DEPARTEMENT OF PHARMACEUTICS

CHAPTER VI

RESULTS AND DISCUSSION

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Table 6.1: Solubility Studies of ABZ in Different Dissolution Media

S.NO DISSOLUTION MEDIA AMOUNT OF DRUG

SOLUBULE(mg/ml)

1 PURIFIED WATER 0.13

2 INTESTINAL FLUID 0.21

3 PUREIFIED WATER(@209ºC)
0.75

ANALYTICAL METHOD:

1.Albendazole stock solution preparation:

2.Standard solution was prepared by dissolving 100mg of albendazole in

100ml Glacial.Acetic.Acid(G.A.A(methanolic))

METHOD DEVELOPMENT:

Aliquots of stock solution were further diluted with

(methanolic)glaceial.acetic.acid to get working solution of
5,10,15,20,25,30ug/ml and the working standards were scanned between
200-400nm which shows the maximum absorbance at 299nm

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Spectrum Scan:1

Table 6. 1: Calibration curve for the estimation of ABZ in ACETIC ACID BUFFER.

S.NO CONCNETRATION(µg/ml) ABSORBANCE

1 5 0.244

2 10 0.31

3 15 0.511

4 20 0.67

5 25 0.84

6 30 1.02

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1.2 Graph1:

0.8
ABSORBANCE (299nm)

0.6

Linear ()

0.4

0.2

0
0 1 2 3 4 5 6 7 8 9
CONCENTRATION ug/ml

Calibration curve for the estimation of ABZ in ACETIC ACID BUFFER

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6.2 INGRIDIENTS/COMPOSITION
MANNITOL PVP K30
ABZ
[ SOLID
DISPERSION]
1:1 1:2 1:3 1:1 1:2 1:3

SOLID 400 600 800 400 600 800

DISPERSION
[MIX]

CROSPOVIDNE 9 18 27 36 45 54

LACTOSE 473 264 55 346 237 28

MONOHYDRATE

AEROSIL 9 9 9 9 9 9

MAGNESIUM
STERATE 9 9 9 9 9 9

WEIGHT PER
TABLET 900 900 900 900 900 900

6.3 PREFORMULATION STUDIES ON ABZ SOLID DISPERSION’S

METHOD EVALUATED
S.NO DESCRIPTION
PHYSICAL ASSAY
0 DAY 1 MONTH 0 DAY 1 MONTH
1 ABZ:M(1:1) WHITE COMPLIED COMPLIED COMPLIED
2 ABZ:M(1:2) WHITE COMPLIED COMPLIED COMPLIED
3 ABZ:M(1:3) WHITE COMPLIED COMPLIED COMPLIED
4 ABZ:PVP WHITE COMPLIED COMPLIED COMPLIED
K30(1:1)

5 ABZ: PVP WHITE COMPLIED COMPLIED COMPLIED

K30(1:2)

6 ABZ:PVP WHITE COMPLIED COMPLIED COMPLIED

K30(1:3)

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6.4 TABLE

S.NO SOLID ANGLE OF CARR’S DRUG

DISPERSION REPOSE INDEX
CONTENT
(%)

1 ABZ:M(1:1) 20.92+0.47 14.75 95.13

2 ABZ:M(1:2) 26.28+1.63 15 96.16

3 ABZ:M(1:3) 22.77+0.43 12.06 95.14

4 ABZ:PVP 23.48+0.66 10.71 96.45

K30(1:1)

5 ABZ:PVP 25.86+0.44 8.71 97.46

K30(1:2)

6 ABZ:PVP 23.21+0.4 13.33 97.78

K30(1:3)

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Spectrum Scan:2 FTIR OF ALBENDAZOLE PURE DRUG

Spectrum Scan:3 FTIR REPORT PVP K-30

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Spectrum Scan:4 ABZ:PVP K30 1:3 SOLID DISPERSIONS FTIR REPORT

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6.5 TABLE

IR Spectra Peak of functional groups[Wavelength(cm-1)]

FUNCTIONAL GROUP
C-H N-H C-N C=O group

Stretch Bending Vibration

Reference standard 2962-2853 1640-1550 1220-1020 1750-1730

Albendazole+PVP K-30 2956 1587 1224 1629

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6.6 COMPOSITION OF VARIOUS SOLID DISPERSIONS OF ABZ

S.NO COMPOSITION RATIO AMOUNT OF

DRUG
SOLUBULE
(mg/ml)

1 ABZ:MANNITOL 1:1 0.5

2 ABZ:MANNITOL 1:2 1.1

3 ABZ:MANNITOL 1:3 1.04

4 ABZ:PVP K30 1:1 1.19

5 ABZ:PVP K30 1:2 1.97

6 ABZ:PVP K30 1:3 2.09

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6.7 Table : In- vitro drug release profile

S. %CUMULATIVE DRUG RELEASE

NO ABZ:M ABZ:M ABZ:M ABZ:PVP ABZ:PVP ABZ:PVP
TIME (1:1) (1:2) (1:3) K30 K30 K30
(MIN) (1:1) (1:2) (1:3)

1 0 0 0 0 0 0 0

2 5 14 13.44 12.8 11.30 11.05 15.07

3 10 18.22 17 15 14.6 28.30 34.36

4 20 28.90 22.12 24.08 25.28 49.13 72.09

5 30 39.1 35.18 32 43.25 76.26 90.29

6 40 62.5 59.5 56 51.7 94.8 96.69

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120

100

80
%DRUG RELEASE

ABZ:MANNITOL 1:1
60 ABZ:MANNITOL 1:2
ABZ:MANNITOL 1:3
ABZ:PVP K30 1:1
40 ABZ:PVPK30 1:2
ABZ: PVP K30 1:3

20

0
0 5 10 15 20 25 30 35 40 45
TIME IN MIN

Graph:2DISSOLUTION PROFILE OF SOLID DISPERSIONS OF ALBENDAZOLE

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120

100

%DRUG RELEASE 80
ABZ:MANNITOL 1:1
ABZ:MANNITOL 1:2
60
ABZ:MANNITOL 1:3
ABZ:PVP K30 1:1
40
ABZ:PVP K30 1:2
ABZ:PVP K30 1:3
20 PURE ABZ

0
0 5 10 15 20 25 30 35 40 45
TIME IN MIN

Graph:3 DISSOLUTION PROFILE OF SOLID DISPERSIONS OF ALBENDAZOLE

WITH PURE DRUG

70

60

50

40
ABZ:MANNITOL 1:3
ABA:MANNITOL 1:1
30 ABZ:MANNITOL 1:2

20

10

0
0 5 10 15 20 25 30 35 40 45

Graph:4DISSOLUTION PROFILE OF ABZ:MANNITOL SOLID DISPERSION BY

SOLVENT EVAPOURATION METHOD

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120

100

80
%DRUG RELEASE

60 ABZ:PVP K30
1:1

ABZ:PVP K30
1:2
40
ABZ:PVP K30
1:3

20

0
0 10 20 30 40 50 60
TIME IN MINS

Graph:5 5 ZERO ORDER GRAPH: DISSOLUTION PROFILE OF ABZ:PVPK30

SOLID DISPERSION BY SOLVENT EVAPOURATION METHOD

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GRAPH: 6 FIRST ORDER PLOT OF ABZ:MANNITOL SOLID DISPERSION

PREPARED BY SOLVENT EVAPOURATION METHOD

2.5

2
LOG%DRUG REMAINING

1.5
ABZ:MANNITOL 1:1
Linear (ABZ:MANNITOL 1:1)
ABZ:MANNITOL 1:2
1 Linear (ABZ:MANNITOL 1:2)
ABZ:MANNITOL 1:3
Linear (ABZ:MANNITOL 1:3)

0.5

0
0 20 40 60 80 100 120

TIME IN MIN

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GRAPH:7 FIRST ORDER PLOT OF ABZ:PVP K30 SOLID DISPERSION

PREPARED BY SOLVENT EVAPOURATION METHOD

2.5

2
LOG%DRUG DISSOLVED

1.5
ABZ:PVP K30 (1:1)
Linear (ABZ:PVP K30 (1:1))
ABZ:PVP K30 (1:2)
1 Linear (ABZ:PVP K30 (1:2))
ABZ:PVP K30 (1:3)
Linear (ABZ:PVP K30 (1:3))

0.5

0
0 10 20 30 40 50 60
TIME IN MIN

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6.8TABLE: Release exponent and rate constant values for all solid
dispersion formulations

KINETICS
S.NO FORMULATION ZERO FIRST ORDER
S ORDER R2
R2

1 ABZ:MANNITOL 0.977 0.973

(1:1)
ABZ:MANNITOL
2 (1:2) 0.957 0.968

ABZ:MANNITOL
3 (1:3) 0.949 0.867

ABZ:PVP K30
4 (1:1) 0.985 0.978

ABZ:PVP K30
5 (1:2) 0.996 0.985

ABZ:PVP K30
6 (1:3) 0.943 0.982

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6.9 Dissolution parameters of Solid dispersions

S.NO PARAMETERS ABZ:M ABZ:M ABZ:M ABZ:PVP ABZ:PVP ABZ:PVP

(1:1) (1:2) (1:3) K30 K30 K30
(1:1) (1:2) (1:3)

1 PD10 18.22 17 15 14.60 28.30 34.36

2 T1/2 29.38 24.38 35.48 38.52 10.53 8.07

3
DE30(%) 21.91 19.57 14.44 20.04 35.35 43.35

4 K1*102 2.35 2.842 1.95 1.7 6.58 8.58

5 T50 36.4 38.2 34.5 39.7 20.5 18.9

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PREFORMULATION STUDIES ON FORMULATIONS F1-F6

6.9.1Table :Angle of Repose, Loose Bulk Density, Tapped Bulk Density and Carr's
Compressibility Index, Hausner’s ratio:
Formul ANGLE OF BULK TAPPEDDEN %COMPR HAUSSNERS
ations REPOSE DENSITY SITY ESSIBILI RATIO
TY

F1 30.96±99 0.400±0.006 0.466±0.007 13±0.47 1.15±0.015

F2 34.50±1.01 0.411±0.005 0.482±0.007 14.58±1.3 1.17±0.005

9

F3 34.21±1.04 0.378±0.004 0.411±0.008 9.75±0.18 1.10±0.009

F4 33.02±0.92 0.358±0.003 0.424±0.003 15.06±1.3 1.18±0.019

F5 31.79±0.20 0.341±0.001 0.424±0.003 14.04±1.0 1.16±0.004

5

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6.9.2CHARECTRIZATION OF TABLETS

FORMULATION HARDNESS FRIABILITY DISINTEGRATIO DRUG

N CONTENET%

F1 3.20±0.10 0.28 11.12 99

F2 3.27±0.025 0,95 9.23 99.85

0.88
F3 3.30±0.08 8.05 99.75

F4 2.50±0.03 0.97 5.6 99.95

F5 2.65±0.05 0.48 4 99.8

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6.9.3 Table : In- vitro drug release profile

S TIME %DRUG RELEASE

. IN
N MINS F1 F2 F3 F4 F5 F6
O
1 0 0 0 0 0 0 0

2 5 58.54 59.85 61.13 59.85 62.91 69.98

3 10 61.13 66.46 63.69 64.48 66.46 68.06

4 20 64.73 74.25 76.54 74.25 75.26 82.98

5 30 73.26 82.98 85.34 82.48 85.95 89.93

6 40 86.85 89.12 89.38 91.58 96.61 97.06

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F1-F6 COMPARED TO PURE DRUG

120

100

80
F1
F2
%DRUG RELEASE

F3
60 F4
F5
F6

40

20

0
0 5 10 15 20 25 30 35 40 45
TIME IN MIN

Graph:8DISSOLUTION PROFILE OF ABZ TABLET FORMULATIONS F1-F6

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120

100

80
% DRUG RELEASE

F
1
60 F
2
F
3
40 F
4
F
5
20

0
0 5 10 15 20 25 30 35 40 45

TIME IN MIN

Graph:9 ZERO ORDER GRAPH

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2.5

F1
LOG%DRUG REMAINING

Linear (F1)
1.5 F2
Linear (F2)
F3
Linear (F3)
1 F4
Linear (F4)
F5
Linear (F5)
F6
0.5 Linear (F6)

0
0 1 2 3 4 5 6 7 8
TIME IN MINS

Graph:10 ABZ F1-F6 FORMULATIONS FISRT ORDER GRAPH

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COMPARITIVE GRAPH OF F6 FORMULATION WITH PURE DRUG ABZ

120

100

80
%DRUG RELEASE

60 F6
PURE DRUG ABZ

40

20

0
0 5 10 15 20 25 30 35 40 45

TIME IN MIN

Graph:11COMPARATIVE DISSOLUTION GRAPH OF PURE ABZ WITH F6

FORMULATION

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6.9.4 TABLE: Release exponent and rate constant values for all
prepared formulations(F1-F6)

S.NO FORMULATIONS KINETICS

ZERO ORDER FIRST ORDER
R2 R2

1 F1 0.637 0.8478

2 F2 0.6973 0.8987

3 F3 0.6473 0.911

4 F4 0.66 0.8252

5 F5 0.63 0.9029

6 F6 0.6553 0.9514

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6.9.5TABLE

S.NO PARAMETERS F1 F2 F3 F4 F5 F6

1 PD10 38.87 33.54 36.31 35.02 33 31.94

2 T50 4.5 4.85 4.95 4.634 3.56 3.98

3
DE30(%) 50.18 54.69 55.2 54 56.39 59.08

4 T1/2 16.63 14.74 14.08 13.86 13.6 9.84

5 K1*102 4.167 4.71 4.928 5.06 5.07 7.04

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6.9.6 Result of the stability studies of optimized F6 formulation

Evaluation parameters

Time Colour Hardness Drug % CDR Disintegration

(kg/cm2) content time (sec.)
Uniformity
(mg)
Day 0 White 2.67+0.05 883+1.01 97.1+1.01 45+1.5

After 1 White 2.65±0.05 873+1.01 97.00±1.01 45±1.5

month

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RESULT

All the solid dispersions prepared were found to be fine and free flowing powders. In the

percent drug content values indicated that the drug content was uniform . The drug release

profile was studied in 0.1 N Hcl containing was added to the dissolution medium to maintain

sink condition during dissolution rate study. The dissolution profiles of

Various ratios of sold dispersions were shown in gaph:2 .

It is clear that the dissolution of ABZ has enhanced considerably from PVP k30 1:3 solid

dispersions compared to dissolution of plain drug.

The reason for the poor dissolution of pure drug could be poor wettability and agglomeration

of particles. And it can be seen that the dissolution of ABZ increases with increase in PVP

K30 to 1:3 ratio of drug: PVP k30.

This might be due to complete dispersion of drug with PVP k30 at 1:3 ratio. . The dissolution

of ABZ as such and prepared solid dispersions followed First order kinetics. The dissolution

rate constants (k1) were calculated from the slopes of the first order linear plots of the

dissolution data. Dissolution efficiency (DE30) values based on the dissolution data were

calculated according to

Khan (Khan et al., 1975). T50 (Time taken for 50% dissolution) values were recorded from

the dissolution profiles

All the solid dispersions prepared were evaluated for Carr’s index, and drug content. It was

found that all the dispersions exhibited excellent flow properties and fair compressibility

index. . The drug content for all dispersions were in the range of 95– 97.78 %. Thus all the

solid dispersions are suitable for compression as Fast dissolving tablets(6.2 table).

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Dissolution studies were performed for all the solid dispersions by using USP apparatus II

(paddle). The drug from various dispersions were released at a faster rate . The drug release

from solid dispersions were in the order of ascending i.e., PVP K30 1:3>PVP K30 1:2> PVP

K30 1:1 >MANNITOL 1:3> MANNITOL 1:2> MANNITOL1:1 and Solid dispersion of

PVP k30 1:1 R2 was found to be 0.98 (from table 6.8)

The Pre-formulation studies of Albendazole were performed ,the FT-IR analysis revealed that

the polymers and drug were compatible.

All the formulations showed rapid % drug release (86.85% - 97.06%). Formulations F1, F2,

F3, F4 and F5, and F6 showed 86.85%, 89.21%, 89.93%, 91.98%, , 96.61%, 97.06%(6.9.3

table)

Among All the prepared batches of tablets the Formulation F-6 has optimized formulation

and showed the maximum release of (97.06%) at the end of 40 mins. And R2 Value was

found to be 0.95(6.9.4 table).

The super dis-integrant crospovidone of incorporated 6% showed the better drug release and

dissolution rate among the one incorporated with 1 to 5%( table 6.2)

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STABILITY STUDIES
Stability studies for the developed formulations were carried out by storing
the selected formulations 40+0.5ºC 75% RH for one month. The formulation
F6 was selected on the basis of their high cumulative percentage drug
release, and also results of in-vitro disintegration time, wetting time. After
one month, the tablets were analyzed for the colour, hardness, drug content
uniformity and cumulative % drug
released, in-vitro disintegration time. These formulations showed no
significant changes in the values which was showed in table 6.9.6

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