Characterisation and Application of Grewia Gum in Tabletting

CONTENTS

Page

Title page ... . . . .-. I.

Certification ..- ... . . . ... Dedication ... ... ..I ... Ack nowledgemen t ... -.. . . Abstract ... . ... I..

Contents ... -.. ... ..*

CHAPTER 1

INTRODUCTION . . . . 0 0

1.1 Plant Gums -.. .-. ... 1.2 Sources of Plant Gums . . . ... 1- 3 Classification of Plant Gums *.-

1.4 Extraction and purification of Plant Gums

1.5 Cmposition and Structure of Plant Gums

1.6 Analysis of Plant ems .. . ..-

1.6.1 Qualitative Analysis ... .-.

1.7 Physic-chemical Properties of Plant Gums

1.7.1 Molecular weight . . . m.m

1.7.2 Dilute solution Viscometry .em

1.7.3 Gel Permeation Chromatography ..-

1.7.4 Solubility Characteristics a=m

1.8 Pharmaceutical Applications of Plant Gums

1.9 Sustained Release Dosage Forms ... 1.9.1 Formulation Methods ... ... 1.9.. Matrix Tablets ... . . . *a.

1.9.1.2 Encapsulated Sfow Release Granules . , . I. 9. I. 3 Tabletted Slow Release Granulations

1.9-1.4 Drug Complexes . . . ... .em

1.9.2 Progress In Sustained Release Technology

1.9.2.1 Mucoadhesive Delivery Systems ... 1.20 Pharmaceutical Polymer Films .*.

1.10.1 Physical Properties of Polymer Films

1.10.2 Mechanical Properties of Films ...

i

ii

iii

iv

vi

viii

CHAPTER 2

Page

Water Vapour Permeability of Films 56

~lasticisers Used in Pharmaceutical Films 59

Glass Transitf on Temperature ,of Films 60

Thermal Analysis of Films ... 61

Dissolution and Drug Release From Solid

Dosage Forms . .. ... ... 62

Purpose of Study .., *.. 67

EXPERIMENTAL . . . . . . ... 70

Extraction and Purification of DGz Gum 70

Analysis of DGZ Gum .=- ... 71

Phytochemical tests . . . ... 71

Determination of Monosaccharide Content of

Purified DGZ ... ..* ... 72

Molecular weight Determination of DGZ 73

Elemental Analysis ... ... 75

Quantitative Determination of Lipid Content

Of DGZ 0.. -*- 76

Determination of Protein Content . . . 77

Preparation of boric acid mixed indicator 78

Determination of Nitrogen Content 78

Solubility of DGZ Gum in Water 79

Determi nation of Moisture Content of

Powdered DGZ Gum ... ... 79

Determination of Moisture Sorption 80

Ash Value Determination , . . ... 81

Determination of Bulk and Tapped Densities 81

Determination of Particle Density ... 82

Determination of Browning and Charring

Temperatures . . . ... ... 83

Determination of pH of DGZ Dispersions 83

Investigation of Film Properties . . . 83

Preparation of Films .a- a=. 83

Film Evaluation Tests ... ... 86

Macroscopic and Microscopic Examination of

Films 0. - 0 86

Determination of Film Density ... 86

Determination of Mechanical Properties of

Plasticised and Unplasticised Films 86

Determination of Moisture Sorption of Films 88

Determination of Water Vapour Transmission

of ~lasticised and Unplasticised Films 89

Determination of Solubility of DGZ Films in

Phosphate Buffer pH 7.4 .., ... 90

Acute Toxicity Test of DGZ Gum .. 92

Compatibility Studies of DGz with some Drugs 92

Applications of DGZ in Tablet Technology 93

Evaluation of DGZ Gum as Binder in Sodium

Salicylate Tablets ... ... 93

Preparation of Sodium Salicylate Granules 94

Evaluation of DGZ as Disintegrant ... 96

Preparation of Riboflavin Granules 96

Evaluation of DGZ Gum as Sustained Release

Matrix ... ... ... 98

Preparation of Theophylline Hydrate Granules 98

Preparation of Ch lorphenirarnine Maleate

Granules ... . . . . . 100

Evaluation of Granule Properties . . . 10 2

Size Analysis . . . ... . . 10 2

Granule Friability ... . . . 10 2

Bulk and Tapped Densities . . . 10 3

Flow Rate and A,,gle of Repose ... 103

Moisture Content and Equilibrium Moisture

Content of Granules ..- ... 10 4

Moisture Sorption Characteristics of

Granules ... . .. . . . 104

Preparation of Tablets .. . ... 10 5

Page

CHAPTER 3

Evaluation of Tablet Properties . . . 106

Moisture Uptake by Tablets .*. 107

Weight Uniformity of Tablets .. . 10 7

Tablet Hardness ... ... 108

Tablet Diameter and Thickness ... 108

Tablet Friability . . a,. 108

Disintegration Time of Tablets ... 10 9

Determination of Swelling Characteristics of

DGZ Compacts . . . ... ... 10 9

Preparation of Gum Compacts . . . 109

Dissolution Rate Studies on the Tablets 110

Absolute Drug Content of Tablets . . . 112

Stability Tests on the Tablet Formulations 113

RESULTS AND DISCUSSIONS e.0 om.

Grewia (DGZ) Gum ... ... Physicochemical properties .-.

Phytochemical Analysis ... . . . Monosaccharide Content of DGZ . . Molecular Weight of DGZ . . . ... Moisture Content and Moisture Sorption

Characteristics .. . ... Total Ash Content of DGZ . . . The True, Bulk and Tapped Densities of

DGZ Powder ... ... . . . Hausner' s ~uotient and Carr' s

Compressibility . . . ... Solubility of DGZ ... ... pH of DGZ Aqueous ~ispersions ... Properties of BGZ Films ... ..-

Mechanical Properties of Films ...

xii

Page

The Effect of Plasticisers ... Water Vapour Permeability of DGZ Films

Effect of Plasticisers on Water Vapour

Permeability . . . .om ... Moisture Sorption of DGz Films ... Solubility of DGZ Film in Phosphate Buffer

pH 7.4 m. .*. ... Acu te Tox ici ty - .. . . . Thermal Behaviour of DGZ . a

Compatibility of DGZ with Some Drugs and

Excipients ... a** ... Applications of DGZ in Tablet Technology

The Binding Properties of DGZ ... Densities of Granules . . a me.

Flow Properties -.. ... Granule Friability ... ... Moisture Content of Granules -..

Uniformity of Weight and Drug Contents of

Sodium Salicylate Tablets *..

Tablet Crushing Strength and Binder

Concentration . . . ... . Tablet Tensile Strength and Binding

Concentration . . . ... moo

Tablet Binding Capacity and Binder

Concentration . . . ... ... Tablet Friability and Binder Concentration

Disintegration Time and Binder Concentratio

Dissolution Profile a

physical Properties of RJ 3

Weight and Content Unifor

Hardness and Friability of .Lablets

Disintegration Time of Tablets ... Dissolution Profile ... ...

xiii

3.7.3 Application of DGZ in Sustained Release Page

Formulation . . . ... . I . 216

3.7.3.1 Theophylline Hydrate Tablet Formulations 217

3.7.3.1.1 Densities per cent Compressibility and

Hausner ' s Quotient .. . . . . 217

3.7.3.1.2 Flow Rate and Angle of Repose . . 219

3.7.3.1.3 Granule Friability ... ..- 222

3.7.3.1.4 Moisture Content of Granules . . 224

3.7.3.1.5 - In vitro Properties of Sustained Release

Theophylline Hydrate Tablets . . . 2 26

3.7.3.1.6 Uniformity of Neight and Drug Content 226

3.7.3.1.7 Tablet Crushing Strength and Friability 2 28

3.7.3.1.8 Swelling Behaviour of DGz Matrix ... 228

3.7.3.1.9 Effect of Gum Type and Concentration on the

Release of Theophylline Flydrake . . 232

3.7.3.1.10 Effect of pH of Dissolution Medium on Drug

Re1 ease -.. ..- . 4 . 241

3.7.3.1.11 Release Mechanism of DGZ -.. 242

3.7.3- 2 Chlorpheniramine Maleate Tablet Formulations 243

3.7-3.2.1 Densities and per cent Compressibility 245

3.7.3.2.2 Flow Rate and Angle of Repose . . 248

3.7.3.2.3 Granule Friability .*. ... 250

3.7.3.2.4 In vitro Properties of Sustained Release

Chlorphenirarnine Maleate Tablets . . . 2 50

3.7.3.2.5 Uniformity of Weight and Drug Content 252

3.7.3,2.6 Tablet Crushing Strength and Friability 252

3.7.3.2.7 Effect of Gum Type and Concentration on the

Release of Chlorpheniramine Maleate 25 5

3.7.3.2.8 Effect of pH of Dissolution Medium on Drug

Release ..- ... . . 26 2

3.8 stability Studies ... . . 26 3

CHAPTER * SUHMARY AND CONCLUSION . .. s-0 26 6

REFERENCES I.. 0.- a*. 268

APPENDIX moo -a- orno 288