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Chapter. 6 Results & Discussion

NIMS Institute Of Pharmacy, NIM S Un iversity Jaipur Page 65

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

6.2 Assay of API & Tablet

Figure 6.1Assay of standard API

Table 6.1 characterisation of API

DRUG API

1. Angle of repose (0) 22.222. Loose bulk density(g/ml) 0.353. Tapped bulk density(g/ml) 0.494. Carrs index (%) 39.455.Hausnrs ratio 1.40


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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 QUANTITY OF DRUG 300 300 300

2 LACTOSE MONOHYDRATE 177 177 169.5

3 HPMC K4M - - -

4 HPMC K15M 40 - -

5 HPMC K100M 40 50

6 IPA Q.S Q.S Q.S

7 MCC 59 59 56.5

8 COLLOIDAL SILICONE

DIOXIDE

6 6 6

9 TALC 12 12 12

10 MG STEARATE 6 6 6

11 TOTAL 600 600 600


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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 indexand Hausners ratio

Result of Angle of Repose And Compressibility index of batch no f001 to foo3The 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 (


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6.3.2 Evaluation of tablet:

The formulations were evaluated for different parameter like hardness, friability, and 5.41-

5.42

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: 0.1N HCL/ PH6.8Phosphet Buffer

Temperature: 37+ 2C

Volume of Medium: 900ml

Sample Drawn: 10 ml

Apparatus: Basket

R.P.M.: 100

Dilution: 5ml in 100ml

.

Table 6.2.2Result of evaluation of tablets of trial batches F001 to F003

Trial

batch

es

Hardne

ss (kP)ckness

mm)

Friabilit

y (%)

Avg.

Wt.

(mg)

Assay (%)

F001 16-17 5.41-5.42 Nil 600 98.80

F002 16-17 5.41-5.42 Nil 600 97.5

F003 16-17 5.41-5.42 Nil 600 97.6


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Figure 6.3 Dissolution data of drug release

0

20

40

60

80

100

120

0 1 2 4 8 12

%drugrelease

f1

f2

f3

Table 6.2.3 Drug release profile of trail F/001 to F/003

Time

(hrs) F/001 F/002 F/003

0.1N HCL

1 62.2 40.8 45.4

2 85.8 64.2 63.8

PH6.8Phosphet Buffer

4 98.7 87.6 79.8

8 97.2 97 98.4

12 95.1 96.9 96.5


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6.4 Evaluation Formulation of trials F004 TO F008:-

Table6.3 Formulation of trialsF004 TO F008

Sr

n

o

INGREDIENT F/004 F/005 F/006 F/007

1 QUANTITY OF DRUG 300 300 300 300

2 LACTOSE

MONOHYDRATE

162 162 162 162

3 HPMC K4M - 10 20 30

4 HPMC K15M - - - -

5 HPMC K100M 60 50 40 30

5 IPA Q.S Q.S Q.S Q.S

6 MCC(MICROCRYSTEL

LAIYINE CELLULOSE)

54 54 54 54

7 COLLOIDAL SILICONE

DIOXIDE

6 6 6 6

8 TALC 12 12 12 12

9 MGNESIUM

STEARATE

6 6 6 6

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:

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 (


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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 5.41-

5.42

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: 0.1N HCL/ PH6.8Phosphet Buffer

Temperature: 37+ 2C

Volume of Medium: 900ml

Sample Drawn: 10 ml

Apparatus: Basket

R.P.M.: 100

Dilution: 5ml in 100ml

Table 6.3.2 Result of evaluation of tablets of trial batches F004 to F007

Trial

batches

Hardne

ss (kP)

Thickne

ss

(mm)

Friabi

lity

(%)

Avg.

Wt.

(mg)

Assay (%)

F004 16-17 5.41-5.42 Nil 600 98.7

F005 16-17 5.41-5.42 Nil 600 97.8

F006 16-17 5.41-5.42 Nil 600 98.4

F007 16-17 5.41-5.42 Nil 600 94.3


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Figure 6.4 Dissolution data of drug release

0

20

40

60

80

100

120

0 1 2 4 8 12

%

d

r

u

g

r

e

l

e

a

s

e

time(hr)

drug release

f4

f5

f6

f7

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 49.4 36.6 25.9 23.9

2 45.8 44.2 39.1 35.9

PH6.8

4 69.9 64.2 58.9 53.4

8 99 95.7 92.1 89.7

12 98.3 103.2 104.5 97.4


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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 monthsTable 6.6.1Evaluation parameters of stability batch after 1 months

Formulation

Code

Parameters Storage time

0 month 1 month

Drug content,

%101.34 100.24

Physical

appearance

No discolor-

ation

No discolor-ation


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Comparison of dissolution of optimized tablet (F07) of initial and after 1 months stability studyTable 6.6.2Comparison of dissolution of optimized tablet (F07) of initial and after 1 months

Time(min) Initial After 1months

1 23.9 23..3

2 35.9 32.2

4 53.4 50.0

8 89.7 85.01

12 97.4 95

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

0

20

40

60

80

100

120

0 1 2 4 8 12

%D

rugrelease

time(min)

dissolution profile

Initial

After 1 Months

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