allowed to flow from the funnel on the

surface. The diameter and height of the heap formed from the blend was measured. The angle of

repose was calculated using following formula

Tan Ѳ= h/r ………… Eqn.(1)

Where, “h” is height of the heap and “r” is the radius of the heap of granules.

3340.530 149.1081592.938 199.099

1545.621 46.128

1492.065 84.620

1468.018 122.392

1378.463 490.199

1274.578 424.215

1045.580 170.856

895.378 78.338

723.810 235.477

590.620 58.229

496.374 132.983

KETOROLAC

3800 3600 3400 3200 3000 2800 2600 2400 2200 2000 1800 1600 1400 1200 1000 800 600 400 200

95

90

85

80

75

70

65

60

55

50

Wavenumber

%T

ransm

itta

nce

1594.665 63.806

1557.977 -0.027

1533.380 25.693

1492.068 19.213

1309.317 13.955

1275.296 92.285

1046.316 19.253

926.916 37.049

420.996 6.154

415.196 3.936

OPTIMIZED FORMULATION

3800 3600 3400 3200 3000 2800 2600 2400 2200 2000 1800 1600 1400 1200 1000 800 600 400 200

100

98

96

94

92

90

88

86

Wavenumber

%T

ransm

itta

nce



Carr’s compressibility index:

The Carr’s compressibility Index was calculated from Bulk density and tapped density of the blend.

A quantity of 2g of blend from each formulation, filled into a 10mL of measuring cylinder. Initial

bulk volume was measured, and cylinder was allowed to tap from the height of 2.5cm. The tapped

frequency was 25±2 per min to measure the tapped volume of the blend. The bulk density and

tapped density were calculated by using the bulk volume and tapped volume.

Carr’s compressibility index was calculated by using following formula:

Carr’s compressibility index (%) =

[(Tapped density-Bulk density) X100]/Tapped density ….. Eqn. (2)

Pre compression Parameters:

Formulation

No

Angle of

repose (Ө)

Bulk density

(gm/cm3)

Tapped

density(gm/cm3)

Carr’s index

(%)

F1 17 0.5076 0.5696 14.89

F2 21 0.5202 0.5452 15.99

F3 19 0.5192 0.5765 14.11

F4 16 0.5029 0.5947 15.77

F5 31 0.5181 0.6026 18.31

F6 17 0.5092 0.5459 19.35

F7 27 0.5147 0.5444 16.79

F8 22 0.5344 0.6881 16.32

F9 14 0.5019 0.5024 15.84

Table 3: Pre Compression Parameters

Post Compression Parameters:

Table 4: Post Compression parameters

Preparation of tablets: Different tablets formulations were prepared by Wet Granulation

technique. All ingredients were weighed. Required quantities of drug, diluents and polymers were

Formulation

No

Weight

variation (mg)

Hardness

(kg/cm2)

Thickness

(mm)

Friability

(%)

Assay

(%)

F1 298 ± 1.91 4.4 ± 0.4 3.63 0.35 97.34

F2 300 ± 1.72 4.8 ± 0.1 3.92 0.29 96.78

F3 298.9 ± 1.08 4.9 ± 0.3 3.98 0.38 98.71

F4 300.2 ± 4.2 4.5 ± 0.2 3.72 0.32 98.50

F5 300.6± 1.43 4.9 ± 0.9 3.82 0.31 96.09

F6 299.5± 1.95 4.2 ± 0.7 3.56 0.21 97.38

F7 299.7± 1.35 4.7± 0.5 3.47 0.19 98.99

F8 300.5 ± 1.28 4.5 ± 0.4 3.43 0.30 99.57

F9 300.0± 1.19 4.8± 0.3 3.79 0.35 99.48



mixed thoroughly with sufficient quantity of binder was added to get the slurry. Then passed

through the 60 mesh sieve. These granules are placed in hot air oven for 15min for evaporating of

unusual binding agent. Then Magnesium stearate was added as lubricant. Aerosil was used as

glidant to the granules shake well, passed through the 40mes sieve. Finally the powder mix was

subjected to compression after mixing uniformly in a polybag. Prior to compression, the blends were

evaluated for several tests. In all formulations, the amount of the active ingredient is equivalent to

30mg of Ketorolac (Table5)

Table 5: Formulation Chart

S.No Ingredient F1 F2 F3 F4 F5 F6 F7 F8 F9

1 ketorolac 30 30 30 30 30 30 30 30 30

2 Eudrgit(RSPO) 30 15 30 - - - 30 - -

3 Eudragit L100 30 15 - 15 30 15 - 30 -

4 Eudragit S100 - - 30 15 30 15 - - 30

5 PVP QS QS QS QS QS QS QS QS QS

6 Mg.Stearate 6 6 6 6 6 6 6 6 6

7 Aerosil 6 6 6 6 6 6 6 6 6

8 MCC Qs Qs Qs Qs Qs Qs Qs Qs Qs

Total weight 300 300 300 300 300 300 300 300 300

Evaluation of tablets:

The weight of tablets was evaluated on 20 tablets using an electronic balance. Friability was

determined using 6 tablets in Roche friability tester at 25rpm. Hardness of the tablets was evaluated

using a Monsanto hardness tester. The hardness of all the formulation was between 4-5 kg/cm2.

In vitro dissolution studies:

In vitro drug release studies from the prepared matrix tablets were conducted using USP type II

apparatus at 37°C at 50rpm. Dissolution mediums used were 900mL of 0.1N HCl and phosphate

buffer of pH 6.8. The release rates from matrix tablets were conducted in HCl solution (pH 1.2) for

2h and changed to phosphate buffer (pH 6.8) for further time periods. The samples were withdrawn

at desired time periods from dissolution media and the same were replaced with fresh dissolution

media of respective pH. The samples were analyzed by UV-Visible Spectrophotometer (Lab India

3000+). The amounts of drug present in the samples were calculated with the help of appropriate

calibration curves constructed from reference standards. Drug dissolved at specified time periods

was plotted as percent release versus time curve. (5, 6, 7)

Dependent-model method (Data analysis):

In order to describe the losartan potassium release kinetics from individual tablet formulations, the

corresponding dissolution data were fitted in various kinetic dissolution models: zero order, first



order, Higuchi, Korsmeyer Peppas. When these models are used and analyzed in the preparation, the

rate constant obtained from these models is an apparent rate constant. The release of drugs from the

matrix tablets can be analyzed by release kinetic theories. To study the kinetics of drug release from

matrix system, the release data were fitted into Zero order as cumulative amount of drug release vs.

time (Eqn.3), first order as log cumulative percentage of drug remaining vs. time (Eqn.4), Higuchi

model as cumulative percent drug release vs. square root of time (Eqn.5). To describe the release

behavior from the polymeric systems, data were fitted according to well known exponential

Korsmeyer – Peppas equation as log cumulative percent drug release vs. log of time equation

(Eqn.6).

(i) Zero order kinetics

Qt=K0t……………………………Eqn. (3)

Where,

Q= Amount of drug release in time t

K0 = Zero order rate constant expressed in unit of concentration /time

t = Release time

(ii) First order kinetics

Log Q=Log Q0-kt/2.303…………Eqn. (4)

Where,

Q0= is the initial concentration of drug

k= is the first order rate constant

t =release time

(iii) Higuchi kinetics

Q=kt1/2………………………...…Eqn. (5)

Where,

k= Release rate constant

t=release time, Hence the release rate is proportional to the reciprocal of the square root of time.

(iv) Korsmeyer-Peppas

First 60% in vitro release data was fitted in equation of Korsmeyer et al. to determine the release

behavior from controlled release polymer matrix system. The equation is also called as power law,

Mt /M∞ =Kt n …………………… Eqn. (6)

Where,

Mt = amount of drug released at time t

M∞ = amount of drug released after infinite time

Mt /M∞ = fraction solute release

t = release time

K = kinetic constant incorporating structural and geometric characteristics of the polymer system

n = diffusional exponent that characterizes the mechanism of the release of traces. The magnitude of

the release exponent “n” indicates the release mechanism (i.e. Fickian diffusion, Non Fickian,



supercase II release). For matrix tablets, values of n of near 0.5 indicates Fickian diffusion

controlled drug release, and an n value of near 1.0 indicates erosion or relaxational control (case II

relaxational release transport, non Fickian, zero order release). Values of n between 0.5 and 1

regarded as an indicator of both diffusion and erosion as overall release mechanism

Commonly called as anomalous release mechanism. (8-16)

In vitro dissolution studies:

Table 6: Dissolution release profiles of Formulations F1-F9

Fig 7: Dissolution profiles of Formulations F1-F3 (Using Eudrgit (RSPO), Eudragit L100).

0

10

20

30

40

50

60

70

80

90

0 2 4 6 8 10 12

% Drug Release Of F1



Time

% D

rug

Re

leas

e

F1-F3

Time

(hours)

Dissolutio

n medium

%

Drug

releas

e

Of F1

%

Drug

release

Of F2

%

Drug

release

Of F3

%

Drug

release

Of F4

%

Drug

release

Of F5

%

Drug

release

Of F6

%

Drug

release

Of F7

%

Drug

release

Of F8

%

Drug

release

Of F9

0

0.1 N

HCl

0 0 0 0 0 0 0 0 0

0.5 0.45 0.16 0.69 1.56 1.44 3.59 4.00 0.45 0.05

1 1.38 1.27 1.85 3.47 2.31 7.88 5.21 1.84 1.21

2 2.06 2.66 4.40 7.07 2.83 14.79 6.71 3.41 2.89

3

Ph 6.8

Phosphate

Buffer

11.06 9.43 17.17 31.10 11.56 40.03 26.19 25.98 22.96

4 20.82 16.32 31.66 48.53 20.88 55.42 44.07 42.79 38.09

5 30.05 23.15 42.41 59.28 30.39 67.35 53.46 57.82 47.38

6 43.39 30.17 53.76 67.66 43.22 75.85 62.78 71.72 71.80

7 47.64 36.74 59.12 69.47 50.77 83.01 66.41 74.69 75.66

8 57.24 43.20 64.40 76.13 59.17 86.79 89.87 91.03 86.94

9 63.72 49.76 70.40 79.07 67.87 93.27 97.30 104.57 95.99

10 75.60 54.20 76.54 85.07 80.83 98.31 ___ ___ ___



Fig 8: Dissolution profiles of Formulations F4-F6 (Using Eudragit L100, S 100).

Fig 9: Dissolution profiles of Formulations F7-F9 (Using Eudrgit (RSPO),

Eudragit L100, S 100)

Kinetics of In-vitro Drug Release:

The drug diffusion through most type of polymeric system is often best described by Fickian

diffusion (diffusion exponent, n=0.5), but other process in addition to diffusion are important. There

is also a relaxation of the polymer chain, which influences the drug release mechanism. This process

is described as non- fickian or anomalous diffusion (n=0.5-1.0). Release from initially dry,

hydrophilic glassy polymer that swell when added to water and become rubbery, show anomalous

diffusion as a result of the rearrangement of macromolecular chain. The thermodynamics state of the

polymer and penetrant concentration are responsible for the different type of the diffusion. A third

0

20

40

60

80

100

120

0 2 4 6 8 10 12




% D

rug

Re

leas

e

Time

F4-F6

0

20

40

60

80

100

120

0 2 4 6 8 10




% D

rug

Rel

ease

Time

F7-F9



class of diffusion is case-II diffusion (n=1), which is a special case of non- Fickian diffusion. To

obtain kinetic parameter of dissolution profile, data were fitted to different kinetic model

Table 7: Different kinetic models for Ketorolac ER matrix tablets (F1 to F9)

Code Zero order First order Higuchi Peppas Best fit model

R2 K0

mg/h−1

R2 K1 (h

−1) R

2 K

(mg h−1/2

)

R2 n

F1 0.9474 10.063 0.8592 0.1938 0.8334 23.8548 0.9830 1.9166 Peppas

F2 0.9700 9.4137 0.9021 0.1766 0.8712 23.6698 0.9656 1.7465 Zero-order

F3 0.9820 8.2020 0.9157 0.1455 0.8820 21.6151 0.9781 1.5340 Zero-order

F4 0.8785 10.209 0.7772 0.1920 0.8285 24.6881 0.7632 1.2412 Zero-order

F5 0.9664 9.1268 0.9041 0.1668 0.8594 22.8722 0.9841 1.7415 Peppas

F6 0.9724 4.6413 0.9471 2.0504 0.8364 13.945 0.9798 1.4375 Zero-order

F7 0.9699 8.3884 0.9632 0.1422 0.9049 22.3442 0.9419 1.4277 Zero-order

F8 0.9757 8.6500 0.9669 0.1507 0.9154 23.0754 0.9460 1.3418 Zero-order

F9 0.9641 8.1897 0.9469 0.1388 0.8782 21.6680 0.9519 1.6487 Zero-order



Fig 10: Kinetic Model (Zero Order)

Fig 11: Kinetic Model (Highuchi)

y = 0.238x - 4.641R² = 0.972

-10

0

10

20

30

40

50

60

70

80

0 100 200 300 400

Cu

mu

lati

ve %

dru

g r

ela

se

time

Zero Order

ZERO ORDER

y = 4.071x - 13.94R² = 0.836

-20

-10

0

10

20

30

40

50

60

70

80

0 5 10 15 20

Cu

mu

lati

ve %

dru

g r

ele

ase

Root Time

Higuchi

HIGUCHI



Fig 12: Kinetic Model (Peppas)

Fig 13: Kinetic Model(First Ordder)

y = 1.319x - 1.437R² = 0.979

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2

0 0.5 1 1.5 2 2.5 3

Lo

g C

um

ula

tive %

dru

g r

ele

ase

Log Time

Peppas

pep…Line…

y = -0.001x + 2.050R² = 0.947

0.000

0.500

1.000

1.500

2.000

2.500

0 50 100 150 200 250 300 350

Lo

g %

dru

g r

em

ain

ing

time

First Order

first order



DISCUSSION:

Preformulation characteristics:

The drug ketorolac was standardized by UV method in 0.1N Hcl and pH 6.8 Buffer separately. The

lamba max were 316nm and 322 nm in 0.1N Hcl and pH 6.8 buffer respectively and the linearity

range was 5-25 mcg/ml in both the media.

Physical characteristics of blends and tablets:

The blends of different formulations were evaluated for angle of repose, Carr’s compressibility

index etc., (Table 3). The results of Angle of repose and Carr’s compressibility Index (%) ranged

from 16-28 and 14-16, respectively which showed that blends from all the formulations having good

flow property. The hardness and percentage friability ranged from 4-5kg/cm2 and 0.18-0.35%

respectively. Ketorolac is a water soluble drug its release from the matrix is largely dependent on the

polymer swelling, drug diffusion and matrix erosion. The concentration of polymer in the sustained

release tablet was a key factor in controlling the drug release.

Various Extended release formulations were formulated with HPMC K100M, Eudragit (RSPO,

L100, and S100) polymer alone; polyvinyl pyrolidone as binder and microcrystalline cellulose was

used as diluents. When cumulative % drug release plotted versus time, it was observed that, for three

of the polymers used, an increase in polymer concentration induce a decrease in the release rate.

CONCLUSION:

The experimental findings can be summarized as follows:

1. IR spectra indicated the absence of probable chemical interaction between the drug and polymers

used in three different proportions.

2. In-vitro dissolution studies showed that tablets of ketorolac in 1:2 proportion, prepared by wet

granulation is the best to increase sustain effect due to increase in the polymer concentration.

3. The extent of drug release decreased with an increase in polymeric content of matrix in the

following order: 1:1 > 1:1.5 > 1:2.

4. Hence it is concluded that tablets of Ketorolac prepared by wet granulation is the best to increase

the sustain action with Eudragit (RSPO, L-100, S-100) polymer in the concentration of 1:2 i.e., drug

to polymer ratio.The extended release tablets of ketorolac were prepared successfully using Eudragit

polymer of different viscosity. According to in vitro release studies, the release rate was decreased

with increasing viscosity and amount of polymer. The results of the study clearly demonstrated that

Eudragit Extended tablet formulation is an effective and promising drug delivery system for once

daily administration of Ketorolac. The analysis of the release profiles in the light of distinct kinetic

models (zero order, first order, Higuchi, Korsmeyer Peppas) led to the conclusion that, the drug



release characteristics from ketorolac polymer matrices follows Higuchi square root time kinetics

and the mechanism of drug release was both diffusion and erosion.

Acknowledgement:

The authors are thankful for the management of MSN Laboratories Ltd, Hyderabad, Bright Labs,

Hyderabad and Baris Pharmaceuticals Pvt Ltd, Hyderabad for the gift samples of drug and polymers

used in the work.

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