TABLE OF CONTENTS

Chapter-1. Introduction..................................................................................................1-45
1.1 COLON DRUG DELIVERY..........................................................................................................................1
1.2 ANATOMY AND PHYSIOLOGY OF COLON................................................................................................2
1.3 BARRIER TO COLONIC DRUG ABSORPTION.............................................................................................5
1.4 FACTORS GOVERNING COLONIC DRUG DELIVERY..................................................................................6
1.4.1 Transit through GIT.............................................. ....................................................................6
1.4.2 Gastric emptying......................................................................................................................7
1.4.3 Stomach and Intestinal pH.......................................................................................................7
1.4.4 Colonic Microflora....................................................................................................................7
1.5 GASTROINTESTINAL DISEASE STATE.......................................................................................................9
1.6 COLONIC ABSORPTION...........................................................................................................................9
1.7 FACTORS INFLUENCING COLONIC DRUG ABSORPTION........................................................................10
1.8 ENHANCER OF COLONIC DRUG ABSORPTION.......................................................................................11
1.9 DRUG CANDIDATES FOR COLON DELIVERY...........................................................................................12
1.10 APPAROACHES FOR COLONSPECIFIC DRUG DELIVERY........................................................................13
1.11 NEWLY DEVELOPED COLONSPECIFIC DRUG DELIVERY SYSTEMS........................................................14
1.11.1 Intestinal Pressure Controlled Colon Delivery Capsules (PCDCs).........................................14
1.11.2 CODESTH Technology...........................................................................................................14
1.11.3 Colonic Drug Delivery Based on Pectin and Galactomannan Coating..................................15
1.11.4 Azo Hydrogels.......................................................................................................................15
1.12 MICROSPHERES FOR SITESPECIFIC DRUG DELIVERY...........................................................................16
1.12.1 Characteristics of microsphere............................................................................................18
1.12.2 Types of microspheres.........................................................................................................20
1.12.3 Material used for preparation of microspheres...................................................................23
1.12.4 Pharmaceutical applications of microspheres in drug delivery System...............................24
1.12.5 Advantages and Limitation of microspheres........................................................................27
 1.12.6 Limitation.............................................................................................................................27
1.13 PECTIN FOR COLON DRUG DELIVERY..................................................................................................28
1.13.1 Chemistry of pectin..............................................................................................................28
1.13.2 Chemical structure...............................................................................................................30
1.13.3 Degree of esterification........................................................................................................31
1.13.4 General properties of pectin................................................................................................32
1.13.5 Gel formation properties of pectin.......................................................................................34
1.13.6 Pharmaceutical uses of pectin..............................................................................................37
1.14 REVIEW OF LITERATURE......................................................................................................................43
1.16 RESEARCH ENVISAGED........................................................................................................................44
1.17 PLAN OF WORK...................................................................................................................................45

Chapter-2. Drug profile...................................................................................................46-51

2.1 DRUG PROFILE......................................................................................................................................46
2.2 ACTION AND USES................................................................................................................................47
2.2.1 Pharmacological Actions........................................................................................................48
2.2.2 Therapeutic Uses....................................................................................................................48
2.2.3 Oncologic uses........................................................................................................................48
2.2.4 Obstetrics uses.......................................................................................................................49
2.2.5 High altitude illnesses.............................................................................................................49
2.2.6 Endocrine................................................................................................................................49
2.2.7 Diagnostic uses.......................................................................................................................49
2.3 SIDE EFFECTS.........................................................................................................................................50

Chapter-3. Preformulation studies..............................................................52-60

3.1 Physical analysis of Dexamethasone.....................................................................................................52
3.1.1 Physical appearance...............................................................................................................52
3.1.2 Melting Point..........................................................................................................................52
3.1.3 Solubility.................................................................................................................................53
3.2 Identification of drug............................................................................................................................53
3.2.1 Determination of λmax and UV spectrum..............................................................................53
3.2.2 FTIR spectroscopy...................................................................................................................54
3.3 Partition coefficient..............................................................................................................................55
3.4 Calibration curve of Dexamethasone...................................................................................................56
3.5 COMPATIBILITY STUDIES......................................................................................................................58
3.6 RESULTS AND DISCUSSION...................................................................................................................59

Chapter-4. Optimization and Characterization........................61-73

4.1 PREPARATION OF MICROSPHERES.......................................................................................................61
4.1.1 Material................................................................................................................................61
4.1.2 Method of Preparation.........................................................................................................62
4.2 OPTIMIZATION OF MICROSPHERES......................................................................................................62
4.2.1 Optimization of formulation variables..................................................................................62
4.2.2 Optimization of process variables.........................................................................................63
4.2.3 Optimization of stirring speed..............................................................................................63
4.2.4 Optimization of stirring time................................................................................................63
4.3 PREPARATION OF EUDRAGIT COATED PECTIN MICROSPHERES...........................................................68
4.4 CHARACTERIZATION OF MICROSPHERES..............................................................................................68
4.4.1 Shape and Surface Morphology............................................................................................68
4.4.2 Particle size...........................................................................................................................69
4.4.3 Entrapment efficiency (EE)...................................................................................................69
4.4.4 In vitro Drug Release............................................................................................................70
4.5 RESULT AND DISCUSSION.....................................................................................................................72

Chapter-5. Summary and conclusion........................................................73-77

5.1 SUMMARY............................................................................................................................................73
5.2 CONCLUSION........................................................................................................................................77

References..........................................................................................................................78-86
 List of Figures

Figure No. Description Page No.

1.1 Anatomy of colon 4
Structure of pectin (a) A repeating segment of pectin molecule and functional
1.2 30
groups (b) carboxyl (c) ester d) amide in pectin chain
3.1 UV scanning of Dexamethasone in Water 54
3.2 FTIR spectrum of Dexamethasone 55
Calibration curve of Dexamethasone in simulated intestinal fluid (PBS) pH 7.4 at
3.3 57
λmax 241.0 nm
Calibration curve of Dexamethasone in simulated gastric fluid (HCl) pH 1.2 at
3.4 57
λmax 250.2 nm
Calibration curve of Dexamethasone in simulated gastric and intestinal fluid
3.5 58
(acetate buffer) pH 4.5 at λmax 242.6 nm
Calibration curve of Dexamethasone in simulated intestinal fluid (Phosphate
3.6 58
buffer) pH 6.5 at λmax = 245 nm
Calibration curve of Dexamethasone in simulated intestinal fluid (Phosphate
4.1 65
buffer) pH 6.5 at λmax = 245 nm
Optimization of drug concentration for preparation of microspheres in terms of
4.2 65
particle size and drug encapsulation efficiency
Optimization of emulsifier concentration for preparation of microspheres in
4.3 66
terms of particle size and drug encapsulation efficiency
Optimization of stirring speed for preparation of microspheres in terms of
4.4 66
particle size and drug encapsulation efficiency
Optimization of stirring time for preparation of microspheres in terms of particle
4.5 67
size and drug encapsulation efficiency
4.6 SEM photograph of Microspheres 69
In‐ vitro drug release of Dexamethasone in SGF (pH 1.2), SGF & SIF (pH 4.5), SIF
4.7 71
(pH 6.5) and SCF (pH 7.4)
 List of Tables

Table No. Description Page No.

Properties of Human GIT and Metabolic and enzymatic Reactions by Human
1.1 3
GIT Microflora
GIT diseases, which affect the performance of colon‐specific drug delivery
1.2 9
systems
1.3 Various Peptide and Non peptide Drug candidate for colonic delivery system 13
1.4 Microsphere properties 20
1.5 Colon‐specific drug delivery using pectin 41
1.6 Controlled release formulation using pectin 42
3.1 Solubility profile of Dexamethasone. 53
3.2 Assignment of peak of IR spectrum of Dexamethasone 55
3.3 Partition coefficient of Dexamethasone 56
3.4 Drug compatibility studies with the selected excipients 59
4.1 Optimization of variables 64
4.2 Optimized Parameters for the Microspheres formulation 67
4.3 Particle size and entrapment efficiency of Microspheres formulations 69
In‐ vitro drug release of Dexamethasone in SGF (pH 1.2), SGF & SIF (pH 4.5),
4.4 71
SIF (pH 6.5) and SCF (pH 7.4) at different time
 LIST OF ABBREVIATIONS

EE - Entrapment Efficiency

mg - Milligram

mcg - Microgram

ml - Milliliter

λmax - Maximum absorbance

°C - Degree centigrade

µg - Micrograms

FT-IR - Fourier Transformed-Infrared Spectroscopy

Hrs - Hours

PBS - Phosphate Buffer Saline

SEM - Scanning electron Microscope

min - Minutes

t1/2 - Elimination half life

UV - Ultra violet

GIT - Gastro intestinal tract

SIF - Simulated intestinal fluid

SGF - Simulated gastric fluid

SCF - Simulated colonic fluid

Viz. - Videlicet