Chapter.

Results & Discussion

6. RESULTS & DISCUSSION

6.1 Result of Characterisation of API: The powder of API was evaluated for Angle of repose, Bulk density, Tapped density, Carrs index and Hausners ratio.API were evaluated and its result shown in Table 6.1

Table 6.1 characterisation of API DRUG

1. Angle of repose (0 )

API 22.22 0.35 0.49 39.45 1.40

2. Loose bulk density(g/ml) 3. Tapped bulk density(g/ml) 4. Carrs index (%) 5.Hausnrs ratio 6.2 Assay of API & Tablet

Figure 6.1Assay of standard API

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Figure 6.2Assay of tablet:

Figure 6.1 & 6.2:- Assay result of API& Tablet was given in

First prepare buffer solution by 2.7gm KHPO4in 2 litre purified water. Then prepare mobile phase by addition of ACN with the ratio of 40:60.Then prepare diluent with addition of water: methanol (40:60). Finally 50 mg API is added in to the 25 ml diluent. The max of API in the above media was determined by scanning a suitable dilution of the stock. From the stock solution, various dilutions were made to obtain solutions of 1, 5, 10, 15 and 20 _g/ml, and absorbance was measured for each dilution.

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6.3 Result of Evaluation of Formulation of F001 to F003:-

6.2 FORMULATION OF TRIALS F001 TO F003

SR NO

INGREDIENT

F-1

F-2

F-3

1 2

QUANTITY OF DRUG LACTOSE MONOHYDRATE

300 177

300 177

300 169.5

3 4 5 6 7 8

HPMC K4M HPMC K15M HPMC K100M IPA MCC COLLOIDAL SILICONE DIOXIDE

40

40

50 Q.S 56.5 6

Q.S 59 6

Q.S 59 6

9 10 11

TALC MG STEARATE TOTAL

12 6 600

12 6 600

12 6 600

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6.3.1 Evaluation of powder blends of F001 to F003: The powder blend of trail batches of API were evaluated for Angle of repose, Bulk density, Tapped density, Carrs index and Hausners ratio Table 6.2.1 Result of evaluation of powder blend of trial batches F001 to F003

Trails Angle of repose () Bulk density(g/ml) Tapped density(g/ml) Carrs index(%) Hausners ratio

F/OO1 24.69

F/002 23.31

F/003 24.31

0.462

0.438

0.431

0.524

0.517

0.504

11.83

15.28

14.48

1.13

1.18

1.17

Result of Angle of Repose And Compressibility index of batch no f001 to foo3 The results of angle of repose and compressibility index ranged from 23.31 to 25.14 and 11.83 to 15.28 respectively. The results of Hausners ratio ranged from1.13 to 1.18. The results of angle of repose (<30) indicate good flow properties of the powder. This was further supported by lower compressibility index values. Generally, compressibility index values up to 15% results in good to excellent flow properties

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6.3.2 Evaluation of tablet: The formulations were evaluated for different parameter like hardness, friability, and 5.415.42 Table 6.2.2Result of evaluation of tablets of trial batches F001 to F003 Trial batch es F001 F002 F003 16-17 16-17 16-17 Hardne ss (kP) (mm) 5.41-5.42 5.41-5.42 5.41-5.42 Nil Nil Nil Thickness Friabilit y (%) Avg. Wt. (mg) 600 600 600 98.80 97.5 97.6 Assay (%)

Hardness of the prepared tablets was found in range of 16-17kp for 300mg . All the tablet formulations showed acceptable pharmacotechnical properties and complied with the in-house specifications for weight variation, drug content, hardness, and friability 6.3.3Drug release profile of trail F/001 to F/003:Dissolution Parameter : Dissolution Media: Temperature: Volume of Medium: Sample Drawn: Apparatus: R.P.M.: Dilution: . 0.1N HCL/ PH6.8Phosphet Buffer 37+ 2C 900ml 10 ml Basket 100 5ml in 100ml

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Table 6.2.3 Drug release profile of trail F/001 to F/003 Time (hrs) F/001 F/002 0.1N HCL 1 2 62.2 85.8 40.8 64.2 PH6.8Phosphet Buffer 4 8 12 98.7 97.2 95.1 87.6 97 96.9 79.8 98.4 96.5 45.4 63.8 F/003

120 100

%drug release

80 f1 60 40 20 0 0 1 2 4 8 12 f2 f3

Figure 6.3 Dissolution data of drug release

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6.4 Evaluation Formulation of trials F004 TO F008:-

Table6.3 Formulation of trialsF004 TO F008

Sr n o 1 2

INGREDIENT

F/004

F/005

F/006

F/007

QUANTITY OF DRUG LACTOSE MONOHYDRATE

300 162

300 162

300 162

300 162

3 4 5 5 6

HPMC K4M HPMC K15M HPMC K100M IPA MCC(MICROCRYSTEL LAIYINE CELLULOSE)

60 Q.S 54

10 50 Q.S 54

20 40 Q.S 54

30 30 Q.S 54

7 8 9

COLLOIDAL SILICONE DIOXIDE

6 12 6

6 12 6

6 12 6

6 12 6

TALC MGNESIUM STEARATE

10

TOTAL

600

600

600

600

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6.4.1 (D) Result and Discussion of Batch no.F004toF007:6.4.1 (D).1 Evaluation of powder blend: Table 6.3.1 Result of evaluation of powder blend of trial batches F004 to F007

Trails

F/OO4

F/005

F/006

F/007

Angle of repose () Bulk density(g/ml) Tapped density(g/ml) Carrs index(%) Hausners ratio

25.14 0.459

23.31 0.459

24.31 0.456

24.31 0.456

0.534

0.534

0.529

0.529

14.04

14.48

15.28

14.48

1.16

1.18

1.18

1.17

The powder blend of trail batches of API were evaluated for Angle of repose, Bulk Density, Tapped density, Carrs index and Hausners ratio. The results of angle of repose and compressibility index ranged from 23.31 to 25.14 and 11.83 to 15.28 respectively. The results of Hausners ratio ranged from1.13 to 1.18. The results of angle of repose (<30) indicate good flow properties of the powder. This was further supported by lower compressibility index values. Generally, compressibility index values up to 15% results in good to excellent flow properties

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6.4.1 (D).2 Evaluation of tablet Batch no F004 to F007 The formulations were evaluated for different parameter like hardness, friability, and 5.415.42 Table 6.3.2 Result of evaluation of tablets of trial batches F004 to F007 Hardne Trial batches (mm) F004 F005 F006 F007 16-17 16-17 16-17 16-17 5.41-5.42 5.41-5.42 5.41-5.42 5.41-5.42 ss (kP) Thickne ss Friabi lity (%) Nil Nil Nil Nil Avg. Wt. (mg) 600 600 600 600 98.7 97.8 98.4 94.3 Assay (%)

Hardness of the prepared tablets was found in range of 16-17kp for 300mg. All the tablet formulations showed acceptable pharmacotechnical properties and complied with the in-house specifications for weight variation, drug content, hardness, and friability.

6.3.3Drug release profile of trail F/004 to F/007:Dissolution Parameter : Dissolution Media: Temperature: Volume of Medium: Sample Drawn: Apparatus: R.P.M.: Dilution: 0.1N HCL/ PH6.8Phosphet Buffer 37+ 2C 900ml 10 ml Basket 100 5ml in 100ml Page 73

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Table 6.3.3 Result of dissolution of trail F004 to F007 Time (hrs) F/004 F/005 F/006 F007

0.1N HCL 1 2 49.4 45.8 36.6 44.2 PH6.8 4 8 12 69.9 99 98.3 64.2 95.7 103.2 58.9 92.1 104.5 53.4 89.7 97.4 25.9 39.1 23.9 35.9

120 100 % d r u g r e l e a s e 80 60 40 20 0 0 1

drug release

f4 f5 f6 f7

2 time(hr)

12

Figure 6.4 Dissolution data of drug release

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6.4.1 (D).3 In-vitro dissolution Study: The result of In-vitro dissolution study of trail batches F/001 to F/007 are shown in the following table: The results of In-Vitro dissolution study of trial F/001 which was taken by the HPMC K 15M were shown fast drug release. Formulation F001 was failed to generate Extended release of drug up to 4hr and drug was completely release at 8hrs .So we took next trial with HPMC K100M of about 4 % . But release of drug from the tablet was faster than the Sustained release. It showed much higher release in the 0.1 N HCl so conclude that HPMC K100M was not given extended release effect in the body. Trial F/003 was taken by HPMC K100M as granulating agent but the result was not good. Drug was released faster in the 0.1 N HCl whereas it showed slow release in the 6.8 Phosphate buffer .so dropped this trail and came to granulation with HPMC K100M +HPMC K4M. Trial F/005 was taken by HPMC K100

M+HPMC K4M as granulating Viscosity Enhancer &matrix forming polymer. Drug release was slow as compared to targeted drug in both 0.1 N HCl and 6.8 Phosphate buffer and so decided that HPMC K100 M+HPMC K4M was very low permeable to drug as coating material. Trial F/006drug release was slow as compared to targeted drug in both medium. In trial F/007 we decided that HPMC K100M +HPMC K4M (30+30%) was slow as compared to targeted drug in both 0.1 N HCl and 6.8 Phosphate buffer. 6.4 (D).4 Selection of packaging material: Tablets will be packed in a blister formed by the following primary packaging components. Base foil: PVC/PVDC blister pack. Lidding Material: 0.025 mm aluminum foil
Justification: PVC/PVDC Blister pack provides complete protection against light, water vapour, gases etc.

6.5Conclusion From the result, concluded that batch taken in combination with HPMC K4M&HPMC K100M (30+30%) in has good sustained property. Batch F007 was charged for Accelerated stability study.

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6.6. Stability studies of optimized tablets The ICH Guidelines have established that long term stability testing should be done at 25C2C / 60%5% RH; stress testing should be done at 40C2C / 75%5% RH for 6 months. If significant change occurs at these stress conditions, then the formulation should be tested at an intermediate condition at 30C2C /75%5% RH. Table 6.7 shows different temperatures and period of stability testing. The stability studies of the optimized tablets were carried out at 40C temperature and 75 % relative humidity (accelerated stability) in stability chamber for three months. Tablets were withdrawn at 1, 2, 3 months intervals and evaluated for disintegration time, hardness, drug content and in vitro release.

Evaluation parameters of stability batch after 1 months Table 6.6.1Evaluation parameters of stability batch after 1 months Parameters 0 month Formulation Code Drug content, % Storage time 1 month

101.34

100.24

Physical appearance

No discoloration

No discolor-ation

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Comparison of dissolution of optimized tablet (F07) of initial and after 1 months stability study
Table 6.6.2Comparison of dissolution of optimized tablet (F07) of initial and after 1 months Time(min) 1 2 4 8 12 Initial After 1months 23..3 32.2 50.0 85.01 95

23.9 35.9 53.4 89.7 97.4

Figure 6.6 Comparison of dissolution of optimized tablet (F07) of initial and after 1 months

120 100

dissolution profile

% Drug release

80 60 40 20 0 0 1 2 time(min) 4 8 12 Initial After 1 Months

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