Physico-Technical and Tableting Properties of Grades of Microcrystalline Cellulose Derived from Sorghum and Andropogon Plants

CONTENTS

Page

Acknowledgement ........................................................................................................... iv

Abstract ................................................................................................................................. vi

List of Tables .................................................................................................................... xiv

List of Figures .................................................................................................................. xvi

CHAPTER 1

1.0 GENERAL INTRODUCTION ............................................................................. 1

1.1 OBJECTIVE .............................................................................. -2

1.2 CELLULOSE ........................................................................................................... 3

1.2.1 Production of a-cellulose from plant sources ......................................................... 4

1.2.2 Modification of Cellulose ....................................................................................... 6

1.2.3 Sourcing for microcrystalline Cellulose ................................................................ 8

1.2.3.1 Sorghum bicolour ........................................................................................ 9

1.2.3.2 Andropogon gayanus ................................................................................ 10

1.3 COMPRESSED TABLETS .................................................................................. 10

Methods of Tableting ............................................................................................ 13

Wet granulation ........................................................................................ 15

Dry granulation ......................................................................................... 15

Direct Compression Tableting .................................................................. 16

DIRECT COMPRESSION EXCIPIENT ............................................................. 18

Classification of Direct Compression Excepients ................................................. 18

Development of Direct Compression Excipient ............................................... 19 !' .I.... : . Microcrystalline Cellulose(MCC) ........... : ......................................................... 21

FACTORS IN FORMULATION DEVELOPMENT .......................................... 25

Compressibility .................................................................................................... 26

Fluidity ................................................................................................................. 28 . . Lubrication .......................... .... ........................................................... 29

PHARMACEUTICAL POWDERS ..................................................................... 30

Particle Size and Size Distribution ........................................................................ 31

Determination of Particle Size ............................................................................. 31

Particle Morphology ............................................................................................... 33

Particle Shape and Surface Area ............................................................................ 35

Derived Properties of powders .............................................................................. 36

1.6.5.1 Porosity ........................... ............................................................... 37

1.6.5.2 Density ....................................................................................................... 38

(i) True density .............................................................................................. 39

(ii) Bulk density ............................................................................................... 39

1.6.6 Flow of Powder ......................... .................................................................. 4 1

1.6.7 Water uptake ...................................................................................................... 43

1.6.7.1 Hydration Capacity ............ .................................................................. 43

1.6.7.2 Contact angle ........................................................................................... 44

1.6.7.3 Equilibrium Moisture Content .................................................................. 45

1.6.8 Swelling ............................................................................................................. 45

1.7 COMPRESSION AND COMPACTION ............................................................ 48

1.7.1 Particle Rearrangement (Transitional Re-Packing) .............................................. 50

1.7.2 Deformation at points of Contact .......................................................................... 51

1.7.3 Fragmentation ......................................................................................................... 52

1.7.4 Plasto-Elasticity and Brittle - Fracture Index ........................................................ 54

1.7.5 Bonding .................................................................................................................. 56

1.7.5.1 Mechanical Bonding ................................................................................. 57

1.7.5.2 Intermolecular Forces of Attraction .......................................................... 58 . . 1.7.5.3 Liquid Surface Film ................................................................................... 58

1.7.5.4 Bonding Propensity ................................................................................... 59

1.7.6 Densification Behaviour of Powders ..................................................................... 59

1.7.6.1 Pressure - Volume Relationship ................................................................ 60

1.7.6.2 Heckel EquationIAnalysis ......................... ............... ................................. 60

1.7.6.3 Kawakitas Equation ............. ............................................................. 65

EVALUATION OF TABLETSTRENGTH ........................................................ 66

Crushing Strength .................................................................................................. 66

Tensile Strength ...................................................................................................... 67

Indentation Hardness ...................... ................................................................ 68

Reworking Potential ..................... .............................................................. 69

Work of Failure ............................. .............................................................. 70 . , .. .-

DIRECT COMPRESSION FORMULATIONS .................................................. 71

Dilution Capacity ................................................................................................... 72

Paracetamol ............................... ...................................................................... 73

Ascorbic acid ............................ .................................................................. 75

Metronidazole ......................................................................................................... 76

CHAPTER 2

2.0 EXPERIMENTAL ................................................................................................. 79

2.1 IDENTIFICATION OF PLANTS .................................................... 79

2.2 MATERIALS ....................................................................................................... 79

2.3 METHODS ............................................................................................................. 80

2.3.1 Preliminary Experiments in the Production of a -Cellulose ............................ .... 80

2.3.1.1 Effect of particle Size Fraction of Standing Material ............................. 80

2.3.1.2 Effect of Reagent type ............................................................................... 81

2.3.1 Control of Processing Conditions .......................................................................... 81

2.3.1.1 Digestion/Delignification .......................................................................... 81

2.3.1.2 Removal of hemicelluloses (Maceration) ................................................. 82

2.3.1.3 Bleaching of a-Cellulose .......................... ......................................... 83

2.3.3 Extraction of a-Cellulose From Sorghum and Andropogon ............................... 84

2.3.4 Production of Microcrystalline Cellulose ......................................................... 85

2.3.5 Physicochemical Properties of SOMCC and AMCC ................................ 86 . . 2.3.6 Acute toxicity test ................................................................................................... 86

2.3.7 Powder properties ................................................................................................... 87

2.3.7.1 Particle Size Distribution .......................................................................... 87

2.3.7.2 Particle morphology .................................................................................. 88

2.3.7.3 Bulk Density .............................................................................................. 88

2.3.7.4 True density ................................... .... ...................................................... 89

2.3.7.5 Porosity, Compressibility Index and Angle Repose ................................ 89

2.3.8 Hydration Capacity ......................................................................................... 90

2.3.9 Swelling Capacity ................................................................................................... ..... ? ......... v2 . 91

2.3.10 Compactability aiia ablet tin^ proberties ........................................................... 92

2.3.10.1 Preliminary Experiment ......................................... .................................. 92

2.3.10.2 Compactability of SOMCC and AMCC ................................................. 95

2.3.1 1 Spectroscopic analysis .......................................................................................... 97

2.3.1 1.1 SOMCC and AMCC ................................................................................ 97

2.3.1 1.2 ~cetamino~hen, .~scorbic.acid, and Metronidazole ................................ 97

2.3.1 1.3 Drug-Excipient compatibility Tests ........................................................ 97

2.3.12 Direct Compression Formulations ...................................................................... 98

2.3.12.1 Preparation of Acetaminophen Tablets ............................ .. ................ 98

2.3.12.2 Preparation of Ascorbic acid Tablets ...................................................... 98

2.3.12.3 Preparation of Metronidazole Tablets ................................................. 100

2.3.1 3 Evaluation of tablet properties ............................................................................. 100

2.3.13.1 Weight Variation .................................................................................. 101

2.3.13.2 Tablet Dimensions and Density .............................................................. 101

2.3.13.3 Tablet Strength ........................................................................................ 102

2.3.14 Reworking potential ......................................................................................... 103

2.3.15 Friability tests ................................................................................................. 103

2.3.16 Disintegration tests ............................................................................................. 104

2.3.17 Dissolution testing ........................................................................................... 104

2.3.18 Effect of storage on drug content ......................................................................... 105

CHAPTER 3

RESULTS AND DISCUSSION ................................................................. 107

IDENTIFICATION OF PLANTS ................................................... 107

EXTRACTION OF a-CELLULOSE ................................................................. 107

Digestion and Delignification ............................................................................. 107

Effect of particle size fractions .......................................................... 107

Effect of Reagent type ......................................................................... 108

Effect of time and temperature ............................................................. 108

Effect of concentration of sodium hydroxide ......................................... 111

Removal of hemicellulose by maceration .......................................................... 111

Bleaching of a-Cellulose ..................................................................................... 112

Effect ofpH ............................................................................................ 114

Extraction of Cellulose from sorghum and Andropogon plants ........................ 114

Processing Conditions ....................................................................................... 114

Yield of cellulose grades ..................................................................................... 116

Physicochemical properties of SC, AC, SOMCC and AMCC ......................... 116

Organoleptic properties ....................................................................................... 116

Compendia1 tests on the cellulose grades ..................................................... 118

Acute Toxicity test ....... :: .~.:':..!:.r ... ....i........ .......................................................... 118

Powder Properties ............................................................................................ 120 ... Particle size and size Distribution ........................................................................ 120

Particle Morphology ............................................................................................. 122

Infrared Spectra of SOMCC and AMCC ....................................................... 122

Densities .............................................; ............................................................ 122 ....... Flowability ......................................................................................................... 128

Hydration Capacity .............................................................................................. 131

Swelling Capacity ................................................................................................ 131

Preliminary evaluation of cellulose grades ........................................................ 135

Effect as filler-binder ..................... .............................................................. 135

Effect as disintegrant ...................................................................................... 138

Compression and Compaction Characteristics of SOMCC and AMCC ........... 141

3.8.1 Effect of particle size on compressibility of the polymers .......... 14 1

3.8.2 Compressibility profiles of SOMCC, AMCC and Avicel PH 10 1 .................... 144

3.8.3 Consolidation behaviours of SOMCC and AMCC ........................................... 146

3.8.4 Reworking potential ........................... .. ........................................................... 151

3.8.5 Dilution Capacity of SOMCC or AMCC ...................... .................................. 153

3.8.5.1 Acetaminophen Compacts .................................................................... 154

3.8.5.2 Ascorbic acid Compacts ................... .. .............................................. 160

3.8.5.3 Metronidazole Compacts ........................................................................ 166

3.9 Drug - Excipient compatibility tests with SOMCC or AMCC .......................... 169

3.10 Formulations ................ .................................................................................. 171

3.10.1 Acetaminophen tablets ......................................................................................... 171

3.10.2 Ascorbic acid tablets ........................... .. ...................................................... 177

3.10.3 Metronidazole tablets ........................................................................................... 179

3.10.4 Uniformity of weight, thickness and diameter .................................................... 188

3.10.5.1 Effect of aging on the drug content ................................................................. 188

CHAPTER 4

4.0 SUMMARY AND CONCLUSION ................................................................... 191

REFERENCES ............................................................................................................. 197

APPENDIX ............................. .................................................................................... 214