design and characterization of...

Results

Ph.D. Thesis 16

5. RESULTS

5.1 Okra gum

5.1.1 Phytochemical examination

Table 4.1 Chemical tests for phytochemical examination of okra gum

powder

Tests Observations Inference

Ruthenium red test Red color Mucilage

Molisch test

Purple ring at the interface

between the acid and test

layers

Carbohydrate

Ninhydrin test No Blue to blue-violet color Absence of amino acid

Test for

reducing

sugars

Benedict's reagent Blue to

green/yellow/orange/red/brown Reducing sugars

Fehling I Brick red precipitate Reducing sugars

Fehling II

5.1.2 Physicochemical characterization

Table 4.2 Physicochemical properties of okra gum powder

Parameters Okra gum

Solubility

Slightly soluble in water.

Practically insoluble in ethanol,

acetone and chloroform

Swelling index

pH 1.2 2.25 ± 0.2

pH 7.4 2.38 ± 0.3

pH 6.8 2.15 ± 0.2

Distilled water 2.22 ± 0.5

Loss on drying 0.89 ± 0.01%

Total ash 1.8 ± 0.03%

Acid insoluble ash 0.6 ± 0.03%

Angle of repose 32 ± 0.110

pH 6.8 ± 0.54

Bulk density 0.72 ± 0.021g/cm3

Tapped density 0.84 ± 0.031g/cm3

Compressibility index 14.3 ± 0.014%

Hausner's ratio 1.16 ± 0.014

Results

Ph.D. Thesis Page 117

5.1.3 Instrumental analysis

Thermo gravimetric analysis (TGA)

Figure 2.1 TGA thermogram of OG

Differential scanning calorimetry (DSC)

Figure 2.2 DSC thermogram of OG

Results


Fourier transform-infra red (FT-IR)

Figure 2.3 FT-IR spectrum of OG

X-ray powder diffraction (XRPD)

Figure 2.4 X-ray pattern of OG

Results


Particle size analysis of OG

Figure 2.5 Particle size analysis of OG

Elemental analysis

The quantitative elemental analysis showed that gum of OG contains 37.02,

6.64 and 2.65% of carbon, hydrogen and nitrogen, respectively.

Morphological study

Figure 2.6 Scanning electron micrograph of OG

Results


5.1.4 Functional property

pH change study

Figure 2.7 pH change study (Test-with OG, Control-without OG)

Results


5.2 Theophylline

5.2.1 Identification of drug

a) Melting point study

Melting point of Theophylline was found to be 272ºC which is in accordance

with the standard melting point of Theophylline (270-274 as per B.P)

b) IR spectroscopy study

The major peaks obtained in the infra red spectra are shown in table.

Figure 2.8 IR spectrum of Theophylline

Table 4.3 Data of IR with vibrations and its frequency

Vibrations Frequency

(cm-1

)

N-H stretching 3441.99

Saturated ketone C=O stretching 1717.06

Unsaturated ketone C=O stretching 1666.83

Aromatic C=C stretching 1566.21

C-N stretching 1484.61

C-H stretching 1444.72

Aromatic C-N bending 1284.86

C-O stretching 1240.98

This is in accordance with standard IR spectrum of Theophylline.

Results


5.2.2 Preformulation study by DSC

Drug-excipients compatibility study DSC

Figure 2.9 DSC thermogram of Theophylline

Figure 2.10 DSC thermogram of prepared matrix tablet of Theophylline

Results


5.2.3 Method of estimation of drug

a) Determination of λ max of Theophylline in phosphate buffer saline, pH 6.8.

Figure 2.11 Scanning spectrum of Theophylline between 200-400nm in

phosphate buffer saline, pH 6.8

Table 4.4 Linearity of Theophylline in different media

Concentration

(μg/mL)

UV Absorbance in different media

0.1N HCl

pH 1.2

Phosphate

buffer saline

pH 7.4

Phosphate

buffer saline

pH 6.8

2.5 0.127 0.126 0.125

5 0.273 0.2705 0.268

10 0.544 0.554 0.564

15 0.816 0.8135 0.811

20 1.087 1.0795 1.072

R square 0.999 0.999 0.998

Slope 0.054 0.054 0.054

Intercept 0.004 0.002 0

Results


Figure 2.12 Standard calibration curve of Theophylline in 0.1N HCl,

pH 1.2

Figure 2.13 Standard calibration curve of Theophylline in phosphate

buffer saline, pH 7.4

Results


Figure 2.14 Standard calibration curve of Theophylline in phosphate

buffer saline, pH 6.8

Results


5.2.4 Evaluation of Theophylline matrix tablets

A comparative study of physical properties of matrix tablets

Table 4.5 Properties of granules used to prepare matrix tablets containing

Theophylline

Code

Angle of

repose

(θ0)

Bulk density

(g/mL)

Tapped

density

(g/mL)

CI

(%) HR

F1 51.78 ± 1.7 0.280 ± 0.011 0.345 ± 0.013 18.84 ± 0.2 1.23

F2 47.70 ± 0.8 0.234 ± 0.011 0.371 ± 0.011 36.92 ± 0.6 1.61

F3 48.61 ± 2.7 0.355 ± 0.021 0.541 ± 0.012 34.38 ± 0.6 1.52

F4 63.40 ± 1.2 0.266 ± 0.022 0.533 ± 0.014 50.09 ± 0.4 2.00

F5 56.74 ± 0.4 0.264 ± 0.012 0.542 ± 0.013 51.29 ± 0.4 2.05

F6 47.64 ± 1.2 0.224 ± 0.012 0.354 ± 0.013 36.72 ± 0.5 1.58

CI- Carr’s index, HR-Hausner’s ratio

Table 4.6 Physical properties of matrix tablets of Theophylline

Code

Weight

variation

(mg)

Hardness

(kg/cm²)

Friability

(%)

Drug

Content

(%)

F1 500 ± 1.23 4.50 ± 0.67 0.74 98.34

F2 500 ± 2.43 4.00 ± 0.98 0.78 99.34

F3 500 ± 2.16 4.50 ± 0.46 0.76 99.15

F4 500 ± 1.49 4.00 ± 0.23 0.77 97.56

F5 500 ± 1.32 4.25 ± 0.16 0.73 97.75

F6 500 ± 2.42 4.50 ± 0.66 0.73 98.77

Results

Ph.D. Thesis 7

Table 4.7 Swelling study of matrix tablets of Theophylline (F1 to F4 & F6)

Time

(h)

% Swelling

F1 F2 F3 F4 F6

0 0 0 0 0 0

1 10± 1.3 95± 2.7 90± 2.6 100± 3.4 20± 1.9

2 30± 3.1 165±6.4 95± 3.1 180± 3.6 31± 2.2

3 40± 2.6 200± 7.8 97± 4.2 200± 4.6 85± 3.1

4 45± 2.7 230± 8.1 100± 4.2 250± 5.4 110± 3.5

5 75±3.2 286± 8.5 105± 4.1 300± 5.3 170± 4.1

6 102± 2.7 364± 7.2 112± 4.6 370± 5.1 230± 4.6

Figure 2.15 Swelling study of matrix tablets of Theophylline (F1 to F4, F6)

Results


Figure 2.16 Photographic images of swelling study (after 1h)

Table 4.8 Erosion study of matrix tablets of Theophylline (F1 to F4 & F6)

Time

(h) (%) Erosion

F1 F2 F3 F4 F6

0 0 0 0 0 0

1 20 ± 1.3 10 ± 1.1 10 ± 1.1 6 ± 0.7 8 ± 0.88

2 30 ± 2.6 12 ± 1.5 18 ± 1.4 10 ± 0.8 10 ± 0.97

3 35 ± 2.2 20 ± 1.6 26 ± 1.6 15± 1.1 15 ± 1.6

4 48 ±3.1 25 ± 1.8 37 ± 2.4 23 ± 1.5 16 ± 1.5

5 53 ± 2.5 26 ± 1.6 44 ± 2.1 26 ± 1.8 18 ± 1.8

6 58 ± 2.8 27 ± 1.5 51 ± 3.1 28 ± 2.4 21 ± 2.2

Figure 2.17 Erosion study of matrix tablets of Theophylline (F1 to F4, F6)

Results


Table 4.9 In vitro drug release study of matrix tablets of Theophylline for

5h (F1 to F4 &F6)

Time

(h)

Cumulative percentage drug release

F1 F2 F3 F4 F6

0 0 0 0 0 0

1 10.05 ± 2.1 30.17 ± 2.1 24.15 ± 2.2 30.68 ± 0.9 13.10 ± 1.1

2 14.25 ± 1.2 38.16 ± 2.1 34.15 ± 2.5 46.36 ± 1.1 19.45 ± 1.5

3 19.45 ± 3.1 46.74 ± 1.3 40.12 ± 2.6 57.72 ± 1.1 34.15 ± 2.2

4 29.45 ± 0.9 57.15 ± 1.6 47.15 ± 1.6 63.09 ± 1.3 42.13 ± 2.6

5 46.78 ± 0.9 60.54 ± 1.4 61.42 ± 1.1 72.82 ± 1.6 51.42 ± 2.4

Figure 2.18 Comparative dissolution profiles of prepared matrix tablets of

Theophylline for 5h (F1 to F4, F6)

Results


A preliminary intact study of matrix tablets of natural polymers

Preparation of matrix tablets by direct compression method

Table 4.10 Physical properties and intact study of prepared matrix tablets

(IS1-IS4)

Code

Weight

variation

(mg)

Hardness

(Kg/cm2)

Intact study in 0.1N HCl (pH 1.2)

After 5 min After 10 min After 30 min

IS1 700 ± 3.5 2.5 ± 0.12 Erosion in layers Erosion in

layers

Complete

erosion

IS2 700 ± 3.1 2.1 ± 0.11 Extensive swelling Complete

erosion -

IS3 700 ± 2.3 2.4 ± 0.13

Extensive swelling

and complete

erosion

- -

IS4 700 ± 3.9 2.3 ± 0.11 Disintegrated

completely

Complete

erosion -


(IS5-IS10)

Code

Weight

variation

(mg )

Hardness

(Kg/cm2)


After 5 min After 10 min

IS5 700 ± 2.5 2.4 ± 0.11 Extensive swelling and

complete erosion -

IS6 700 ± 3.1 2.4 ± 0.12 Extensive swelling and

complete erosion -

IS7 700 ± 3.3 2.6 ± 0.12 Complete

disintegration -

IS8 700 ± 3.2 2.1 ± 0.13 Swelling and erosion

simultaneously Complete erosion





Results



(IS11-IS18)

Code

Weight

variation

(mg )

Hardness

(Kg/cm2)


After 5 min After 10 min After 30 min


simultaneously

Complete

erosion -


simultaneously

Complete

erosion -


simultaneously

Complete

erosion -

IS14 700 ± 3.1 2.2 ± 0.11 Erosion in layers Complete

erosion -

IS15 700 ± 2.5 2.5 ± 0.13 Erosion in layers Complete

erosion -

IS16 700 ± 2.3 2.4 ± 0.14 Complete

disintegration - -

IS17 700 ± 2.4 2.5 ± 0.16 Erosion in layers Erosion in

layers

Complete

erosion

IS18 700 ± 2.6 2.5 ± 0.11 Swelling and

simultaneous erosion

Erosion in

layers

Complete

erosion

Results


Preparation of matrix tablets by wet granulation method


(IS19-IS22)

Code

Weight

variation

(mg)

Hardness

(kg/cm2)

Intact study

Simulated gastric fluid

(after 2h)

Simulated intestinal

fluid

(after 5h)

IS19 700 ± 2.5 3.7 ±0.66 No swelling with very

slight erosion

Sight erosion with

bubble formation

IS20 700 ± 2.3 3.7 ± 0.67 Immediate extensive

swelling

Completely

disintegration

IS21 700 ± 2.0 4.1 ± 0.48 Immediate extensive

swelling Complete disintegration

IS22 700 ± 2.4 4.2 ± 0.39 Immediate erosion and

Complete disintegration -


(IS23-IS33)

Code Weight

(mg)

Hardness

(kg/cm2)

Intact study

Simulated gastric fluid

(after 2h)

Simulated intestinal fluid

(after 5h)

IS23 700 ± 2.5 4.1 ± 0.34 Immediate


IS24 700 ± 2.4 4.2 ± 0.34 Immediate


IS25 700 ± 2.6 3.9 ± 0.45 Complete

disintegration -

IS26 700 ± 3.1 3.5 ± 0.24 Swelling at

slower rate Complete disintegration

IS27 700 ± 2.5 3.4 ± 0.22 Swelling at

slower rate Complete disintegration

IS28 700 ± 2.4 3.7 ± 0.14 Complete

disintegration -

IS29 700 ± 2.5 4.1 ± 0.36 slow erosion Slow

gradual erosion

IS30 700 ± 2.4 3.8 ± 0.45 slow erosion No swelling

Slight gradual erosion

IS31 700 ± 3.5 3.9 ± 0.54 Complete

disintegration -

IS32 700 ± 3.1 4.1 ± 0.34 slight erosion Slight erosion with

continuous bubbling

IS33 700 ± 2.9 4.5 ± 0.33 slight erosion Slight erosion with

continuous bubbling

Results


Table 4.15 Drug release upto 5h (intact study) of prepared matrix tablets

(IS19-IS33)

Code

Cumulative percentage

drug release

SGF

(%)

SIF

(%)

IS19 2.11 8.89

IS20 37.0 53.0

IS21 39.0 55.0

IS22 101.24 -

IS23 25.0 51.0

IS24 30.0 53.0

IS25 99.16 -

IS26 16.0 51.0

IS27 20.0 53.0

IS28 102.11 -

IS29 4.31 10.31

IS30 3.48 10.41

IS31 98.24 -

IS32 2.32 10.12

IS33 2.10 10.60

SGF-Simulated gastric fluid

SIF-Simulated intestinal fluid


(IS34-IS36)

Code

Weight

variation

(mg)

Hardness

(kg/cm2)

Intact study

Simulated

gastric fluid

(after 2h)


(after 5h)

IS34 500 ± 3.4 3.7 ± 0.54 Slow erosion Erosion with continuous

bubbling

IS35 600 ± 2.5 4.2 ± 0.34 No swelling, No

erosion

No swelling No erosion only

bubble formation

IS36 700 ± 3.4 4.4 ± 0.22 No swelling. No

erosion


bubble formation

Results



(IS37-IS39)

Code

Weight

variation

(mg)

Hardness

(kg/cm2)

Intact study

Simulated

gastric fluid

(after 2h)


(after 5h)

IS37 500 ± 2.1 4.2 ± 0.42 Slow erosion Erosion with continuous

bubbling

IS38 600 ± 3.2 4.4 ± 0.33 No swelling, No

erosion


bubble formation

IS39 700 ± 3.1 4.5 ± 0.35 No swelling. No

erosion


bubble formation

Table 4.18 Drug release upto 5h (intact study) of prepared matrix tablets

(IS34-IS39)

Code

Cumulative percentage

drug release

SGF

(%)

SIF

(%)

IS34 8.47 21.11

IS35 11.34 27.13

IS36 1.79 4.56

IS37 3.26 10.11

IS38 1.98 3.36

IS39 1.1 2.21

Results


Preparation of matrix tablets by wet granulation method for colon specific

drug delivery

Table 4.19 Physical properties of matrix tablets containing various

concentrations of OG using 3.0% PVPK30 (OG1-OG3)

Code

Weight

variation

(mg)

Hardness

(kg/cm2)

Friability

(%)

Drug

content

(%)

Rel 5h

(%)

OG1 415 ± 2.24 3.1 ± 0.67 0.64 98.12 92.64

OG2 515 ± 2.15 3.6 ± 0.64 0.34 101.31 81.24

OG3 615 ± 3.12 3.4 ± 0.37 0.35 101.24 64.35

Rel5h-Drug release for 5h of dissolution



(Granulation was done using 60# sieve)

Code Weight variation

(mg)

Hardness

(kg/cm2)

Friability

(%)

Drug

content

(%)

Rel 5h

(%)

OG4 415 ± 1.15 4.24 ± 0.34 0.64 96.35 88.64

OG5 515 ± 1.26 4.24 ± 0.45 0.47 97.97 76.84

OG6 615 ± 1.13 4.26 ± 0.26 0.51 98.67 60.31




Code

Weight

variation

(mg)

Hardness

(kg/cm2)

Friability

(%)

Drug

content

(%)

Rel 5h

(%)

OG7 400 ± 2.23 4.25 ± 0.34 0.84 97.78 84.11

OG8 500 ± 1.45 5.11 ± 0.10 0.89 98.94 45.71

OG9 600 ± 1.34 5.46 ± 0.20 0.88 101.11 31.73

OG10 630± 1.31 5.54± 0.30 0.67 102.10 27.74


Results




Code

Weight

variation

(mg)

Hardness

(kg/cm2)

Friability

(%)

Drug

content

(%)

Rel 5h

(%)

OG11 415± 3.23 4.25 ± 0.11 0.84 98.70 89.64

OG12 515± 3.45 4.50 ± 0.10 0.89 97.17 71.31

OG13 615± 3.34 4.50 ± 0.30 0.88 96.45 55.84


Table 4.23 In vitro dissolution study of prepared matrix tablets (OG7-OG10)

Time

(h)

Cumulative percentage release

OG7 OG8 OG9 OG10

Control With

RC Control

With

RC Control

With

RC Control

With

RC

0 0 0 0 0 0 0 0 0

1 24.16 25.34 17.50 18.32 9.61 10.41 8.84 9.45

2 32.15 31.24 29.62 30.41 16.12 16.92 12.84 14.54

3 55.45 53.24 35.44 35.45 21.11 21.83 21.71 22.12

4 67.14 68.34 40.55 40.54 24.41 26.12 22.12 23.53

5 84.11 86.48 45.71 45.56 31.73 32.62 27.74 28.52

6 100.1 100.2 55.86 77.15 37.36 55.11 32.31 37.57

7 - - 62.72 92.94 45.36 72.22 43.65 60.82

8 - - 70.53 101.2 56.71 88.83 51.84 88.32

f2

value 84.92 30.92 32.13 34.56

RC- rat caecal

Results


Figure 2.19 Comparative dissolution profiles of prepared matrix tablets

(OG7-OG10)

Figure 2.20 Photographs of matrix tablets (OG8, OG9 & OG10) during

dissolution

Results



Time

(h)


OG11 OG12 OG13

Control With

RC Control

With

RC Control With RC

0 0 0 0 0 0 0

1 30.16 29.19 21.50 18.32 15.61 13.41

2 41.24 42.24 29.62 30.41 21.12 18.92

3 62.45 63.24 39.44 37.45 31.11 32.83

4 77.14 76.34 54.55 54.54 44.41 46.12

5 89.64 86.89 71.31 73.14 55.84 56.22

6 100.1 100.2 78.86 86.15 67.36 79.11

7 - - 89.24 101.12 75.36 92.22

8 - - 100.31 - 86.71 102.83

f2

value 87.34 48.44 44.13

RC-Rat caecal


with or without RC (OG11-OG13)

Results


Table 4.25 Physical properties of tablet formulations containing

combinations of OG and other polymers using 3.5%

PVPK30 (OG14-OG23)

Code

Weight

variation

(mg)

Hardness

(kg/cm2)

Friability

(%)

Drug

content

(%)

Rel 5h

(%)

OG14 700 ± 1.3 4.11 ± 0.84 0.69 97.78 40.88

OG15 700 ± 1.4 3.25 ± 0.78 0.67 99.46 45.12

OG16 700 ± 1.2 3.34 ± 0.64 0.47 98.78 101.20

OG17 700 ± 1.4 4.67 ± 0.67 0.54 99.47 38.42

OG18 700 ± 2.1 5.2 ± 0.54 0.45 101.2 32.37

OG19 700 ± 1.3 4.2 ± 0.49 0.57 99.47 60.27

OG20 700 ± 1.4 4.6 ± 0.67 0.47 101.4 34.36

OG21 700 ± 2.1 5.1 ± 0.97 0.64 99.45 32.12

OG22 700 ± 1.3 4.3 ± 0.87 0.89 97.45 40.12

OG23 700 ± 2.1 5.3 ± 0.67 0.56 96.15 29.14

Rel 5h-Drug release for 5h of dissolution


Time

(h)


OG21 OG22 OG23

With RC Control With RC Control With RC Control

0 0 0 0 0 0 0

1 8.89 8.12 12.34 11.34 10.2 9.14

2 13.24 13.24 17.34 18.24 15.24 15.15

3 17.64 16.54 24.36 22.34 19.22 17.34

4 24.22 23.11 32.18 31.14 24.35 22.34

5 32.12 31.24 40.12 41.29 29.14 28.34

6 55.34 37.45 59.64 48.34 58.64 34.25

7 82.34 48.24 78.34 65.24 83.54 43.51

8 91.21 57.34 88.11 71.24 94.14 54.24

f2 value 29.53 44.79 25.57

RC-Rat caecal

Results



(OG21-OG23)

Table 4.27 Physical properties of tablet formulations as per the simplex

lattice design using 3.5% PVPK30 (SD01-SD14)

Code

Weight

variation

(mg)

Hardness

(Kg/cm2)

Friability

(%)

Rel5h

(%)

SD01 600 ± 0.12 4.5 ± 0.09 0.580 44.35

SD02 600 ± 0.84 4.0 ± 0.05 0.410 42.31

SD03 600 ± 0.45 4.5 ± 0.04 0.400 38.98

SD04 600 ± 0.24 4.0 ± 0.06 0.781 44.56

SD05 600 ± 0.23 3.5 ± 0.09 0.871 48.35

SD06 600 ± 0.05 3.5 ± 0.07 0.714 41.21

SD07 600 ± 0.66 4.0 ± 0.04 0.718 42.12

SD08 600 ± 0.24 4.5 ± 0.06 0.667 52.11

SD09 600 ± 0.21 4.0 ± 0.08 0.541 56.34

SD10 600 ± 0.14 5.0 ± 0.04 0.642 40.11

SD11 600 ± 0.24 4.5 ± 0.05 0.580 44.12

SD12 600 ± 0.22 4.0 ± 0.06 0.600 38.44

SD13 600 ± 0.31 4.5 ± 0.07 0.620 43.33

SD14 600 ± 0.14 4.0 ± 0.09 0.670 41.11


Results


Table 4.28 ANOVA for quadratic model (Rel5h) (SD01-SD14)

Source Sum of

Squares DF

Mean

Square

F

Value

p-value

Prob> F Inference

Model 177.99 5 35.60 2.07 0.0001 significant

Linear Mixture 53.80 2 26.90 1.57 0.0007

AB 94.84 1 94.84 5.52 < 0.0001

AC 16.26 1 16.26 0.95 0.0036

BC 9.77 1 9.77 0.57 0.3090

Residual 137.39 8 17.17

Lack of Fit 34.65 4 8.33 0.34 0.0005 significant

Pure Error 102.73 4 26.68

Cor Total 315.38 13

Figure 2.23 A Normal probability plot (Rel5h) (SD01-SD14)

Results


Figure 2.24 A Contour plots for simplex lattice design (Rel5h) (SD01-SD14)

Figure 2.25 A Surface plots for simplex lattice design (Rel5h) (SD01-SD14)

Design-Expert® Software

Component Coding: Actual

Highs/Lows inverted by U_Pseudo coding

Lag phase

Design Points

X1 = A: OG

X2 = B: HPMC

X3 = C: MCC

A: OG

250.000

B: HPMC

50.000

C: MCC

0.000

50.000 100.000

300.000

Lag phase

40.950142.7517

42.751744.5533

44.5533

46.3548

48.1564

2

2 2

2

Design-Expert® SoftwareComponent Coding: ActualHighs/Lows inverted by U_Pseudo codingLag phase

Design points above predicted valueDesign points below predicted value

X1 = A: OGX2 = B: HPMCX3 = C: MCC

A (250.000) B (100.000)C (0.000)

35

40

45

50

55

60

Lag

pha

se

A (300.000)

B (50.000)

C (50.000)

Results


Table 4.29 In vitro dissolution study of prepared matrix tablets (SD01-SD07)

Time

(h)


SD01 SD02 SD03 SD04 SD05 SD06 SD07

0 0

0 0 0 0 0

1 4.5 4.2 9.45 15.34 8.64 10.21 3.87

2 8.50 8.20 15.34 21.51 15.34 18.45 8.41

3 20.31 18.34 19.34 26.34 24.39 27.38 19.37

4 31.24 29.34 28.34 32.34 34.18 36.84 32.66

5 44.35 42.31 38.98 44.56 48.35 41.21 42.12

6 - - 47.37 - - - -

7 - - 68.34 - - - -

8 - - 94.18 - - - -

Table 4.30 In vitro dissolution study of prepared matrix tablets (SD08-SD14)

Time

(h)


SD08 SD09 SD10 SD11 SD12 SD13 SD14

0 0 0 0 0 0 0 0

1 10.34 3.84 8.24 3.54 8.97 4.25 9.67

2 19.22 8.47 16.12 6.50 15.14 9.10 18.12

3 27.38 23.34 22.34 18.37 21.24 19.34 24.34

4 41.24 40.66 30.24 31.11 30.14 31.24 33.67

5 52.11 56.34 40.11 44.12 38.44 43.33 41.11

6 - - - - 47.24 - -

7 - - - - 71.24 - -

8 - - - - 96.67 - -

Results



(SD01-SD14)


concentrations of OG (OG24-OG29)

Code

Weight

variation

(mg)

Hardness

(kg/cm2)

Friability

(%)

Drug

content

(%)

Rel 5h

(%)

OG24 500±1.2 3.4±0.14 0.34 101.35 42.35

OG25 600±1.2 4.1±0.11 0.36 101.46 38.64

OG26 700 ± 1.3 3.8 ± 0.16 0.24 96.31 16.64

OG27 600 ± 1.4 4.0 ± 0.15 0.29 98.66 12.21

OG28 600 ± 2.1 4.2 ± 0.18 0.22 102.1 32.54

OG29 600 ± 2.1 4.5 ± 0.11 0.26 102.3 20.33


Results



Time

(h)


OG24 OG25

With RC Control With RC Control

0 0 0 0 0

1 11.34 12.34 11.11 10.21

2 18.34 19.24 17.64 17.21

3 28.45 28.34 24.15 25.35

4 34.51 35.24 30.21 32.21

5 41.24 42.35 37.37 38.64

6 65.34 53.64 58.34 48.57

7 77.24 62.34 72.24 57.52

8 94.25 70.24 91.24 66.65

f2 value 40.71 40.92

RC-Rat caecal


Time

(h)


OG26 OG27


0 0 0 0 0

1 5.56 5.14 4.24 4.41

2 9.64 8.45 7.15 8.12

3 12.31 12.45 9.34 10.64

4 14.21 13.24 11.54 11.24

5 17.68 16.64 13.21 12.21

6 38.64 27.25 37.35 26.34

7 58.63 40.34 57.25 38.64

8 86.24 55.24 84.25 52.24

f2 value 36.16 35.66

RC- Rat caecal

Results


Table 4.34 In vitro dissolution of prepared matrix tablets (OG28-OG29)

Time

(h)


OG28 OG29


0 0 0 0 0

1 7.46 8.64 7.21 6.89

2 14.25 13.24 10.10 9.34

3 19.64 20.34 13.24 14.34

4 25.35 26.35 16.24 17.34

5 31.24 32.54 21.21 20.33

6 46.35 39.31 38.21 29.29

7 64.25 48.35 64.25 46.26

8 88.24 58.63 83.55 55.34

f2 value 38.21 38.03

RC-Rat caecal


(OG24-OG29)

Results


Table 4.35 Physical properties of matrix tablets prepared by factorial

design for OG and GG (FS1-FS9)

Code

Weight

variation

(mg)

Hardness

(Kg/cm2)

Friability

(%)

Drug

content

(%)

FS1 450±1.24 4.25 ± 0.22 0.58 101.2

FS2 500±1.25 4.30 ± 0.32 0.57 101.1

FS3 550±1.44 4.36 ± 0.13 0.54 99.35

FS4 500±1.26 4.55 ± 0.14 0.64 98.78

FS5 550±0.99 4.67 ± 0.21 0.64 99.45

FS6 600±1.27 4.68 ± 0.12 0.45 101.4

FS7 550±1.46 4.77 ± 0.24 0.56 100.5

FS8 600±1.34 5.01 ± 0.11 0.55 97.80

FS9 650±1.25 4.23 ± 0.32 0.34 98.89

Table 4.36 In vitro dissolution study of prepared matrix tablets (FS1-FS9)

Time

(h)


FS1 FS2 FS3 FS4 FS5 FS6 FS7 FS8 FS9

0 0 0 0 0 0 0 0 0 0

1 20.13 17.17 16.97 16.11 14.53 14.53 13.58 10.42 8.05

2 24.30 24.27 20.32 19.44 19.42 17.85 16.10 12.12 9.72

3 30.49 28.48 26.46 22.81 22.80 22.78 18.64 15.41 11.41

4 38.72 36.69 30.70 27.80 24.62 24.61 19.64 17.15 12.32

5 43.09 41.04 34.98 32.84 29.63 28.03 21.43 18.13 13.24

6 65.26 61.22 49.18 47.40 42.58 40.96 36.66 34.90 20.49

7 85.71 85.56 65.50 62.13 60.41 50.88 46.53 40.02 30.19

8 92.55 90.44 89.89 89.64 86.32 79.85 70.71 69.66 62.88

Results



(FS1-FS9)

Table 4.37 In vitro dissolution parameters of prepared matrix tablets

(FS1-FS9)

Parameters FS1 FS2 FS3 FS4 FS5 FS6 FS7 FS8 FS9

Rel5h (%) 43.09 41.04 34.98 32.84 29.63 28.03 21.43 18.13 13.24

Rel8h (%) 92.55 90.44 89.89 89.64 86.32 79.85 70.71 69.66 62.88

Rel5h= Drug release for 5h of dissolution, Rel8h= Drug release for 8h of dissolution

Table 4.38 Release kinetics study for prepared matrix tablets (FS1-FS9)

Code

R square

n k Zero

order

First

order Matrix Peppas

Hixon

Crowell

FS1 0.9739 0.8947 0.9182 0.9337 0.9353 0.6768 18.6706

FS2 0.9726 0.8909 0.9090 0.9419 0.9294 0.7136 16.9898

FS3 0.9558 0.8331 0.8874 0.9136 0.889 0.6609 16.1005

FS4 0.9471 0.8161 0.8644 0.8989 0.8722 0.6877 14.3632

FS5 0.9366 0.8209 0.8518 0.8897 0.8691 0.6848 13.6371

FS6 0.9344 0.8388 0.8628 0.8924 0.8790 0.6431 13.6989

FS7 0.9201 0.8529 0.8333 0.8464 0.8798 0.6508 11.1592

FS8 0.9045 0.8249 0.7990 0.8606 0.8648 0.7458 8.5024

FS9 0.8375 0.76.18 0.7243 0.8057 0.7682 0.7199 6.7681

Results


Figure 2.29 Surface plot for rel5h (FS1-FS9)

Figure 2.30 Surface plot for rel8h (FS1-FS9)

Results


5.2.5 In vivo pharmacokinetic study of some selected formulations of

Theophylline (OG10, OG27 and FS9)

Figure 2.31 HPLC chromatogram of blank rabbit plasma

Figure 2.32 HPLC chromatogram of rabbit plasma sample spiked with

Theophylline and caffeine (internal standard)

Results


Table 4.39 Calibration curve of Theophylline in rabbit plasma

Sr. No. Concentration

(g/mL)

Peak area of

Theophylline

(mV/sec)

Peak area of

caffeine

(mV/sec)

Peak area ratio of

Theophylline/caffeine

1 0.5 43520 959480 0.045357902

2 2.5 193960 1004986 0.192997713

3 5 323625 769103 0.420782392

4 10 679176 978692 0.693962963

5 25 1898411 1110186 1.709993641

Figure 2.33 Calibration curve of Theophylline in rabbit plasma

Results


Table 4.40 In vivo pharmacokinetic Study of orally administered matrix

tablet (OG10) and Theo SR (Marketed formulation) to three

rabbits under fasted conditions (n=3)

Time

(h)

Plasma concentration

(µg/mL)

OG10 Marketed

formulation

0 0 0

1 4.45±1.30 6.45 ± 1.31

2 7.12±1.25 8.12 ± 1.23

3 9.11±1.34 9.11 ± 1.89

4 12.55±1.48 20.12 ± 2.34

5 13.64±1.81 18.45 ± 2.64

6 16.45±1.97 16.45 ± 2.33

8 12.33±2.03 10.11 ± 1.8

AUC

(μg·h/mL) 84.11 97.04

Figure 2.34 Plasma concentration profiles of orally administered matrix


rabbits under fasted conditions. Each value represents mean

± S.D. (n=3)

Results





Time

(h)


(µg/mL)

OG27 Marketed

formulation

0 0 0

1 1.91 ± 0.86 6.45 ± 1.31

2 2.25 ± 0.91 8.12 ± 1.23

3 4.55 ± 1.01 9.11 ± 1.89

4 7.61 ± 1.24 20.12 ± 2.34

5 19.24 ± 1.96 18.45 ± 2.64

6 14.42 ± 1.92 16.45 ± 2.33

8 13.44 ± 1.84 10.11 ± 1.8

AUC

(μg·h/mL) 70.40 97.04




± S.D. (n=3)

0

4

8

12

16

20

0 2 4 6 8

Co

nce

ntr

ati

on

(m

cg/m

l)

Time (h)

OG27 MF

Results



tablet (FS9) and Theo SR (Marketed formulation) to three


Time

(h)


(µg/mL)

FS9 Marketed

formulation

0 0 0

1 2.26 ± 1.60 6.45 ± 1.31

2 4.55 ± 1.45 8.12 ± 1.23

3 5.11 ± 1.54 9.11 ± 1.89

4 11.55 ± 1.36 20.12 ± 2.34

5 20.31 ± 1.50 18.45 ± 2.64

6 17.23 ± 2.00 16.45 ± 2.33

8 14.22 ± 2.01 10.11 ± 1.8

AUC

(μg·h/mL) 83.75 97.04


tablet (FS9) and Theo SR (Marketed Formulation) to three


± S.D. (n=3)

0

5

10

15

20

25

0 2 4 6 8

con

cen

tra

tio

n (

mcg

/ml)

Time (h)

FS9 MF

Results


Table 4.43 In vivo pharmacokinetic parameters for optimized formulations

Parameters Prepared formulations Marketed

formulation

(TheoSR) OG10 OG27 FS9

Cmax

(µg/mL) 16.45±1.97 19.24±1.96 20.13±1.50 20.12±2.34

Tmax

(h) 6.0 5.2 5.1 4.2

Ke

(h-1

) 0.06 0.045 0.044 0.099

T1/2

(h) 11.55 15.4 15.75 7.0

AUC0→t

(μg·h/mL) 84.11 70.40 83.75 97.04

AUC0→∞

(μg·h/mL) 289.61 369.06 406.93 198.34

5.2.6 Short term Stability studies of selected formulations

Table 4.44 In vitro dissolution of matrix tablet before and after storage

(stability study of optimized batch OG10)

Time

(h)


Before

storage

After

storage

0 0 0

1 8.84 9.45

2 12.89 14.54

3 21.71 22.12

4 23.53 25.41

5 28.52 30.12

6 37.52 38.45

7 60.82 63.12

8 88.32 90.14

f2 value 84.92

Results



(stability study of optimized batch OG27)

Time

(h)


Before

storage

After

storage

0 0 0

1 4.24 4.81

2 7.15 8.45

3 9.34 9.66

4 11.54 11.24

5 13.21 13.84

6 37.35 38.1

7 57.25 58.14

8 84.25 84.84

f2 value 95.41


(stability study of optimized batch FS9)

Time

(h)


Before

storage

After

storage

0 0 0

1 8.05 7.14

2 9.72 8.94

3 11.41 11.01

4 12.32 13.24

5 13.24 14.15

6 20.49 21.21

7 30.19 32.01

8 62.88 60.14

f2 value 84.83

Results


5.3 Diclofenac sodium

5.3.1 Identification of drug

a) Melting point study

Melting point of Diclofenac sodium was determined by capillary method found

to be 284ºC, which complied with USP standards, indicate purity of the drug.

b) IR spectroscopy study

Figure 2.37 IR spectrum of Diclofenac sodium

The major peaks obtained in the infra red spectrum are shown in Table 4.47.

Table 4.47 Data of IR with vibrations and its frequency

Vibrations Frequency

(cm-1

)

N-H stretching 3430.59

CH2-CH3 deformation 1452.57

CH2-CH3 deformation 1470.11

O-H bending 1387.42

C-Cl stretching 748.12

This is in accordance with standard IR spectrum of Diclofenac sodium.

The IR spectrum of Diclofenac sodium is shown in Figure 2.37.

Results


5.3.2 Preformulation Study by Differential Scanning Calorimetry (DSC)

Drug excipients compatibility study by DSC

Figure 2.38 DSC thermogram of Diclofenac sodium

Figure 2.39 DSC thermogram of prepared core tablet

Results


5.3.3 Method of estimation of drug

a) Determination of λ max of Diclofenac sodium in purified water.

Figure 2.40 Standard curve of Diclofenac sodium in purified water

Results


Table 4.48 Linearity of Diclofenac sodium in different media

Concentration

(μg/mL)

UV Absorbance in different media

Distilled

water

Phosphate

buffer saline

pH 7.4

Phosphate

buffer saline

pH 6.8

2 0.172 0.284 0.245

4 0.221 0.337 0.307

6 0.267 0.364 0.4

8 0.308 0.401 0.466

10 0.344 0.476 0.504

12 0.396 0.569 0.581

14 0.44 0.598 0.69

R square 0.998 0.970 0.988

Slope 0.022 0.027 0.035

Intercept 0.131 0.215 0.172

Figure 2.41 Calibration curve for Diclofenac sodium in distilled water

Results


Figure 2.42 Calibration curve for Diclofenac sodium in phosphate buffer

saline, pH 7.4

Figure 2.43 Calibration curve for Diclofenac sodium in phosphate buffer

saline, pH 6.8

Results


5.3.4 Evaluation of Diclofenac sodium compression coated tablets

Table 4.49 Physicochemical properties of fast disintegrating core tablets

containing various disintegrating agents (C01-C04)

Code

Weight

variation

(%)

Hardness

(Kg/cm2)

Drug

Content

(%)

DT

(sec)

C01 105 ± 3.89 2.1 ± 0.09 97.48 58

C02 105 ± 3.94 2.2 ± 0.08 101.78 110

C03 105 ± 3.31 2.5 ± 0.08 98.45 38

C04 105 ± 3.33 2.1 ± 0.12 100.78 180

DT-Disintegration time

Table 4.50 Physicochemical properties of fast disintegrating core tablet

containing various combinations of MCC with other

disintegrating agents (C05-C13)

Code

Weight

variation

(%)

Hardness

(Kg/cm2)

Drug

content

(%)

DT

(sec)

C05 155 ± 3.45 2.9 ± 0.45 99.47 18

C06 155 ± 3.46 2.1 ± 0.64 98.46 40

C07 155 ± 3.12 3.1 ± 0.34 96.75 MT* 600

C08 155 ± 3.66 2.1 ± 0.34 100.36 110

C09 155 ± 3.11 2.3 ± 0.64 101.3 120

C10 200 ± 3.34 2.2 ± 0.78 97.35 17

C11 200 ± 3.23 3.2 ± 0.34 101.23 180

C12 200 ± 3.13 2.7 ± 0.24 97.45 140

C13 200 ± 3.43 2.1 ± 0.34 100.23 MT* 600

DT-Disintegration time, MT*- More than

Results


Compression Coating of Fast Disintegrating Core Tablets (C05)

Table 4.51 Physical properties of compression coated tablets of OG

prepared by wet granulation method using 5% starch paste

(CC14-CC17)


(mg)

Hardness

(Kg/cm2)

Friability

(%)

Rel5h

(%)

CC14 355 ± 1.24 3.1 ± 0.14 0.89 25.34

CC15 455 ± 1.14 3.3 ± 0.14 0.84 22.34

CC16 555 ± 1.35 3.7 ± 0.16 0.79 18.64

CC17 655 ± 1.21 3.6 ± 0.11 0.66 11.14


Table 4.52 In vitro dissolution study of prepared compression coated

tablets (CC14-CC17)

Time

(h)


CC14 CC15 CC16 CC17

0 0 0 0 0

1 3.14 2.54 0 0

2 5.32 4.33 2.64 0

3 10.22 9.41 6.14 3.14

4 21.21 19.24 14.14 5.46

5 25.34 22.34 18.64 11.14

Figure 2.44 Comparative dissolution profiles of prepared compression

coated tablets (CC14-CC17)

0

10

20

30

0 1 2 3 4 5

CP

R

Time (h)

CC14 CC15 CC16 CC17

Results


Table 4.53 In vitro dissolution study of prepared compression coated tablet

with or without rat caecal content (CC17)

Time

(h)


Without RC With RC

0 0 0

1 0 0

2 0 0

3 3.14 3.14

4 7.14 7.2

5 11.14 11.13

6 22.14 38.24

7 28.34 58.24

8 35.24 84.24

f2 value 26.27

RC-Rat caecal


coated tablet with and without rat caecal content (CC17)

Results


Table 4.54 Physical properties of compression coated tablets containing

various concentrations of OG prepared by wet granulation

method using 4% PVPK30 (CC18-CC21)

Code

Weight

variation

(mg)

Hardness

(Kg/cm2)

Friability

(%)

Rel5h

(%)

CC18 355 ± 1.31 3.1 ± 0.09 0.89 16.24

CC19 455 ± 1.42 3.3 ± 0.16 0.84 12.34

CC20 555 ± 1.25 3.7 ± 0.14 0.79 10.21

CC21 655 ± 1.14 3.6 ± 0.11 0.66 5.14



tablets (CC18-CC21)

Time

(h)


CC18 CC19 CC20 CC21

0 0 0 0 0

1 0 0 0 0

2 3.14 2.34 0 0

3 6.21 5.64 3.41 2.1

4 12.24 10.24 7.61 3.14

5 15.24 12.34 10.21 5.14



Results




Time

(h)


Without RC With RC

0 0 0

1 0 0

2 0 0

3 2.1 2.14

4 3.14 3.2

5 5.14 5.18

6 12.26 34.21

7 18.24 58.24

8 30.24 80.14

f2 value 23.53

RC-Rat caecal

Figure 2.47 Comparative dissolution profile of prepared compression


Results



various concentrations of OG given by wet granulation using

4% PVPK30 (CC22-CC24)


(mg)

Hardness

(Kg/cm2)

Friability

(%)

Rel5h

(%)

CC22 555 ± 1.24 3.1± 0.16 0.89 20.14

CC23 555 ± 1.64 3.3± 0.14 0.84 19.32

CC24 555 ± 1.67 3.7± 0.31 0.79 16.24



tablets (CC22-CC24)

Time

(h)


CC22 CC23 CC24

0 0 0 0

1 0 0 0

2 7.14 6.24 2.34

3 12.24 12.24 9.24

4 17.24 16.16 13.13

5 20.14 19.32 16.24



Results



various concentrations of OG prepared by direct compression

method (CC25-CC28)

Code

Weight

variation

(mg)

Hardness

(Kg/cm2)

Friability

(%)

Rel5h

(%)

CC25 355 ± 1.24 3.1 ± 0.14 0.89 11.14

CC26 455 ± 1.34 3.3 ± 0.11 0.84 11.24

CC27 555 ± 1.11 3.7 ± 0.09 0.79 8.31

CC28 655 ± 1.99 3.6 ± 0.08 0.66 3.11



tablets (CC25-CC28)

Time

(h)


CC25 CC26 CC27 CC28

0 0 0 0 0

1 0 0 0 0

2 2.24 0 0 0

3 5.47 4.24 2.1 0

4 8.84 7.14 4.15 2.22

5 11.14 11.24 8.31 3.11



Results




Time

(h)


Control With RC

0 0 0

1 0 0

2 0 0

3 0 0

4 2.22 2.31

5 3.11 3.16

6 10.34 30.14

7 16.34 55.51

8 27.27 78.24

f2 value 23.65

RC-Rat caecal



Results


Table 4.62 Physical properties of compression coated tablets prepared

using combinations of OG with other polymers by direct

compression method (CC29-CC40)

Code

Weight

variation

(mg)

Hardness

(Kg/cm2)

Friability

(%)

Rel5h

(%)

CC29 455 ± 1.3 4.6± 0.14 0.67 -*

CC30 555 ± 1.6 4.2± 0.14 0.84 36.45

CC31 655 ± 1.4 4.7± 0.26 0.87 30.12

CC32 455 ±1.6 4.6 ± 0.32 0.64 27.34

CC33 555±1.5 4.8 ±0.14 0.34 25.34

CC34 655±1.6 4.8 ± 0.15 0.67 24.15

CC35 455±1.9 4.1 ± 0.14 0.69 -*

CC36 555±1.7 4.6 ± 0.36 0.48 -*

CC37 655±1.8 4.7 ± 0.54 0.84 -*

CC38 455 ± 1.8 3.6 ± 0.64 0.67 20.31

CC39 555 ± 1.6 4.6 ± 0.54 0.78 14.35

CC40 655 ± 1.6 4.5 ± 0.34 0.67 11.64

Rel5h-Drug release after 5h of dissolution

*- Tablets were broken down as soon as they placed in dissolution medium

Results


Formulation of Coat Using Factorial Design for OG and GG


OG and GG given by direct compression for 32 factorial

design (FC1-FC9)

code

Weight

variation

(mg)

Hardness

(Kg/cm2)

Friability

(%)

Drug

content

(%)

Rel5h

(%)

FC1 405 ± 1.25 4.51 ± 0.08 0.45 101.2 32.12

FC2 505 ± 1.25 4.62 ± 0.04 0.65 101.2 18.65

FC3 605 ± 1.91 4.23 ± 0.08 0.64 99.47 14.44

FC4 405 ± 1.16 5.14 ± 0.14 0.48 96.78 26.45

FC5 505 ± 1.64 4.32 ± 0.14 0.57 97.97 21.44

FC6 605 ± 1.82 4.64 ± 0.08 0.67 96.54 8.88

FC7 405 ± 1.33 4.76 ± 0.08 0.55 102.9 16.44

FC8 505 ± 1.66 5.14 ± 0.04 0.59 100.8 10.21

FC9 605 ± 1.78 4.42 ± 0.08 0.77 98.94 5.45



tablets (FC1-FC4)

Time

(h)


FC1 FC2 FC3 FC4

0 0 0 0 0

1 3.9 ± 0.6 3.1 ± 0.2 2.1 ± 0.5 1.5 ± 0.6

2 5.9 ± 1.2 5.4 ± 0.6 4.3 ± 0.8 2.9 ± 0.7

3 15.65 ± 1.8 12.45 ± 0.9 9.64 ± 1.0 8.5 ± 1.1

4 24.31 ± 1.2 15.23 ± 1.2 11.94 ± 1.4 14.55 ± 1.4

5 32.12 ± 1.6 18.65 ± 1.1 14.44 ± 1.9 26.45 ± 1.1

Results



tablets (FC5-FC9)

Time

(h)


FC5 FC6 FC7 FC8 FC9

0 0 0 0 0 0

1 0 0 0 0 0

2 2.1±0.4 0 0 0 0

3 8.1±1.2 4.66±0.8 2.2±0.5 2.2±0.1 2.6 ± 0.2

4 10.78±1.1 6.57±0.6 9.45±0.9 6.0±0.6 3.78±0.3

5 21.44±1.3 8.88±0.9 16.44±1.1 10.21±0.5 5.45±0.5

Figure 2.51 Surface plot for rel5h of prepared compression coated tablets

(FC1-FC9)

Figure 2.52 Comparative dissolution profile of prepared compression

coated tablets (FC1-FC9)

-1

0

-1

0

10

10

20

30

40

Rel5h

OG

GG

0-10 10-20 20-30 30-40

Results



with or without rat caecal content (FC9)

Time

(h)


Without RC With RC

0 0 0

1 0 0

2 0 0

3 2.6 2.4

4 3.78 3.6

5 5.45 5.60

6 12.34 39.32

7 20.31 64.35

8 35.24 97.64

f2 value 19.62

RC-Rat caecal


coated tablet (FC9) with and without rat caecal content

Results


Table 4.67 Release kinetics of prepared compression coated tablets of

Diclofenac sodium (FC9)

Models R Square K Inference

Zero order 0.9874 27.0782 Passes

First order 0.9052 -0.5514 Fails

Matrix 0.9081 40.0562 Fails

Korsmeyer-Peppas 0.9983 20.8684 Passes

Hixon Crowell 0.9394 -0.1398 Fails

Best fit model Korsmeyer-Peppas

Parameters

n 0.756

k 20.8684

5.3.5 Scanning electron microscopy of selected formulation

Figure 2.54 Photographs of surface morphology of compression coated

tablet at time intervals of 0h, 2h, 5h and 6h of dissolution

(FC9)

Results


5.3.6 In vivo pharmacokinetic study of some selected compression coated

formulations of Diclofenac sodium (CC28 and FC9)

Figure 2.55 HPLC chromatogram of rabbit plasma sample spiked with

Diclofenac sodium and naproxen (internal standard)

.

Results


Table 4.68 Calibration curve of Diclofenac sodium in rabbit plasma

Sr. No. Concentration

(g/mL)

Peak area of

Diclofenac

sodium

(mV/sec)

Peak area of

naproxen

(mV/sec)

Peak area ratio of

Diclofenac

sodium/naproxen

1 0.5 69612 1120142 0.062146

2 1 121496 982546 0.123654

3 2.5 238624 971542 0.245614

4 5 547857 1232413 0.44454

5 10 730635 1132546 0.645126

6 20 1117708 1014120 1.102146

7 30 1557893 993624 1.56789

Figure 2.56 Calibration curve of Diclofenac sodium in rabbit plasma

y = 0.0506x + 0.0874

R² = 0.9879

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

0 5 10 15 20 25 30

Pea

k a

rea

ra

tio

s

Concentration (mcg/ml)

Results


Table 4.69 In vivo Pharmacokinetic Study of orally administered

compression coated tablet (CC28) and Voveran (Marketed

formulation) to three rabbits under fasted conditions (n=3)

Time

(h)


(µg/mL)

CC28 Marketed

formulation

0 0 0

1 0 16.22 ± 2.31

2 0 23.64 ± 2.11

3 0 12.32 ± 2.0

4 1.23 ± 0.12 7.45 ± 1.94

5 8.64 ± 1.46 4.31 ± 1.64

6 21.21 ± 2.24 2.64 ± 0.84

8 18.24 ± 1.14 1.24 ± 0.67

AUC

(μg·h/mL) 59.87 69.11

Figure 2.57 Plasma concentration profiles of orally administered

compression coated tablet (CC28) and Voveran (Marketed

formulation) to three rabbits under fasted conditions. Each

value represents mean ± S.D. (n=3)

0

5

10

15

20

25

30

0 2 4 6 8

Co

ncen

tra

tio

n (

mcg

/mL

)

Time (h)

CC28 Marketed formulation

Results


Table 4.70 In vivo Pharmacokinetic Study of orally administered

compression coated tablet (FC9) and Voveran (Marketed

formulation) to three rabbits under fasted conditions (n=3)

Time

(h)


(µg/mL)

FC9 Marketed

formulation

0 0 0

1 0 16.22 ± 2.31

2 0.22±0.01 23.64 ± 2.11

3 0.62±0.03 12.32 ± 2.0

4 1.23±0.12 7.45 ± 1.94

5 14.64± 2.31 4.31 ± 1.64

6 22.31± 2.64 2.64 ± 0.84

8 15.64± 1.12 1.24 ± 0.67

AUC

(μg·h/mL) 65.82 69.11

Figure 2.58 Plasma concentration profiles of orally administered

compression coated tablet (FC9) and Voveran (Marketed

formulation) to three rabbits under fasted conditions. Each

value represents mean ± S.D. (n=3)

Results


Table 4.71 In vivo pharmacokinetic parameters for optimized formulations

Parameters Prepared formulations Marketed

formulation

(Voveran) CC28 FC9

Cmax

(µg/mL) 21.21 ± 2.24 22.31 ± 2.64 23.64 ± 2.11

Tmax

(h) 6.2 6.0 1.9

Ke

(h-1

) 0.11 0.085 0.23

T1/2

(h) 6.3 8.15 3.01

AUC0→t

(μg·h/mL) 59.87 65.82 69.11

AUC0→∞

(μg·h/mL) 225.68 249.82 74.50

5.3.7 Short term stability studies of selected formulations

Table 4.72 In vitro dissolution of compression coated tablets before and

after storage (stability study of optimized batch CC28)

Time

(h)


Before

Storage

After

storage

0 0 0

1 0 0

2 0 0

3 0 0

4 2.61 2.10

5 3.16 3.50

6 30.14 32.11

7 55.51 57.14

8 78.24 80.14

f2 value 56.14

Results


Table 4.73 In vitro dissolution of compression coated tablet before and

after storage (stability study of optimized batch FC9)

Time

(h)


Before

Storage

After

storage

0 0 0

1 0 0

2 0 0

3 1.0 1.2

4 1.6 1.8

5 5.45 6.14

6 39.31 40.31

7 64.35 65.33

8 97.22 98.14

f2 value 93.49

design and characterization of...

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