LARIBA LETICIA 20th

123 Pages·2016·2.14 MB·English

by  Daniel Amissah

KWAME NKRUMAH UNIVERSITY OF SCIENCE AND
TECHNOLOGY
FACULTY OF PHARMACY AND PHARMACEUTICAL SCIENCES
DEPARTMENT OF PHARMACEUTICS

PHARMACEUTICAL EQUIVALENCE STUDIES ON SOME LOCALLY
MANUFACTURED BRANDS OF PARACETAMOL SOLD IN KUMASI

A THESIS SUBMITTED TO THE SCHOOL OF GRADUATE STUDIES IN
PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE
OF MASTER OF SCIENCE IN PHARMACEUTICAL TECHNOLOGY

BY
LARIBA LETICIA

AUGUST, 2016
DECLARATION
“I, Lariba Leticia, declare that I have fully undertaken the study reported herein under
the supervision of Dr. Noble Kuntworbe and that except portions where references
have been duly cited, this dissertation is the result of my research”.

LARIBA LETICIA ………………….. .…...……………
(PG 2351314) (Signature) (Date)

Certified by
DR.NOBLE KUNTWORBE …………............... .…...……………
(Supervisor) (Signature) (Date)

Certified by
PROF. MARCEL T. BAYOR ………………….. …….…………..
(Head of Department) (Signature) (Date)

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DEDICATION
This work is dedicated to my dear husband Barnabas Duut and my lovely children,
Nathaniel, Yenuma and Nyanuo for their sacrifice, love, prayer and support
throughout this period.

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ACKNOWLEDGEMENT
I give thanks to God Almighty who has brought me this far and will still see me
through.
Special thanks and gratitude goes to Dr. Noble Kuntworbe, my supervisor, for his
advice and help while undertaking this project.
A heartfelt gratitude to the management and staff of Pokupharma Limited, most
especially Mr Stephen Danso, Mr Clement Berkoh Gyamfi and Mr Maxwell Nimo
Tetteh for giving me the opportunity to have my industrial attachment with them and
also allowed me to use their quality control laboratories for my research .I will also
like to thank Mr Agyenim Boateng and Anthony Asamoah of Salom Pharmaceutical
Limited.
I am also grateful to Dr. (Mrs) Yaa Asantewaa Osei and all the staff of Komfo
Anokye Teaching Hospital (KATH) manufacturing unit.
I wish to thank my dear husband and mum who have shown me love, care, support
and encouragement. I will forever be grateful.
Lastly, I am grateful to all those who helped me in diverse ways to make this project
work a success. God richly bless you all.

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ABSTRACT
Paracetamol (acetaminophen), N-(4-Hydroxyphenil)-acetamide an over-the-counter
analgesic, antipyretic and anti-inflammatory drug is a widely used drug. There are
numerous generics of Paracetamol tablets available within the health delivery system
in Ghana and globally. This study sought to determine the pharmaceutical
equivalences between some selected brands of Paracetamol produced locally and
compared to one imported brand from England. Thirteen brands of Paracetamol
tablets plus one imported brand (M&A Pharmachem, England) were purchased from
licensed pharmacies within Kumasi. Samples were all immediate-release
conventional, oral dosage forms and were coded to avoid bias. Pharmacopoeial and
non-pharmacopoeial tests such as friability, thickness, hardness, uniformity of
diameter, uniformity of weight, disintegration time, in vitro dissolution testing and
assay were used to assess the pharmaceutical equivalence of the various brands of
Paracetamol tablets. The paddle method was used for the dissolution testing. UV
spectroscopy was used for the assay analysis of all the brands of Paracetamol tablets
sampled. All brands complied with the official specifications for identification,
diameter, thickness and hardness. PLE, PMA, PPH, and POC passed all the test
conducted on it. However brands PSA, PTA and PDA passed majority of the tests and
failed the test for assay. Brands PAS, PMG, and PAN failed the dissolution rate test
and assay. Brand PKI also failed the test for disintegration and dissolution. PAE failed
the weight uniformity test but passed the other tests. PAR performed poorly by failing
the test for friability, weight uniformity and assay. Statistically all brands are different
from the standard in at least one test. Only Brands PLE, PPH and POC are
pharmaceutically equivalent to the standard (PMA) and may be used as alternatives if
they proved to be bioequivalent.
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TABLE OF CONTENTS
DECLARATION.......................................................................................................... i
DEDICATION............................................................................................................. ii
ACKNOWLEDGEMENT ......................................................................................... iii
ABSTRACT ................................................................................................................ iv
TABLE OF CONTENTS ............................................................................................v
LIST OF TABLES ..................................................................................................... ix
LIST OF FIGURES .................................................................................................. xii
ABBREVIATIONS .................................................................................................. xiii
CHAPTER ONE ..........................................................................................................1
1.1 Introduction .............................................................................................................. 1
1.2 Problem Statement ................................................................................................... 3
1.3 Justification .............................................................................................................. 4
1.4 General Objective .................................................................................................... 4
1.5 Specific Objective .................................................................................................... 5
CHAPTER TWO .........................................................................................................6
LITERATURE REVIEW ...........................................................................................6
2.1 Pharmaceutical Equivalence .................................................................................... 6
2.2 Generic Pharmaceutical Products ............................................................................ 7
2.3 Substandard and Counterfeit Medicines .................................................................. 8
2.3.1 Drug Counterfeiting ..............................................................................................9
2.3.2 Data Available on Counterfeit and Substandard Drugs ......................................10
2.3.3 Substandard Drugs in Developing Countries ......................................................11
2.3.4 Causes of Drug Counterfeiting ...........................................................................13
2.3.5 Implications of Counterfeiting Globally .............................................................14
2.3.6 Tackling Substandard and Counterfeit Medicines ..............................................15
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2.3.7 Quantitative and Qualitative Analytical Methods for the Detection of
Counterfeit Medicines ......................................................................................17
2.4 Non-compendial and Compendial Quality Tests on Tablets ................................. 17
2.4.1 Identification .......................................................................................................18
2.4.1.1. Physical Specifications of Tablets ...................................................... 18
2.4.2 UV Visible Spectrophotometric Analysis ...........................................................20
2.4.3 Uniformity of Weight ..........................................................................................21
2.4.4 Content Uniformity .............................................................................................22
2.4.5 Hardness & Friability ..........................................................................................22
2.4.6 Disintegration Test ..............................................................................................24
2.4.7 Dissolution and Disintegration ............................................................................25
2.4.8 Tablet thickness and Diameter ............................................................................25
2.5 Paracetamol (Acetaminophen) ............................................................................... 26
CHAPTER THREE ...................................................................................................28
MATERIALS, EQUIPMENT AND METHODOLOGY .......................................28
3.1 Chemicals and Reagents ........................................................................................ 28
3.2 Equipment and Apparatus ...................................................................................... 28
3.3 Methodology .......................................................................................................... 30
3.3.1 Sampling of Paracetamol Brands from the Market .............................................30
3.3.2 Subjective Physical Assessment of Tablets ........................................................30
3.3.3 Melting Point Determination ..............................................................................30
3.3.4 Identification of Paracetamol using Fourier Transmittance Infrared Spectroscopy
(FTIR) ..............................................................................................................31
3.3.5 Weight Uniformity ..............................................................................................31
3.3.6 Uniformity of thickness of the Paracetamol Tablets ...........................................31
3.3.7 Uniformity of diameter of the Paracetamol Tablets ............................................32
3.3.8 Crushing Strength (Tablet hardness) ...................................................................32
3.3.9 Tablet Friability ...................................................................................................32
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3.3.10 Disintegrations ..................................................................................................32
3.4 ASSAY (UV) ......................................................................................................... 33
3.4.1 Calibration Curve of the UV Spectrophotometer ...............................................33
3.4.2 Determination of Drug Content (ASSAY) ..........................................................33
3.5 In vitro Drug Release (Dissolution Test) for the Paracetamol Tablets .................. 34
3.5.1 Calibration Curve ................................................................................................34
3.5.2 In vitro Drug Release (Dissolution Test) ............................................................34
3.6 ANOVA-based Method Analysis .......................................................................... 35
CHAPTER FOUR ......................................................................................................36
RESULTS ...................................................................................................................36
4.1 Identification Test .................................................................................................. 36
4.1.2 The Melting Point ...............................................................................................36
4.2 Tablet Thickness .................................................................................................... 36
4.3 Tablet Diameter ..................................................................................................... 37
4.4. Weight Uniformity Test ........................................................................................ 38
4.5. Friability Test ........................................................................................................ 39
4.6. Crushing Strength (Hardness) ............................................................................... 40
4.7. Crushing Strength Friability Ratio (CSFR) .......................................................... 41
4.8 Disintegration Test ................................................................................................. 42
4.9. ASSAY (UV) ........................................................................................................ 43
4.9.1 Assay of Paracetamol Tablets by UV .................................................................45
4.10 Calibration Curve for Dissolution ........................................................................ 47
4.10.1 Calibration Curve for Paracetamol in Phosphate Buffer pH 5.8 at 237 nm ......47
4.10.2 In vitro Dissolution Studies ...............................................................................48
4.11 Percentage Drug Release ..................................................................................... 50
CHAPTER FIVE .......................................................................................................64
DISCUSSION .............................................................................................................64
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5.1 Conclusions ............................................................................................................ 71
5.2 Recommendations .................................................................................................. 72
REFERENCES ...........................................................................................................73
APPENDICES ............................................................................................................82
Appendix A .................................................................................................................. 82
Appendix B .................................................................................................................. 95
Appendix C .................................................................................................................. 96
Appendix D ................................................................................................................ 103
Appendix E ................................................................................................................ 105

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LIST OF TABLES
Table 2.1 Some Important Wave numbers and their Functional Groups .................... 19
Table 1.2 Permissible percentage deviation of tablet for uniformity of weight test
(USP 2007)................................................................................................. 22
Table 3.1 Profiles of Paracetamol Brands Sampled and Analyzed ............................. 29
Table 3.2 „P‟ values Interpretation ............................................................................... 35
Table 4.1 Thickness of the various brands of Paracetamol tablets (n=20) .................. 36
Table 4.2 Diameter of the various brands of Paracetamol tablets (n=20) ................... 37
Table 4.3 Uniformity of Weight of the different Brands of Paracetamol Tablets (n=20)
.................................................................................................................... 38
Table 4.4 Friability of the Paracetamol Tablets (n=20) ............................................... 39
Table 4.5 (Crushing strength) Hardness of the Paracetamol Tablets (n=20) ............... 40
Table 4.6 Crushing strength friability ratio of Paracetamol tablet (n=20) ................... 41
Table 4.7 Disintegration Time of the Paracetamol Tablets (n=6) ............................... 42
Table 4.8 Concentration against Absorbance for Calibration Curve for Paracetamol 43
Table 4.9 Assay of Paracetamol Tablets by UV .......................................................... 45
Table 4.10 Conc. against absorbance for calibration curve of Paracetamol ................ 47
Table 4.11 Percentage Drug Release of all Brands of Paracetamol Tablets Phosphate
Buffer pH 5.8 (n=6) ................................................................................... 50
Table 4.12 Summary of Test Conducted on the Paracetamol Brands ......................... 56
Table 4.13 Comparison of Reference drug, PMA against Test Drugs using one-way
ANOVA followed by Dunnett‟s test.......................................................... 57
Table 4.14 Comparison of Reference Drug, PMA against Test Drugs using one-way
ANOVA followed by Dunnett‟s test.......................................................... 58
Table 4.15 Comparison of Reference Drug, PMA against Test Drugs using one-way
ANOVA followed by Dunnett‟s Test ........................................................ 59
Table 4.16 Comparison of Reference Drug, PMA against Test Drugs using one-way
ANOVA followed by Dunnett‟s Test ........................................................ 60
Table 4.17 Comparison of Reference Drug, PMA against Test Drugs using one-way
.................................................................................................................... 61
Table 4.18 Comparison of Reference Drug, PMA against Test Drugs using one-way
ANOVA followed by Dunnett‟s test.......................................................... 62
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