17
127 Chapter 7 Formulation, Evaluation of ASA-suppositories Suppositories loaded ASA-nanoparticles 7.0 Formulation and evaluation of ASA suppositories, Suppositories loaded ASA-nanoparticulates 7.1 Preparation of ASA-suppositories ASA containing glycerinated gelatin suppository formulations prepared based on fusion method. Variable concentrations of gelatin and glycerin were weighed accurately. The concentration of glycerin and gelatin were varied for each formulation to select the best optimized formulation 1 . Twenty four formulations were prepared (Fs1-Fs24) by fusion method. The amount of drug and base required was calculated based on the displacement. Glycerin, gelatin and water melted to 60 C, over water bath followed by the addition of micronized ASA under stirring to have content uniformity. The mixture was cooled to 50 C and poured in to the pre calibrated metallic mould and placed into the refrigerator for solidification shown in table 7.1. 7.2 Preparation of gelatin suppositories loaded ASA- nanoparticles ASA-nanoparticles loaded in to the suppositories as discussed in the literature. Glycerinated gelatin was selected as the base for loading nanoparticles. Based on literature drug diffusion efficiency was comparatively more in glycerinated gelatin. Based on the previously performed characterization studies for the nanoparticles and ASA suppositories, best formulations were selected, and based on displacement value 100 mg of ASA nanoparticles were added to the molten base and suppositories were prepared by fusion process in metallic mould 2 . The base which was fused at 60C, then

7.0 Formulation and evaluation of ASA suppositories ...shodhganga.inflibnet.ac.in/bitstream/10603/15801/13/13_chapter 7.pdf128 Chapter 7 Formulation, Evaluation of ASA-suppositories

Embed Size (px)

Citation preview

Page 1: 7.0 Formulation and evaluation of ASA suppositories ...shodhganga.inflibnet.ac.in/bitstream/10603/15801/13/13_chapter 7.pdf128 Chapter 7 Formulation, Evaluation of ASA-suppositories

127

Chapter 7 Formulation, Evaluation of ASA-suppositories

Suppositories loaded ASA-nanoparticles

7.0 Formulation and evaluation of ASA suppositories, Suppositories

loaded ASA-nanoparticulates

7.1 Preparation of ASA-suppositories

ASA containing glycerinated gelatin suppository formulations prepared based on

fusion method. Variable concentrations of gelatin and glycerin were weighed accurately.

The concentration of glycerin and gelatin were varied for each formulation to select the

best optimized formulation1.

Twenty four formulations were prepared (Fs1-Fs24) by fusion method. The

amount of drug and base required was calculated based on the displacement. Glycerin,

gelatin and water melted to 60 ⁰C, over water bath followed by the addition of

micronized ASA under stirring to have content uniformity. The mixture was cooled to

50 ⁰C and poured in to the pre calibrated metallic mould and placed into the refrigerator

for solidification shown in table 7.1.

7.2 Preparation of gelatin suppositories loaded ASA- nanoparticles

ASA-nanoparticles loaded in to the suppositories as discussed in the literature.

Glycerinated gelatin was selected as the base for loading nanoparticles. Based on

literature drug diffusion efficiency was comparatively more in glycerinated gelatin.

Based on the previously performed characterization studies for the nanoparticles and

ASA suppositories, best formulations were selected, and based on displacement value

100 mg of ASA nanoparticles were added to the molten base and suppositories were

prepared by fusion process in metallic mould2. The base which was fused at 60⁰C, then

Page 2: 7.0 Formulation and evaluation of ASA suppositories ...shodhganga.inflibnet.ac.in/bitstream/10603/15801/13/13_chapter 7.pdf128 Chapter 7 Formulation, Evaluation of ASA-suppositories

128

Chapter 7 Formulation, Evaluation of ASA-suppositories

Suppositories loaded ASA-nanoparticles

the nanoparticles was added and stirred with glass rod to have content uniformity and

poured in to the one gram metallic mould and solidified in refrigerator by keeping

overnight. Composition of suppositories loaded ASA- nanoparticles was shown in table

7.2.

Table 7.1 Representing different formulation and their composition of ASA-

suppositories

Formulation

code

Gelatin

(gm)

Glycerin(gm)

Water(gm)

ASA(mg)

FS1 0.663

5.96 Q.S 600

FS2 0.828

5.80 Q.S 600

FS3 0.994

5.636 Q.S 600

FS4 1.16

5.2 Q.S 600

FS5 1.326

5.31 Q.S 600

FS6 1.65

4.98 Q.S 600

FS7 2.33 4.30 Q.S 600

FS8 1.99 4.64

Q.S

600

FS9 1.83

4.80 Q.S

600

FS10 1.66 4.97

Q.S

600

FS11 1.5 5.13

Q.S

600

FS12 1.33

5.30

Q.S

600

FS13 2.86 3.77 Q.S

600

FS14 2.33 4.30 Q.S

600

FS15 1.86 4.77 Q.S

600

FS16 1.66 4.97 Q.S

600

FS17 1.53 5.10 Q.S

600

FS18 1.33 5.30 Q.S

600

FS19 0.39 6.24 Q.S 600

FS20 0.66 5.97 Q.S

600

FS21 0.79 5.84 Q.S

600

FS22 0.99 5.64 Q.S

600

FS23 1.32 5.31 Q.S

600

FS24 1.65 4.98 Q.S 600

Page 3: 7.0 Formulation and evaluation of ASA suppositories ...shodhganga.inflibnet.ac.in/bitstream/10603/15801/13/13_chapter 7.pdf128 Chapter 7 Formulation, Evaluation of ASA-suppositories

129

Chapter 7 Formulation, Evaluation of ASA-suppositories

Suppositories loaded ASA-nanoparticles

*Table representing formula for six suppositories

Table 7.2 Composition of suppositories loaded ASA nanoparticles

Formulation code Fas2 Fas4 Fas9 Fas11 Fbs1 Fbs3 Fbs4 Fbs8 Fbs11 Fbs12

Gelatin (gm)

0.828

1.16

1.83

1.5

2.86

1.86

1.66

0.66

1.32

1.65

Glycerin(gm)

5.80

5.2

4.80

5.13

3.77

4.77

4.97

5.97

5.31

4.98

Water(gm)

Q.S

Q.S

Q.S

Q.S

Q.S

Q.S

Q.S

Q.S

Q.S

Q.S

ASA

nanoparticles(mg)

600

600

600

600

600

600

600

600

600

600

*Table representing formula for one suppository

Figure 7.1 Prepared ASA-suppositories

Evaluation methods for ASA-Suppositories and suppositories loaded ASA-

nanoparticles

7.3 Appearance and physical integrity of suppositories

Appearance of the prepared ASA-suppositories and suppositories loaded ASA-

nanoparticles was evaluated with naked eye physical integrity of the suppositories was

evaluated by slicing the suppositories with stainless steel blade in to two half’s and

Page 4: 7.0 Formulation and evaluation of ASA suppositories ...shodhganga.inflibnet.ac.in/bitstream/10603/15801/13/13_chapter 7.pdf128 Chapter 7 Formulation, Evaluation of ASA-suppositories

130

Chapter 7 Formulation, Evaluation of ASA-suppositories

Suppositories loaded ASA-nanoparticles

observed to find out the presence of fissure and pits3.

7.4 Weight variation

Twenty suppositories were weighed and average weight was calculated. Each

suppository was then individually weighed by using digital balance. Not more than two

of the individual masses deviate from the average mass by more than 5% and non deviate

by more than twice4.

7.5 Mechanical Strength

The breaking strength or crushing strength was determined for measuring fragility

or brittleness of suppositories, which assess whether the suppositories will be able to

withstand the hazards of packing, transporting and normal handling or not. Suppositories

were randomLy selected and subjected for crushing using (Erweka hardness tester)4.

Figure 7.2 Erweaka hardness tester

Page 5: 7.0 Formulation and evaluation of ASA suppositories ...shodhganga.inflibnet.ac.in/bitstream/10603/15801/13/13_chapter 7.pdf128 Chapter 7 Formulation, Evaluation of ASA-suppositories

131

Chapter 7 Formulation, Evaluation of ASA-suppositories

Suppositories loaded ASA-nanoparticles

7.6 Content uniformity

Content uniformity test was determined by spectrophotometric method. The

suppository and suppositories loaded nanoparticles was individually melted, dissolved in

100 mL of phosphate buffer pH 7.2 in separate volume flask and the solution was filtered

using 0.45 µ membrane. After suitable dilution the sample was measured using U.V.

spectrometry at a wave length of 225 nm5.

7.7 Disintegration Test

The disintegration time is a critical factor in the determination of the release rate

of the active ingredient(s) from the suppository. During this test, the time taken for the

suppository to melt or disperse is measured when immersed in a water bath maintained at

constant temperature (37±10C). The time required for the suppository to melt or disperse

in the surrounding water was noted6.

7.8 Liquefaction time

Liquefaction time of the suppositories was determined based on the procedure

discussed in literature7. Glass cylinder with external diameter 50 mm, internal diameter of

20 mm and length 30 mm, two ends of the cylinder was fixed with circulating pump;

temperature of circulating medium was maintained at 37±10C. Inside the cylinder

cellophane dialyzer tubing was used to hold the suppository and then the rubber tubing

from water circulation pump was attached to one end of the glass cylinder separate

provision is provided in to the glass cylinder for thermometer arrangement7.

Page 6: 7.0 Formulation and evaluation of ASA suppositories ...shodhganga.inflibnet.ac.in/bitstream/10603/15801/13/13_chapter 7.pdf128 Chapter 7 Formulation, Evaluation of ASA-suppositories

132

Chapter 7 Formulation, Evaluation of ASA-suppositories

Suppositories loaded ASA-nanoparticles

Figure 7.3 Liquefaction assembly

7.9 Stability studies

Satiability studies were conducted based on the procedure discussed in literature,

to assess the stability of nanoparticles, suppositories and suppositories loaded

nanoparticles the samples are stores at room temperature (22⁰C - 27⁰C) and at

refrigerator conditions 5 ⁰C for three months, sampling was done at 1, 2, 3 months and

evaluated for FTIR and DSC to find out the changes during storage8.

7.10 In-vitro dissolution for ASA suppositories and suppositories loaded ASA

nanoparticles

In-vitro drug release has performed by placing the suppository in a dialysis bag

whose molecular weight was cut 10 kDa and 5 mL of dissolution medium pH 7.2

phosphate buffer and glass beads were added in to the bag and sealed and the bag was

placed in the receptor compartment containing 50 mL of phosphate buffer at 37 ± 5ºC

over a magnetic stirring at 50 rpm samples were withdrawn at regular intervals and

Page 7: 7.0 Formulation and evaluation of ASA suppositories ...shodhganga.inflibnet.ac.in/bitstream/10603/15801/13/13_chapter 7.pdf128 Chapter 7 Formulation, Evaluation of ASA-suppositories

133

Chapter 7 Formulation, Evaluation of ASA-suppositories

Suppositories loaded ASA-nanoparticles

replaced with equal amount of buffer for a period of 24 h9. The assemblage was designed

as shown in the represented in figure below.

Figure 7.4 Diagrammatic representation of suppositories and suppositories loaded

nanoparticles in-vitro drug release assemblage.

7.11 Mathematical modeling

Drug release mechanisms and kinetics are the two important characteristics of a

delivery systems in describing the drug dissolution profile. A number of mathematical

models have been developed to analyze the drug release from types of controlled release

drug delivery systems10

.

The korsmeyer-peppas power law equation predicts that the fraction release of

drug of exponentially is related to the release time and adequately describes the release of

drug from slabs, cylinders and spheres.

Page 8: 7.0 Formulation and evaluation of ASA suppositories ...shodhganga.inflibnet.ac.in/bitstream/10603/15801/13/13_chapter 7.pdf128 Chapter 7 Formulation, Evaluation of ASA-suppositories

134

Chapter 7 Formulation, Evaluation of ASA-suppositories

Suppositories loaded ASA-nanoparticles

Kinetics of in-vitro drug release

To study the release kinetics of in-vitro drug release, data was applied to kinetic

models such as zero order, first order, Higuchi and Korsmeyer- Peppas.

Zero order

Where K0 - is the zero-order rate constant expressed in units of concentration/time

t -is the time in hrs.

First order

Where C0 - is the initial concentration of drug,

K - is the first order constant

t - is the time in hrs.

Higuchi

Where Qt - is the amount of the release drug in time t,

K- is the kinetic constant and t- is time in hrs

Korsmeyer Peppas

C = K0t

LogC = LogC0 – Kt / 2.303

Qt = Kt1/2

Mt/ M∞ = Kt n

Page 9: 7.0 Formulation and evaluation of ASA suppositories ...shodhganga.inflibnet.ac.in/bitstream/10603/15801/13/13_chapter 7.pdf128 Chapter 7 Formulation, Evaluation of ASA-suppositories

135

Chapter 7 Formulation, Evaluation of ASA-suppositories

Suppositories loaded ASA-nanoparticles

Where Mt - represents amount of the released drug at time t,

M∞- is the overall amount of the drug (whole dose) released

K- is the diffusional characteristic of drug/ polymer system constant

n- is a diffusional exponent that characterizes the mechanism of release of drug.

A plot of the log (Drug released) Vs. log time yields slope “n” having the value –

n= 0.5 indicates fickian diffusion

n= 0.5 to 1 or n= 0.5 to 0.89 indicates anomalous non fickian diffusion.

In this the rate of solvent penetration and drug release are in the same range. This

deviation is due to increased drug diffusion from the matrix by the solvent induced

relaxation of the polymer.

n= 0.89 or n=1 indicates zero order release which can be achieved when

drug diffusion is rapid compared to the constant rate solvent induced

relaxation and swelling in the polymer.

Use of the power law equation to analyze the rate of drug release from a porous

system will probably lead to n > 0.5, since the combined mechanism will shift the release

exponent towards the smaller values.

Page 10: 7.0 Formulation and evaluation of ASA suppositories ...shodhganga.inflibnet.ac.in/bitstream/10603/15801/13/13_chapter 7.pdf128 Chapter 7 Formulation, Evaluation of ASA-suppositories

136

Chapter 7 Formulation, Evaluation of ASA-suppositories

Suppositories loaded ASA-nanoparticles

Table 7.3 Physiochemical evaluation results of ASA- suppositories (Fs1-Fs24)

Formulation

code

Weight

variation

(gm± S.D)

Mechanical

strength

(kg ± S.D)

Content

uniformity

(% content ±

S.D)

Disintegration

time

(minutes ± S.D)

Liquefaction

Temperature

(⁰C)

Fs1 1.01 ± 0.012 1.71 ± 0.01 95.06 ± 1.4 8.9 ± 1.7 29 ⁰C

Fs2 1.01 ± 0.013 0.88 ± 0.01 95.33 ± 1.1 8 ± 0.7 29 ⁰C

Fs3 1.004 ± 0.001 1.107 ±0.01 96.4 ± 0.5 8.5 ± 0.8 30 ⁰C

Fs4 1.06 ± 0.01 1.31 ± 0.01 96.2 ± 1 8.4 ± 1 29 ⁰C

Fs5 1.01 ± 0.01 2.11 ± 0.01 96.16 ± 1.04 10 ± 1.2 31 ⁰C

Fs6 1.02 ± 0.005 1.91 ± 0.03 93.5 ± 0.5 9 ± 1.1 31⁰C

Fs7 1.02 ± 0.005 1.53 ± 0.01 96.66 ± 2.3 8.9 ± 0.1 30 ⁰C

Fs8 1.02 ± 0.001 1.61 ± 0.02 97.66 ± 0.5 8.8 ± 0.8 30 ⁰C

Fs9 1.05 ± 0.06 0.82 ± 0.01 98.56 ± 0.5 8.2 ± 0.6 29 ⁰C

Fs10 1.01 ± 0.006 1.9 ± 0.01 97.1 ± 1 9.5 ± 1 30 ⁰C

Fs11 1.003 ± 0.007 1.61 ± 0.01 94.2 ± 1 8.7 ± 1.2 29 ⁰C

Fs12 1.002 ± 0.006 1.53 ± 0.02 95.16 ± 1.6 8.4 ± 0.3 29 ⁰C

Fs13 1.04 ± 0.02 2.3 ± 0.15 96±2 9.83±0.28 31⁰C

Fs14 1.08 ± 0.015 1.7 ± 0.1 94.6±1.5 8.6±0.57 28⁰C

Fs15 1.04± 0.03 1.6 ± 0.15 93.3±3.2 8.96±0.057 28⁰C

Fs16 1.1 ± 0.011 1.1 ± 0.1 94±2 10.1±0.17 30⁰C

Fs17 1.07 ± 0.02 1.1 ± 0.05 94.3±2.5 8.56±0.6 29⁰C

Fs18 1.06 ± 0.03 1 ± 0.05 94.4±2.25 8.23±0.25 28⁰C

Fs19 1.07 ± 0.03 0.8 ± 0.26 95.6±3.5 8.26±0.2 28⁰C

Fs20 1.05 ± 0.02 1.1 ± 0.2 94.3±3.5 8.56±0.81 28⁰C

Fs21 1.06 ± 0.04 1.2 ± 0.05 97.6±1.5 8±0.1 28⁰C

Fs22 1.05 ± 0.04 1.1 ± 0.11 96.3±2.08 8.76±0.41 28⁰C

Fs23 1.04 ± 0.05 0.7 ± 0.11 96.3±1.52 9.2±0.1 29⁰C

Fs24 1.07 ± 0.05 2.3 ± 0.05 94.3±2.3 11.06±0.8 31⁰C

Table 7.4 Physiochemical evaluation results of suppositories loaded ASA-

nanoparticles

Formulation

code

Weight

variation

(gm± S.D)

Mechanical

strength

(kg ± S.D)

Content

uniformity

(% content ±

S.D)

Disintegration

Time

(minutes ± S.D)

Liquefaction

Temperature(⁰C)

Fas2 1.02 ± 0.008 0.78 ± 0.4 82.3 ± 0.5 7.2 ± 0.3 29 ⁰C

Fas4 1.02 ± 0.004 1.10 ± 0.1 76 ± 1.1 8.1 ± 2 30 ⁰C

Fas9 1.05 ± 0.2 0.81 ± 1.2 88.9 ± 1.8 7.8 ± 1.2 29 ⁰C

Fas11 1.01 ± 0.4 1.21 ± 1.4 74.2 ± 0.8 8.5 ± 2.3 30 ⁰C

Page 11: 7.0 Formulation and evaluation of ASA suppositories ...shodhganga.inflibnet.ac.in/bitstream/10603/15801/13/13_chapter 7.pdf128 Chapter 7 Formulation, Evaluation of ASA-suppositories

137

Chapter 7 Formulation, Evaluation of ASA-suppositories

Suppositories loaded ASA-nanoparticles

Table 7.5 In-vitro characterization of suppositories loaded ASA-nanoparticles

Formulation

code

Weight

variation

(gm ± S.D)

Melting

point

(⁰C)

Disintigration

time

(minutes ±

S.D)

Mechanical

strength

(kg ± S.D)

Content

uniformity

(%content

± S.D)

Fbs1 1.03±0.01 32 8.5±0.5 1.82±0.02 67.16±1.25

Fbs3 1.04±0.0208 31 8.6±2.08 1.66±0.02 77.16±4.01

Fbs4 1.037±0.04 32 9.6±1.15 1.59±0.005 55.33±3.05

Fbs8 1.02±0.023 31 8.3±1.52 1.64±0.03 76.73±4.6

Fbs11 1.117±0.16 30 8.2±2 1.81±0.011 73.66±3.05

Fbs12 1.04±0.02 31.5 9.2±2 1.65±0.02 56.33±1.52

Table 7.6 In-vitro drug release of ASA suppositories (Fs1-Fs12)

Cumulative Percentage Drug Release

Time

(minutes)

Fs1 Fs2 Fs3 Fs4 Fs5 Fs6 Fs7 Fs8 Fs9 Fs10 Fs11 Fs12

0 0 0 0 0 0 0 0 0 0 0 0 0

5 16.4

± 0.36

21.5

± 0.5

18.5

± 0.5

21.16

±1

12.16

± 0.28

13.93

± 0.3

20.83

± 0.76

19.6

±

0.52

26.4

± 0.36

18.5

± 0.5

21.5

± 0.5

22.63

± 0.5

15 46.5± 0.5 51.4±

0.5

50±1 50.1

± 0.85

23.96

± 0.25

26.9

± 0.36

44.13

± 0.32

40.6

±

0.55

58.4

± 0.35

44.5

± 0.5

48.2±

0.6

43±1

30 72.73

± 0.64

76.56

± 0.8

73.96

± 0.95

74.83

± 0.47

47.96

± 0.05

50.3

± 0.79

62.5±

0.5

68.5

± 0.5

83±1 71.7±1.1 75.6

± 0.5

71.63

± 0.5

45 85.43

± 0.51

92

±1

88.3

± 0.60

90.6

± 0.52

82.06

± 0.2

85.43

± 0.37

87.4

± 0.51

84.8

± 0.8

94.63

± 0.55

85.16

± 0.3

87.63

± 0.5

82.63

± 0.5

60 96.5

± 0.5

98.06

±1

96.9

± 0.1

99.3

± 0.45

91.06

± 0.1

95.16

± 0.37

97.5

± 0.45

95.6

±0.55

97.6

± 1.8

97.23

± 0.49

98.7

±1.5

97

±1

Figure 7.5 In-vitro drug release of ASA suppositories (Fs1-Fs12)

0

20

40

60

80

100

120

0 20 40 60 80

Pe

rce

nta

ge r

ele

ase

Time (minutes)

Fs1Fs2Fs3Fs4Fs5Fs6Fs7Fs8Fs9Fs10Fs11

Page 12: 7.0 Formulation and evaluation of ASA suppositories ...shodhganga.inflibnet.ac.in/bitstream/10603/15801/13/13_chapter 7.pdf128 Chapter 7 Formulation, Evaluation of ASA-suppositories

138

Chapter 7 Formulation, Evaluation of ASA-suppositories

Suppositories loaded ASA-nanoparticles

Figure 7.6 In-vitro drug release of optimized formulation of ASA-suppositories.

Table 7.7 In-vitro drug release Kinetics of ASA-suppositories

(Fs1-Fs12)

Formulation

code

Krosmayer’s

Peppas

equation

n r2

Higuchis

r2

First order

K1 r2

Zero order

K0

r2

Fs1 0.722 0.986 0.992 -0.052 0.968 1.847 0.788

Fs2 0.630 0.988 0.967 -0.028 0.968 1.939 0.682

Fs3 0.679 0.973 0.990 -0.025 0.973 1.893 0.737

Fs4 0.652 0.989 0.992 -0.034 0.899 1.934 0.729

Fs5 0.852 0.990 0.958 -0.018 0.949 1.625 0.971

Fs6 0.801 0.978 0.979 -0.022 0.932 1.697 0.969

Fs7 0.638 0.997 0.996 -0.057 0.967 1.823 0.84

Fs8 0.664 0.996 0.996 -0.049 0.986 1.807 0.830

Fs9 0.548 0.984 0.980 -0.089 0.961 2.017 0.465

Fs10 0.684 0.993 0.996 -0.057 0.973 1.848 0.809

Fs11 0.629 0.993 0.994 -0.076 0.935 1.910 0.734

Fs12 0.603 0.996 0.995 -0.051 0.970 1.818 0.772

Table 7.8 In-vitro drug release study of suppositories loaded ASA-nanoparticles

0

20

40

60

80

100

120

0 20 40 60 80

Cu

mm

ilati

ve

Pe

rce

nta

ge r

ela

se

Time (minutes)

Fs2

Fs4

Fs9

Fs11

Page 13: 7.0 Formulation and evaluation of ASA suppositories ...shodhganga.inflibnet.ac.in/bitstream/10603/15801/13/13_chapter 7.pdf128 Chapter 7 Formulation, Evaluation of ASA-suppositories

139

Chapter 7 Formulation, Evaluation of ASA-suppositories

Suppositories loaded ASA-nanoparticles

Cumulative Percentage Drug release

Time

(hr) Fas2 Fas4 Fas9 Fas11

0 0 0 0 0

1 0.014±0.004 0.017±0.003 0.014±0.002 0.0663±0.08

2 19.6±1.52 18.6±1.52 22±1 16.6±1.93

4 29.63±1.51 33±1.41 33.6±1.52 26.6±0.57

8 35.4±0.52 41±1 44±2 34.2±1.31

12 55±1 51±1.73 56.6±1.52 47.6±1.52

16 68±1 62.6±1.52 67.3±1.52 58±1

20 76.8±0.98 66.6±1.52 76±1 66±1

24 82.3±1.52 71±0.85 86.4±1.63 74.06±0.9

Figure 7.7 In-vitro drug release study of ASA form suppositories loaded

nanoparticles

Table 7.9 In-vitro drug release kinetics of suppositories loaded ASA-nanoparticles

(Fas2, Fas4, Fas9, Fas11)

Formulation

code

Korsmeyer’s Peppas

equation

n r2

Higuchis

r2

First order

K1 r2

Zero order

K0

r2

Fa2 0.310 0.637 0.886 -0.030 0.988 3.866 0.899

Fa4 0.315 0.627 0.968 -0.022 0.971 3.502 0.800

Fa9 0.304 0.619 0.923 -0.035 0.969 3.340 0.851

Fa11 0.477 0.666 0.983 -0.023 0.988 3.464 0.896

0

20

40

60

80

100

0 10 20 30

Pe

rce

nta

ge r

ele

ase

Time (Hours)

Fas2

Fas4

Fas9

Fas11

Page 14: 7.0 Formulation and evaluation of ASA suppositories ...shodhganga.inflibnet.ac.in/bitstream/10603/15801/13/13_chapter 7.pdf128 Chapter 7 Formulation, Evaluation of ASA-suppositories

140

Chapter 7 Formulation, Evaluation of ASA-suppositories

Suppositories loaded ASA-nanoparticles

Table 7.10 In-vitro drug release of ASA-suppositories (Fs13-Fs24)

Cumulative Percentage Drug Release (mean ± S.D)

Time

(min)

Fs13

Fs14

Fs15

Fs16

Fs17

Fs18

Fs19

Fs20

Fs21

Fs22

Fs23

Fs24

0 0 0 0 0 0 0 0 0 0 0 0 0

5

13.66±3.21

16±2

19±1

21.3±1.52

21.3±1.52

32.6±2.2.08

26.6±1.5

24.6±1.52

23.6±1.15

21.3±1.5

29±1

20±1

10

28±1

34.6±1.5

38.6±1.5

42±2

42.6±2.08

53±2

45.6±3.05

43.3±1.52

40.6±2.08

39±1

49.3±0.5

37.6±7.5

15

40.3±1.5

44±1

49±1

51±1`

52.6±0.5

74.6±1.5

60.3±2.08

58±1

55.6±1.15

53.3±1.5

69±1

55.6±1.5

30

71±1

74.33±1.15

77±1

83.6±3.51

84.3±3.2

87.3±1.5

73.6±2.08

70±1

68.6±1.52

64.3±2.5

80±1

74.3±3.2

45

85±2

86±1

90±1

93.3±1.52

93.8±1.19

92.6±1.5

86.6±1.52

84±1

83±1

76.6±1.5

91.3±1.5

87±1

60

95±2

92±1

96.3±1.5

96.06±3.71

94.06±1.1

94.3±3.5

94.3±2.08

96.6±2.5

92.6±2.08

90.6±1.5

99±1

97±1.7

Figure 7.8 In-vitro drug releases of ASA-suppositories

(Fs13-Fs24)

0

20

40

60

80

100

120

0 20 40 60 80

Fs13

Fs14

Fs15

Fs16

Fs17

Fs18

Fs19

Fs20

Fs21

Fs22

Fs23

Fs24

Page 15: 7.0 Formulation and evaluation of ASA suppositories ...shodhganga.inflibnet.ac.in/bitstream/10603/15801/13/13_chapter 7.pdf128 Chapter 7 Formulation, Evaluation of ASA-suppositories

141

Chapter 7 Formulation, Evaluation of ASA-suppositories

Suppositories loaded ASA-nanoparticles

Figure 7.9 In-vitro dissolution results of optimized formulation ASA-suppositories

Figure 7.10 In-vitro dissolution study of optimized formulation ASA from

nanoparticles and suppositories loaded nanoparticles Fb9, Fbs23

0

20

40

60

80

100

120

0 20 40 60 80

Pe

rce

nta

ge

Cu

mila

tive

pe

rce

nta

ge r

ele

ase

Time (minutes)

Fs13

Fs15

Fs16

Fs20

Fs23

Fs24

0

10

20

30

40

50

60

70

80

0 5 10 15 20 25 30

% P

erc

en

ate

gC

um

mila

tive

pe

rce

nta

ge r

ele

ase

Time (hours)

Page 16: 7.0 Formulation and evaluation of ASA suppositories ...shodhganga.inflibnet.ac.in/bitstream/10603/15801/13/13_chapter 7.pdf128 Chapter 7 Formulation, Evaluation of ASA-suppositories

142

Chapter 7 Formulation, Evaluation of ASA-suppositories

Suppositories loaded ASA-nanoparticles

Table 7.11 In-vitro kinetics of ASA- suppositories (Fs13-Fs24)

Formulation

code

Zero order

K0 r2

First order

K1 r2

Higuchi

r2

Krosmayer’s Peppas

n r2

Fs13 1.819 0.851 -0.022 0.985 0.909 0.557 0.809

Fs14 1.824 0.747 -0.018 0.996 0.926 0.723 0.969

Fs15 1.914 0.697 -0.024 0.996 0.949 0.662 0.949

Fs16 1.969 0.588 -0.024 0.986 0.927 0.626 0.962

Fs17 1.961 0.526 -0.022 0.939 0.912 0.62 0.95

Fs18 2.026 0.49 -0.018 0.92 0.815 0.426 0.883

Fs19 1.889 0.307 -0.019 0.986 0.953 0.504 0.954

Fs20 1.87 0.486 -0.022 0.927 0.969 0.53 0.963

Fs21 1.859 0.436 -0.017 0.995 0.957 0.553 0.958

Fs22 1.729 0.552 -0.015 0.957 0.965 0.557 0.956

Fs23 2.011 0.452 -0.03 0.921 0.912 0.484 0.929

Fs24 1.903 0.611 -0.024 0.962 0.958 0.626 0.953

Table 7.12 In-vitro dissolution of suppositories loaded ASA-nanoparticles

(Fbs13, Fbs15, Fbs16, Fbs20, Fbs23, Fbs24)

Cumulative Percentage Drug release

Time(hr) Fbs13 Fbs15 Fbs16 Fbs20 Fbs23 Fbs24

0 0 0 0 0 0 0

1 0.11±0.01 0.21±0.02 0.28±0.01 0.14±0.01 0.3±0.01 0.26±0.04

2 6.5±0.5 8.066±0.15 11.86±1.59 13.2±0.81 20.6±2.5 17±1

4 12.06±0.9 11.2±0.3 21.4±1.47 18.3±0.91 25.1±0.76 24.4±1.25

8 22±1 14.6±0.5 29.4±1.44 33.3±2.5 44±1 33.3±1.52

12 31.8±0.76 24.96±0.65 37.06±1.05 41.3±2.5 57±1 42.83±2.25

16 37.8±0.28 31±0.8 40.73±0.55 46.3±3.05 64.9±0.85 52±1

20 42.16±1.04 36.13±0.3 46.6±1.55 52.6±1.52 67.33±1.5 60±1

24 51.16±0.76 40.46±0.47 53.06±2 56±1 72.13±1.8 63.83±1.25

Page 17: 7.0 Formulation and evaluation of ASA suppositories ...shodhganga.inflibnet.ac.in/bitstream/10603/15801/13/13_chapter 7.pdf128 Chapter 7 Formulation, Evaluation of ASA-suppositories

143

Chapter 7 Formulation, Evaluation of ASA-suppositories

Suppositories loaded ASA-nanoparticles

Figure 7.11 In-vitro drug release study of ASA form suppositories loaded

nanoparticles

Table 7.13 In-vitro kinetics of suppositories loaded ASA-nanoparticles

(Fbs13, Fbs15, Fbs16, Fbs20, Fbs23, Fbs24)

Formulation

code

Zero order

K0 r2

First order

K1 r2

Higuchi

r2

Krosmayer’s Peppas

n r2

Fbs13 2.098 0.986 0.029 -0.996 0.998 1.984 0.886

Fbs15 1.667 0.984 0.021 -0.993 0.989 1.597 0.861

Fbs16 2.027 0.962 0.029 -0.984 0.990 1.693 0.856

Fbs20 2.225 0.954 0.033 -0.978 0.989 1.947 0.851

Fbs23 2.975 0.946 0.056 -0.986 0.986 1.831 0.863

Fbs24 2.561 0.970 0.042 -0.991 0.991 1.826 0.837

0

10

20

30

40

50

60

70

80

0 5 10 15 20 25 30

% C

DR

Time (Hours)

Fbs13

Fbs15

Fbs16

Fbs20

Fbs23

Fbs24