FORMULATION AND EVALUATION OF MUCOADHESIVE BUCCAL

TABLETS OF SERTACONAZOLE NITRATE FOR TOPICAL DRUG

DELIVERY

Thesis

Submitted to the Faculty of Pharmaceutical Sciences

Pt. B. D. Sharma University of Health Sciences

(Govt. of Haryana) Rohtak- 124001

for the award of the degree of

MASTER OF PHARMACY

(PHARMACEUTICS)

By

Shikha Bhardwaj

PDM College of Pharmacy

Sector 3A, Sarai Aurangabad, Bahadurgarh, Haryana 124507

2013-2015

Registration No. 13-PDM-282 Roll No. 190642

 CERTIFICATE

The work embodied in the thesis entitled Formulation and Evaluation of Mucoadhesive
Buccal Tablets of Sertaconazole nitrate for Topical Drug Delivery is based on my own
research work and carried out under the supervision of Dr. Hema Chaudhary, Principal and
HOD (Department of Pharmaceutics) PDM College of Pharmacy during 2014-2015.

The present work has not been submitted in part or full for any degree or diploma of this or
any other university.

Place : Bahadurgarh Candidate

Date :

Supervisor

Dr. Hema Chaudhary

HOD, Department of Pharmaceutics

Forwarded By

Dr. Hema Chaudhary

Principal

PDM College of Pharmacy

Head

Department of Pharmacy

Pt. B.D. Sharma University of Health Sciences (Govt. of Haryana)

Rohtak - 124001

Haryana, India
 DECLARATION

I hereby declared that this dissertation entitled Formulation and Evaluation of

mucoadhesive buccal tablets of Sertaconazole nitrate for topical drug delivery has been
planned and carried out by me under the supervision of Dr. Hema Chaudhary at Department
of Pharmaceutics, PDM College of Pharmacy, Bahadurgarh.

It is also stated that no part of this work has been submitted either in part or in full for any
other degree of PDM College of Pharmacy or any other college/university and that all the
sources I have used or quoted have been indicated and acknowledged by complete reference.

Date: Shikha Bhardwaj

Place: Bahadurgarh Department of Pharmaceutics

PDM College of Pharmacy

Bahadurgarh
 CERTIFICATE OF AUTHENTICITY

Name of candidate : Shikha Bhardwaj

Fathers name : Mr. Rajender Sharma

Roll no. : 190642

Class : M.Pharma 2nd year (Pharmaceutics)

Topic entitled : Formulation and Evaluation of mucoadhesive buccal

tablets of Sertaconazole nitrate for topical drug

delivery

Name of supervisor (s) : Dr. Hema Chaudhary

Name of institution : PDM College of Pharmacy

It is certified that nothing contained in thesis has been plagiarized from any source and no
false data have been included in the thesis. I understand that if wrong information is
furnished, action may be taken against me as per law.

Supervisor Principal
 CONTENTS

S.NO TITLE PAGE

NO.

Certificate Ii
Acknowledgement Iii
iv
Declaration

Certificate of authenticity v

CHAPTER 1 INTRODUCTION

1.0 Introduction 1
1.1 Different routes of drug administration 1
1.1.1 Local route 1
1.1.1.1 Topical route 1
1.1.1.2 Deeper tissues 1
1.1.1.3 Arterial supply 1
1.1.2 Systemic route 2
1.1.2.1 Oral route 2
1.1.2.2 Sublingual or buccal route 2
1.1.2.3 Rectal route 2
1.1.2.4 Cutaneous 2
1.1.2.5 Inhalation 2
1.1.2.6 Nasal 2
1.1.3 Parenteral 3
1.2 Morphology of oral cavity 4
1.2.1 Oral mucosa 5
1.2.1.1 Mucus layer 6
1.2.1.1.1 Composition of mucus 7
1.2.1.1.2 Function of mucus layer 8
1.2.1.2 Salivary secretion 8
1.2.1.2.1 Functions of saliva 8
1.2.1.2.2 Composition of saliva 9
1.3 Factors influencing drug absorption from the oral cavity 9
1.3.1 Permeability of oral mucosa to the drug 9
1.3.2 Physiochemical characteristic of the drug 10
1.3.2.1 Molecular weight 10
1.3.2.2 Degree of ionization 10
1.3.2.3 Lipid solubility 10
1.3.2.4 pH of saliva 10
1.4 Mucoadhesion 10
1.4.1 Mechanism of Mucoadhesion 11
1.4.2 Theories of Mucoadhesion 12
1.4.3 Factors affecting Mucoadhesion 14
1.5 Significance of Mucoadhesive drug delivery system 16
1.6 Bioadhesive and mucoadhesive polymers 16-17
1.6.1 Classification of Mucoadhesive polymers 17-18
1.7 Formulation 19
1.7.1 Buccal dosage form 19
1.7.1.1 Buccal tablet 19
1.7.1.2 Buccal gel and ointment 20
1.8 Profile of Sertaconazole nitrate 21
1.9 Solid dispersion 21
1.9.1 Historical background 21
1.9.2 Definition of solid dispersion 21
1.9.3 Ideal candidate for solid dispersion 22
1.10 Techniques for Dissolution enhancement 22-24
1.11 Advantages of Solid dispersion 25
1.12 Disadvantages of Solid dispersion 25
1.13 Applications of Solid dispersion 25

CHAPTER 2 LITERATURE REVIEW

2.0 Literature Survey on Mucoadhesive Buccal table 26-30

2.1 Drug Profile 31
2.1.1 Sertaconazole nitrate 31
2.1.1.1 Chemical structure 31
2.1.1.2 Chemistry 31
2.1.1.3 Mode of action 32
2.1.1.4 Pharmacodynamics/kinetics 32
2.2 Polymer profile 33
2.2.1 Carbopol 934P 33
2.2.2 Sodium carboxymethyl cellulose 34-35
2.2.3 Hydroxy Propyl Methyl Cellulose 35-36
2.2.4 Sodium alginate 36
2.3 Excipients profile 37
2.3.1 Magnesium Stearate 37
2.3.2 Mannitol 38

CHAPTER 3 WORK ENVISAGED

3.0 Aim of Proposed Research Work 39

3.1 Objectives of Proposed Research Work 39
3.2 Selection of Drug Substance 39
3.3 Selection of Route of administration 40
3.4 Rationale of Study 40
3.5 Methodology 40-42
 CHAPTER 4 MATERIALS AND METHODS

4.0 Materials and Methods 43

4.1 List of Equipments 43
4.2 Chemicals Used in the Study 44

CHAPTER 5 EXPERIMENTAL WORK

5.0 Experimental Work 45

5.1 Characterization of Drug 45
5.2 Identification of Drug 45
5.2.1 Determination of Melting Point 45
5.2.2 Determination of Partition coefficient 45
5.2.3 Differential Scanning Colorimetry 46
5.2.4 Fourier Transform Infrared (FT-IR) Analysis 46
5.2.5 Solubility studies of drug 46
5.2.6 UV Spectra of Sertaconazole nitrate 47
5.3.7 Moisture content 47
5.3 Analytical methodology 47
5.3.1 Preparation of Standard Calibration Curve of drug by UV 47
Spectrophotometer
5.4 Preformulation Studies 47
5.4.1 Angle of Repose 47
5.4.2 Bulk Density 48
5.4.3 Tapped Density 48
5.4.4 Hausners Ratio 49
5.4.5 Carrs Index 49
5.4.6 Drug-excipients compatibility studies 50
5.4.6.1 Physical compatibility study 51
5.4.6.2 Physicochemical compatibility study 51
5.4.6.2.1 FT-IR (Fourier Transform Infrared Analysis) 51
5.5 Formulation of Solid Dispersion 51
5.5.1 Method of preparation of Solid Dispersion 51
5.6 Evaluation of Solid dispersion of drug formulation 51
5.6.1 Solubility Studies 52
5.6.2 In-vitro Dissolution Studies 53
5.6.3 DSC Thermogram 53
5.7 Formulation of Sertaconazole nitrate Mucoadhesive Buccal 53
tablets (200 mg)
5.8 Evaluation and Optimization of Mucoadhesive Buccal tablets 54
of tablets
5.8.1 Micromeritic properties of the formulation 54
5.8.2 Thickness 54
5.8.3 Hardness 54
5.8.4 Friability 55
5.8.5 Uniformity of weight 55
5.8.6 Determination of Drug Content 56
5.8.7 Surface pH 56
5.8.8 Preparation of Buccal Mucosa 56
5.8.8.1 Ex-vivo Mucoadhesion strength 56
5.8.8.2 Ex-vivo Mucoadhesion time 57
5.8.9 Swelling studies 57
5.8.10 In-vitro dissolution studies 57
5.8.11 Ex-vivo diffusion studies 58
5.9 Antifungal activity using cup plate method 59
5.10 Release kinetics and Mechanism of In-vitro drug release of 59
the optimized formulation
5.10.1 Kinetics of Drug release 59
5.10.2 Mechanism of Drug release 59
5.11 Accelerated stability studies as per ICH guidelines 62

CHAPTER 6 - RESULTS AND DISCUSSION

6.0 Results and discussion 63

6.1 Characterization of drug 63
6.1.1 Physical description and Organoleptic properties 63
6.2 Identification of drug 63
6.2.1 Melting Point 63
6.2.2 Partition coefficient 63
6.2.3 DSC Thermogram 64
6.2.4 Fourier Transform Infrared (FT-IR) Analysis 64
6.2.5 Solubility studies 66
6.2.6 UV Spectroscopic Analysis 67
6.2.7 Moisture Content 67
6.3 Analytical Methodology 68
6.3.1 Preparation of standard calibration curve of drug using UV 68
spectrophotometer
6.4.1 Powder Flow Property of Pure Drug 69
6.4.1.1 Angle of Repose 70
6.4.1.2 Bulk Density 70
6.4.1.3 Tapped density 70
6.4.1.4 Hausners Ratio 70
6.4.1.5 Carrs index 70
6.4.1.6 Drug excipient compatibility studies 71
a) Physical compatibility study 71
b) Chemical compatibility study 72
6.5 Preparation of solid dispersion of sertaconazole nitrate 73
6.5.1 Evaluation of prepared solid dispersion 73
6.5.1.1 Micromeritic properties of solid dispersion formulation 73
6.5.1.2 Solubility study 74
6.5.1.3 In-vitro dissolution of prepared formulations 74
6.6 Formulation of sertaconazole nitrate mucoadhesive buccal 76
 tablets
6.7 Evaluation of mucoadhesive buccal tablets 77
6.7.1 Micromeritic properties of prepared formulations 77
6.7.2 Thickness 79
6.7.3 Hardness 79
6.7.4 Friability 80
6.7.5 Weight variation 81
6.7.6 Determination of drug content 82
6.7.7 Surface pH 83
6.7.8 Ex- vivo mucoadhesion strength 84
6.7.9 Ex- vivo mucoadhesion time 86
6.7.10 Swelling studies 88
6.7.11 In-vitro dissolution study 90
6.8 Ex-vivo diffusion studies 92
6.9 Microbiological evaluation of optimized formulation 94
6.10 Release kinetics and mechanism of In-vitro drug release of 95
optimized formulation
6.10.1 Kinetics of drug release 97
6.10.2 Mechanism of drug release 97
6.11 Accelerated stability study for optimized mucoadhesive tablet 97
CHAPTER 7 - SUMMARY 99-101

CHAPER 8 CONCLUSION 102

CHAPTER 9 REFERENCES 103-110

 LIST OF TABLES

Table No. TITLE Page no.

1.1 Composition of Mucus 8
1.2 Mucoadhesive polymers with their Mucoadhesive property 18
1.3 Advantages and Limitations of Buccal drug delivery system 20
2.1 General description of Carbopol 33
2.2 General description of Sodium Carboxy methyl cellulose 34
2.3 General description of Hydroxypropyl methyl cellulose 35
2.4 General description of Sodium Alginate 36
2.5 Profile of Ethyl Cellulose 37
2.6 Profile of Magnesium Stearate 38
2.7 Profile of Mannitol 39
4.1 List of Equipments 44
4.2 List of Chemicals along with their sources 45
5.1 Interpretation of Flow properties of the powder 50
5.2 Method of preparation of Solid dispersion 51
5.3 List of ingredients used in the formula 53
5.4 Weight variation tolerances for uncoated tablets 54
5.5 Interpretation of drug release mechanism by Korsmeyer- 58
peppas model
5.6 Description of kinetic models 59
6.1 Organoleptic properties of drug
6.2 Values of FTIR spectra of the drug
6.3 Quantitative saturation solubility data of Sertaconazole nitrate
6.4 Standard Calibration curve of Sertaconazole nitrate
6.5 Parameters of Standard calibration curve
6.6 Physical characterization as per ICH guidelines
6.7 Solubility profile of pure drug and Solid dispersion
Formulations
6.8 In vitro drug release of Solid dispersion formulations
6.9 Micromeritic properties of Formulations,F1-F9
6.10 Thickness of Formulations, F1-F9
6.11 Hardness of Formulation, F1-F9
6.12 Percentage Friability of Formulations, F1-F9
6.13 Weight variation of Formulations, F1-F9
6.14 Drug Content of Tablet Formulations, F1- F9
6.15 Surface pH of Formulations, F1-F9
6.16 Mucoadhesion strength of Formulations, F1-F9
6.17 Mucoadhesion time of Formulations, F1-F9
6.18 Swelling study of Formulations, F1-F9
6.19 Result of Cumulative percentage drug release of formulation F1
(HPMC), F2, F3 (HPMC: Sodium CMC), F4 (Sodium CMC),
F5 (Carbopol), F6, F7, F8 (Carbopol: Sod.CMC) and
F9(Drug:polymers)

6.20 Ex-vivo diffusion studies (Drug solution)

6.21 Ex-vivo diffusion studies (Tablet)
6.22 Microbiological evaluation of Optimized formulation
6.23 Mathematical analysis of data for Kinetic modeling
6.24 Regression analysis of Kinetic model
6.25 Accelerated stability study for Optimized Mucoadhesive
Buccal tablet

LIST OF FIGURES
Table no. Title Page no.
1.1 Classification of Different route of drug administration 3
1.2 Oral cavity 4
1.3 Structure of Buccal mucosa 6
1.4 Structure of Mucus membrane 7
1.5 Mechanism of Mucoadhesion 12
1.6 Wetting theory of Mucoadhesion 13
1.7 diffusion theory of Mucoadhesion 13
1.8 Fracture theory of Adhesion 14
6.1 DSC of Sertaconazole nitrate
6.2 FTIR spectra of Sertaconazole nitrate
6.3 Saturation solubility data of Sertaconazole nitrate in different
solvents
6.4 Absorption spectra of Sertaconazole nitrate in phosphate buffer
pH 6.8
6.5 Standard Calibration curve of Sertaconazole nitrate
6.6 FTIR Spectra of Drug alone, A. Drug: SCMC, B. Drug:
Carbopol, C. Drug : Sodium Alginate, D. Drug: HPMC
6.7 DSC of Solid dispersion
6.8 Mucoadhesive strength
6.9 Mucoadhesive time
6.10 Swelling study of Mucoadhesive Buccal tablets
6.11 Swelling study of Mucoadhesive tablets
6.12 Cumulative drug release Vs Time of formulations F1 (HPMC),
F2, F3 (HPMC:Sod.CMC), F4 (Sod.CMC),F5 (Carbopol),
F6,F7, F8 (Carbopol: Sod.CMC) and F9 (drug: Carbopol,
SCMC, HPMC)
6.13 In-vitro diffusion study using Franz diffusion cell
6.14 Ex-vivo diffusion studies
6.15 a) Antifungal study of optimized tablet formulation. And b) In-
vitro antifungal study of commercial cream.
6.17 Results of Accelerated stability study of Optimized formulation

LIST OF ABBREVATIONS

Abbrevations Full Form

Alpha
Beta
Gamma
max Absorption Maxima
UV Ultra violet
Nm Nanometer
g Microgram
% Percentage
ml Milliliter
g/ml Microgram per milliliter
hrs Hours
L Liter
G Gram
R2 Regression coefficient
0
C Degree Celcius
w/v Weight by Volume
rpm Rotation per minute
min Minute
LOD Loss on drying
KBr Potassium bromide
BCS Biopharmaceutical Classification system
FTIR Fourier Transform Infrared Spectroscopy
IR Infra-Red
RH Relative Humidity
DSC Differential Scanning Colorimetry