Design Optimization and Evaluation of pH Responsive ... · Design Optimization and Evaluation of pH...

Article ID: WMC00830 2046-1690

Design Optimization and Evaluation of pHResponsive Prednisolone Sustained Release Tabletfor Ileo-colonic DeliveryCorresponding Author:Dr. Rakesh Patel,Associate Prof & Head, Dept of Pharmaceutics, S. K. Patel College of Pharmaceutical Education & Research,Ganpat University, 382711 - India

Submitting Author:Dr. Rakesh Patel,Associate Prof & Head, Dept of Pharmaceutics, S. K. Patel College of Pharmaceutical Education & Research,Ganpat University, 382711 - India

Article ID: WMC00830

Article Type: Research articles

Submitted on:30-Sep-2010, 08:04:51 AM GMT Published on: 30-Sep-2010, 03:25:20 PM GMT

Article URL: http://www.webmedcentral.com/article_view/830

Subject Categories:PHARMACEUTICAL SCIENCES

Keywords:Prednisolone, Eudragit polymers, Colon targeting, Inflammatory bowel diseases

How to cite the article:Patel R , Patel H , Baria A . Design Optimization and Evaluation of pH ResponsivePrednisolone Sustained Release Tablet for Ileo-colonic Delivery . WebmedCentral PHARMACEUTICALSCIENCES 2010;1(9):WMC00830

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Design Optimization and Evaluation of pHResponsive Prednisolone Sustained Release Tabletfor Ileo-colonic DeliveryAuthor(s): Patel R , Patel H , Baria A

Abstract

The focus of this work is to provide accurate andeffective treatment of inflammatory bowel disorderslike ulcerative colitis. The necessity and advantages ofcolon-specific drug delivery systems have been wellrecognized and documented. Generally, the singleapproaches to obtain colon-specific delivery achievedlimited success. So new combined oral drug deliverysystem for colon targeting of Prednisolone wasdeveloped which contains sustained drug releasesystem of hydroxypropylmethylcellulose, ethylcellulose, pectin, starch and polymeric coating ofEudragit polymers. DSC, FTIR and acceleratedstability studies indicates no possibility of interactionbetween Prednisolone and other ingredients. Theresults of the in vitro dissolution tests in 1st fluid (pH1.2), 2nd fluid (pH 4.5) and 3rd fluid (pH 7.2) indicatedabsence of drug release in stomach and smallintestine and controlled release in colonic medium upto 8 hrs.

Introduction

The most extensive application of a formulationstrategy for colonic delivery has been the employmentof enteric coatings on solid substrates. This is anatural development of conventional coatingtechnologies to avoid gastric release thus preventingproblems such as degradation, pharmacologicaleffects including gastric irritation and nausea. Theunderlying principle of this approach has beenemployment of polymers that are able to withstand thelower pH values of the stomach, but disintegrate andrelease the drug as the pH in the small bowelincreases. Targeted delivery of drugs to the colon isusually to achieve one or more of four objectives likes(a) To reduce dosing frequency (b) To delay deliveryto the colon to achieve high local concentrations in thetreatment of diseases of the distal gut (c) To delaydelivery to a time appropriate to treat acute phases ofdisease, (d) To deliver to a region that is less hostilemetabolically.Ulcerative colitis is characterized by diffuse mucosal

inflammation limited to the colon. Disease extent canbe broadly divided into distal and more extensivedisease. ‘‘Distal’’ disease refers to colitis confined tothe rectum (proctitis) or rectum and sigmoid colon(proctosigmoiditis). More extensive disease includesleft sided colitis, extensive colitis and pancolitis(affecting the whole colon). Crohn disease andulcerative colitis are chronic relapsing disorders ofunknown origin. These diseases share many commonfeatures and are collectively known as idiopathicinflammatory bowel disease.Prednisolone (PDS), a typical glucocorticoid has beenused for the treatment of inflammatory bowel disorders.However, when PDS is orally administered, a largeamount of the drug is absorbed from uppergastrointestinal tracts and enters into the systemiccirculation. This deteriorates the therapeutic efficacy ofPDS and causes systemic side effects such asadrenosuppression, hypertension and osteoporosis.Therefore, it is preferable for treatment of inflammatorybowel disorders to deliver the drug site-specifically tocolon.Among the various types of cellulose ether derivatives,HPMC polymers are popular in controlled releasematrices due to their compatibility with numerousdrugs. HPMC offers the advantage that, although wetmassing may be used to conventionally granulate thematerial direct compression of the drug blended drugwith HPMC is easily accomplished.The objective of this work was to formulate, optimizeand evaluate sustained release tablet of PDS forileo-colonic delivery. Matrix tablet of PDS wasprepared with pectin, hydroxypropyl methylcellulose,ethyl cellulose and this tablet formulation is coatedwith eudragit polymer to prevent drug release in uppergastrointestinal tract and improve therapeutic effect fortreatment of inflammatory bowel disorder.

Methods

MaterialsPrednisolone (PDS) was received as gift sample fromLincoln Pharmaceuticals Ltd, Ahmedabad. Starch wasreceived from Shital Chemicals Ltd. Hydroxypropylmethylcellulose K-4M (HPMC K-4M), hydroxypropyl



methylcellulose K-100M (HPMC K-100M) and ethylcellulose were received from Ranchem Ltd, Mumbai.Eudragit FS 30D was received from Corel Pharma Ltd,Ahmedabad. All other chemical and reagent were ofanalytical grade and used as received.Methods1) Drug-Excipients Interaction studiesAssessment of possible incompatibilities between anactive drug substance and different excipients formsan important part of the preformulation stage duringthe development of solid dosage form.DifferentialScanning Calorimeter (DSC) allows the fast Evaluationof possible incompatibilities, because it showschanges in the appearance, Shift of meltingendotherms and exotherms, and/or variations in thecorresponding enthalpies of reaction DSCthermograms of pure drug (PDS), HPMC K-4M andHPMC K-100M, Ethyl cellulose, Starch were taken fortheir identical endothermic reaction. Finally physicalmixture of all above ingredients was scanned for DSC.The thermal analysis was performed in a nitrogenatmosphere at a heating rate of 10°C/min over atemperature range of 50°C to 300°C.2) Preparation of tabletsThe tablets were prepared by wet granulationtechnique. Drug, polymers and diluent were passedthrough 60 # sieve and then dry blend of drug,polymer and diluent were granulated with starch paste.The mass was dried at 50°C for about 30 min andsized through 22 # sieve. Finally, weighed quantity ofmagnesium stearate, aerosil and talc were mixedglidant and lubricant and then tablet blend wascompressed on Rotary tablet compression machine(CMB4 -12 stations).3) Full factorial designA 32 randomized full factorial design was used in thisstudy. In this design 2 factors were evaluated, each at3 levels, and experimental trials were performed at all9 possible combinations. The amounts of HPMC K-4M(X1) and EC (X2) were selected as independentvariables. Percentage release of drug for 1st hour (Q1)and 8th hour (Q8) were selected as dependentvariables.4) Evaluation of tablet blends4.1 Angle of ReposeThe fixed funnel and free-standing cone methodsemploy a funnel that is secured with its tip at givenheight, H, which was kept 2 cm, above graph paperthat is placed on a flat horizontal surface. With R,being the radius of base of conical pile, angle ofrepose can be determined using following equation:

…………………. (1)

4.2 Bulk density and Tapped density

Density is a term obtained by dividing weight ofpowder by volume of powder. It is given as g/cm3. Bulkdensity (ρB) is determined by the bulk volume and theweight of dry powder in a graduated cylinder. Bulkvolume of powder is sum of tapped volume plus voidvolume. Void volume is eliminated by tapping thegraduated cylinder on flat horizontal surface fromconstant height and by constant force for 4000 times.This tapped volume gives the tapped density (ρT).Theequations are as following:

……………….. (2)

.………………. (3)

Where W is the weight of dry blend, VB is the bulk oruntapped volume, VT is the tapped volume.

4.3 Compressibility Index

Compressibility index (Carr’s index) gives theimportant property of granules. It can be calculated byfollowing equation:

………………. (4)

5) Evaluation of tablets

Prepared tablets were evaluated for certain physicalproperties like uniformity of weight, hardness, friabilityand dissolution study etc.

5.1 Uniformity of weight

Every individual tablet in a batch should be in uniformweight and weight variation in within permissible limits.The weights were determined to within ±1mg by usingSartorious balance (BT 124 S). Weight control isbased on a sample of 20 tablets.

5.2 Dimensions

The dimensions (diameter and thickness) were thendetermined to within ± 0.01 mm by using digital verniercalipers.

5.3 Hardness

The hardness of the tablets was determined bydiametric compression using a Hardness testingapparatus (Monsanto Type). A tablet hardness ofabout 4-5 kg is considered adequate for mechanicalstability. Determinations were made in triplicate.

5.4 Friability

The friability of the tablets was measured in a Rochefriabilator (Camp-bell Electronics, Mumbai). Tablets ofa known weight (W0) or a sample of 400 tablets arededusted in a drum for a fixed time (4000 revolutions)and weighed (W) again. Percentage friability wascalculated from the loss in weight as given in equationas below. The weight loss should not be more than 1%.



..……………… (5)

5.5 In-vitro dissolution studyThe release rate of PDS matrix tablet was determinedusing United State Pharmacopoeia (USP) XXIVdissolution testing apparatus II (paddle method). Thedissolution test was performed using 900 ml ofphosphate buffer (PH=7.2), at 37 ± 0.5 °C and 100rpm. A sample (10 ml) of the solution was withdrawnfrom the dissolution apparatus at 1, 2, 4, and 8 hour.The samples were replaced with fresh dissolutionmedium of same quantity. The samples were filteredthrough a 0.45 um membrane filter. Absorbance ofthese solutions was measured at 246 nm using a UV –1800; M/s Shimadzu UV/V is double beamspectrophotometer.5.6 Accelerated stability studiesOptimized formulation were packed in blister andstored in ICH certified stability chambers maintained at40°C and 75% RH for three months. The tablets werewithdrawn periodically and evaluated for drug contentand release studies.6. Preparation of Eudragit coating solutionsCoating of PDS sustained release matrix tablet wasdone with Eudragit RS100 solution and Eudragit FS30D solution. Eudragit RS100 solution was preparedby dissolving Eudragit RS100 powder in isopropylalcohol solution, diluted up to concentration of 12.5 %and finally PEG-400 (1.25%) was added as aplasticizer. Eudragit FS 30D solution is available asaqueous dispersion and PEG-400 (1.25%) was usedas plasticizer. About 1000 tablets of PDS sustainedrelease matrix tablet were taken and allow to coatingin pan coater at 50 rpm and 50oC temperature.Coating was carried out with spraying method anddried with same.

Results

a) Differential Scanning Calorimetry (DSC)AnalysisDSC curves obtained for pure PDS, HPMC K-100M,ethyl cellulose, ctarch, pectin and their physicalmixtures are shown in Figure 1 (a) & (b). Purepowdered PDS showed a melting endotherm at241.98°C. DSC scan of PDS with HPMC K-100Mshowed single broad endotherm at 241.23°C, whilePDS and pectin shows peak at 238.15oC and160.66oC. DSC thermo grams of physical mixture ofdrug and excipients showed the melting peak of thedrug at 239.75°C and broad endothermic peak at160.11°C due to melting of HPMC. Physical mixture ofall above ingredients showed their identical peaks at

defined temperature range. Presence of all peaksindicates that all ingredients are compatible with eachother.b) Full factorial designi) Factorial equation for Q1Concerning Q1, the results of multiple linearregression analysis showed that both the coefficientsb1 and b2 bear a negative sign. It is possible that athigher polymers concentration, PDS is trapped insmaller polymer cells and it is structured by its closeproximity to the polymer molecules. So, increasing theamount of the polymer in the formulations increasedthe time it took for the drug to leave the formulationand retard release of drug into the medium.Q1 = 18.45-6.447 X1 -1.281X2 + 0.949 X1X2+0.537X12 – 0.123X22 (R2= 0.9965) …..(6)The Q1 for all the batches F1 to F9 varied from 24.12% to 6.12 % showed good correlation coefficient as0.9965. Results of the equation (2) indicated that boththe concentration of the X1 and X2 were responsiblefor the Q1.ii) Factorial equation for Q8The amount of drug released after 8 hrs is alsoimportant parameters for prominent drug release fromsustained release matrix formulation. The Q8 for allthe batches F1 to F9 varied from 97.23% to 76.38 %.Concerning drug release at 8 hrs (Q8), the results ofmultiple linear regression analysis showed that boththe coefficients b1 and b2 bear a negative sign.Therefore, increasing the concentration of eitherHPMC K4M or EC is expected to decrease the drugrelease. Such delay in drug release may be becauseof the release rate is conditioned by the concentrationof the polymer. The fitted equation relating theresponse Q8Hrs (Y) to the transformed factor is shownin following equation,Q8 = 68.98- 10.21X1 -5.67X2 +1.167 X1X2+0.0145X12+ 2.389 X22 (R2= 0.987) ……. (7)From the results of the equation (3) it was concludedthat the effect of the concentration of HPMC K4M (X1)was very high and in minus sign while the effect of theconcentration of EC (X2) was also in minus sign but itwas lesser than X1.c) Evaluation of tablet blendsEvaluation of prepared blend shows bulk density isbetween 0.39 to 0.47 gm/cm3, tapped density is 0.49to 0.59 gm/cm3, Carr’s Index is 16.07 to 23.72 % andAngle of Repose is 28.56 to 30.62 (F).d) Evaluation of tabletsEvaluation of prepared tablet shows hardness is 4.2 ±0.60 to 5.0 ± 0.55 kg/cm2, thickness is 2.84 ± 0.05 to2.98 ± 0.07 mm, friability is 0.30± 0.11 to 0.63± 0.19% and Weight variation is 100±1.15 to 100±3.50 mg.Batch F9 shows hardness is 4.7 ± 1.50 kg/cm2,



thickness is 2.92 ± 0.18 mm, friability is 0.30± 0.11 %and weight variation is 100±1.20 mg.e) In vitro dissolution studiesDissolution profiles of PDS sustained release matrixtablets of preliminary trials and factorial batches areshown in Figure 2, 3 & 4, respectively. From therelease profile we can see that batches F1 to F8shows release of drug in between 10.23-24.12 % at1st hour. Whereas, batch F9 shows that release ofdrug at 1st hours between 6 .12 %. Batches F1-F8shows that release of drug at 8th hour is between82.12 - 95.12 %. Whereas, batch F9 shows release ofdrug at 8th hour is 76.38 %.f) Accelerated stability study of best batch (F7)Sample withdraws at the interval of one month forthree months t showed no change in in-vitro drugrelease profile (Figure 5). Results of stability study donot show any remarkable change in the release profileof the PDS SR matrix tablet after the stability.g) Evaluation of Eudragit coated tableti) Physical EvaluationPhysical evaluation is based upon color, roughnessand uniformity of coating materials.ii) Disintegration study (Swelling study)Disintegration study was performed at various pHsolutions like 5.0, 6.0 and 7.0 in glass beaker andstudy was based on removing of coating layer. Ashown in Table 8, Coated tablet do not disintegrate inpH 5.0 and 6.0 where as in pH 7.0 breaking of layerstart progressively.iii) The in-vitro dissolution study of PDS SR matrixenteric coated tabletAs shown in Figure 6, Eudragit polymers are workseffectively for colon targeted delivery of prednisolonetablet. Both grades like Eudragit RS100 and EudragitFS30D are soluble at pH >7.0 or colonic pH. PEG-400is used as plasticizer with both coating agents.Eudragit RS100 will give drug release some fasterthan Eudragit FS30D in stimulated colonic fluid.Perfect drug release profiles was obtained by EudragitFS30D coating with PEG-400 as a plasticizer and pancoating will give sufficient coating efficiency withspraying method. Eudragit FS30D coatedprednisolone sustained release matrix tablet will doesnot give release in 0.1M HCL and 2% release in 4.5pH phosphate buffer and will dissolve uniformly at 7.2pH stimulated colonic fluid.

Conclusion(s)

In formulation PDS Sustained Release Matrix Tablet, a32 full factorial design was employed for preparation of

tablets possessing optimized characteristics (batchesF1 to F9). The amount of HPMC K-4M (X1) and EC (X2)were selected as independent variables. Cumulative% drug release selected as dependent variable(response; Y). Based on result of multiple linearregression analysis, it was concluded that dissolutionof tablet could be retarded for 8th hour when X2 is keptat high level. So role of polymer concentration is veryimportant in this formulation. From DSC study, we canshow that there is no change in drug’s melting peak(241.98°C) after the preparation of tablet. So we canconclude that drug and other excipients arecompatible which each other. While studying IRspectrum, we can conclude that there is no interactionbetween drug and other excipients. Stability study ofbatch F9 after three month showed no change inin-vitro drug release profile. It was concluded that byadopting a systematic formulation approach, anoptimum point could be reached in the shortest timewith minimum efforts.

References

1. Abdul B, John B. Perspective on colonic drugdelivery. Drug Delivery. 2003; 185.2. Chien Y. Novel drug delivery systems. 2nd Ed.;Marcel Dekker Inc: New York: 1992; 139-40.3. Gayton A, Hall J. Introduction and treatment tobowel diseases. 11th Ed. Textbook of medicalphysiology, 2006: 455.4. Rang HP and Dale MM. Drugs affectinggastrointestinal systems, 6th Ed; Churchill andlivingstone publisher, 2006; 342.5. Sarasija S and Hota A. Colon- specific drug deliverysystems. Ind. J. Pharm. Sci. 2002; 62(1): 1-8.6. www.wikipedia.com7. Ford J, Rubinstain MH, Hogan JE and Edgar AJ.Importance of drug type, tablet shape, added diluentson drug release from hydropropylmethylcellulosematrix tablets. Int. J. Pharm. 1987; 40: 223-234.8. Shah NH, Railkar AS, Phuapradit W, Zeng FW,Chen A, Infeld MH and Malick AW. Effect ofprocessing techniques in controlling the release rateand mechanical strengh of hydroxypropylmethylcellulose based hydrogel matrices. Eur. J.Pharm. Biopharm. 1996; 42:183-187.9. Reynolds TD, Gehrke SH, Hussain AS andShenoouda LS. Polymer erosion and drug releasecharacterization of hydroxypropyl methylcellulosematrices. J. Pharm. Sci. 1988; 87:1115-1123.10. Ceballos A, Cirri M, Maestrelli F, Corti G and MuraP. Influence of formulation and process variables on invitro release of theophylline from directly-compressed



Eudragit matrix tablets. IL Farmaco. 2005; 60: 913-918.11. Martin A. Micromeritics, In: Physical Pharmacy. 4thed. Philadelphia: Lippincott Williams & Wilkins; 2001;423-52.12. Banker GS, Anderson NR. Tablets. In: Lachman L,Lieberman HA, Kanig JL. The Theory and Practice ofIndustrial Pharmacy. 3rd ed. Philadelphia: PA: Lea &Febiger; 1986; 293-345.13. Gupta V, Beckert T, Deusch N and Hariharan M.Investigation of Potential Ionic Interactions BetweenAnionic and Cationic Polymethacrylates of MultipleCoatings of Novel Colonic Delivery System; Drug Dev.and Ind. Pharm. 2002; 28(2): 207–215.14. Khan M, Prebeg Z and Kurjakovic N. ApH-dependent colon targeted oral drug deliverysystem using methacrylic acid copolymers; Journal ofControlled Release 1999; 58: 215–222.



List of Figures:

Figure 1 (a) & (b): DSC spectras of PDS, HPMC K-100M, ethyl cellulose, starch, pectin

and their physical mixtures

Illustrations

Illustration 1

List of Figures and Tables



Figure 2: In vitro dissolution profiles release of batches P1 to P7



Figure 3: In-vitro dissolution profiles release of batches P8 to P10

Figure 4: In vitro dissolution profiles release of batches F1 to F9



Figure 5: Drug release profile of PDS SR matrix tablet before and after stability study of best batch F9



Figure 6: In vitro dissolution profiles release of batches FC1 to FC2



List of Tables:

Table 1. Formulation of preliminary trial

Ingredients Batch Code

P1 P2 P3 P4 P5 P6 P7 P8 P9 P10

PDS 5 5 5 5 5 5 5 5 5 5

HPMC K-4M - - - - - 5 10 10 10 10

HPMC K-100M 5 10 10 10 10 10 10 10 10 10

EC - - 3 5 8 5 5 5 5 5

Starch(binder) 7.5 7.5 7.5 7.5 7.5 7.5 7.5 7.5 7.5 7.5

Pectin - - - - - - - 10 20 30

Starch(Diluent) 78.5 73.5 70.5 68.5 65.5 63.5 58.5 48.

5

3 8 .

5

28.5

Talc 1 1 1 1 1 1 1 1 1 1

Mg Stearate 2 2 2 2 2 2 2 2 2 2

Aerosil 1 1 1 1 1 1 1 1 1 1

Total Wt. 100 100 100 100 100 100 100 100 100 100



Table 2: Physical characteristics of prepared blend of PDS

Batch

Code

Bulk density (gm/cc)

Tap density (gm/cc)

Carr’s index (%)

Angle of repose ()

P1

0.39

0.43

23.87

34.50

P2

0.41

0.51

21.21

30.57

P3

0.40

0.49

21.11

32.37

P4

0.34

0.55

19.92

41.62



P5

0.40

0.51

24.56

29.77

P6

0.40

0.55

21.63

31.58

P7

0.38

0.47

19.72

30.00

P8

0.35

0.46

20.45

29.15

P9

0.39

0.49

21.54

30.25

P10

0.41

0.39

23.45



32.54



Table 3: Evaluation parameters of PDS SR matrix tablet

Batch code Hardness(n=5) kg/cm2

Thickness(n=5) mm

%Friability(n=10)

W e i g h tVariation (n=20)

P1 4.2 0.30 2.80 0.13 0.33 0.33 100±2.50

P2 4.8 0.34 2.91 0.36 0.52 0.43 100±2.00

P3 4.6 0.10 2.93 0.46 0.39 0.67 100±2.74

P4 3.8 0.39 2.87 0.29 0.21 0.29 100±2.15

P5 4.7 0.78 2.92 0.49 0.13 0.19 100±2.54

P6 5.8 1.02 2.94 0.38 0.31 0.49 100±2.15

P7 4.5 0.37 2.96 0.48 0.30 0.81 100±2.54

P8 4.5 0.67 2.95 0.10 0.25 0.47 100±2.00

P9 4.7 0.45 2.95 0.12 0.28 0.27 100±2.54

P10 3.8 0.28 2.96 0.57 0.4 0.50 100±2.54



Table 4: Effect on dependent variable 32 full factorial design layouts for Sustained release

tablet of PRD

B a t c h

No

Variables levels in coded form

X1 X2

% Drug release (Q1) % Drug release (Q8)

F1 -1 -1 24.12 95.12

F2 -1 0 23.62 96.32

F3 -1 +1 21.28 91.13

F4 0 -1 18.12 94.72

F5 0 0 13.10 97.23

F6 0 +1 10.23 83.12

F7 +1 -1 11.12 93.16

F8 +1 0 10.34 90.30

F9 +1 +1 6.12 76.38

Translation of coded levels in actual units

Variables level Low (-1) Medium (0) High

(+1)

Concentration of HPMC K-4 M (X1) 5.0 % 10.0 % 15.0 %

Concentration of EC (X2) 3.0 % 5.0 % 8.0 %

Note: All the batches contained the constant amount of drug as 100 mg, rest process

parameters were kept constant and optimum.



Table 5: Summary of results of regression analysis for Sustained release matrix tablet

matrix of PDS

Coefficient B0 B1 B2 B11 B22 B12 Multiple R2

Q1 18.45 -6.447 -1.281 0.537 -0.123 0.949 0.9965

Q8 68.98 -10.21 -5.67 0.0145 2.389 1.167 0.987



Table 6: Physical characteristics of prepared blend of PDS

Batch

Code

Bulk density (gm/cc)

Tap density (gm/cc)

Carr’s index (%)

Angle of repose ()

F1

0.45

0.58

22.41

30.25

F2

0.40

0.52

23.07

28.79

F3

0.44

0.55

20.00

28.56

F4

0.41

0.53

21.15

29.00



F5

0.46

0.59

22.03

30.19

F6

0.47

0.56

16.07

29.67

F7

0.39

0.49

20.40

28.37

F8

0.45

0.59

23.72

30.62

F9

0.43

0.54

20.37

28.57



Table 7: Evaluation parameters of PDS SR matrix tablet

B a t c h

code

Hardness

kg/cm2 (n=10)

Thickness

mm(n=10)

%Friability

(n=10)

Weight Variation

(n=20)

F1 4.2 0.60 2.84 0.05 0.52 0.10 100±2.81

F2 4.6 1.00 2.87 0.12 0.46 0.11 100±2.65

F3 4.7 0.50 2.98 0.07 0.40 0.13 100±2.00

F4 4.9 1.20 2.95 0.17 0.63 0.19 100±3.50

F5 4.6 0.89 2.90 0.09 0.42 0.12 100±2.00

F6 5.0 0.55 2.87 0.04 0.28 0.14 100±2.74

F7 4.8 0.98 2.91 0.10 0.34 0.12 100±1.15

F8 4.3 1.20 2.88 0.15 0.37 0.17 100±2.54

F9 4.7 1.50 2.92 0.18 0.30 0.11 100±1.20



Table 8: Disintegration study of coated tablet

pH of solution Observations

5.0 Do not shows breaking of coating layer

6.0 Do not shows breaking of coating layer

7.0 Breaking of layer start progressively



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