– Comparative Bioequivalence Studies of Some Selected Brands of Ciprofloxacin Tablets Marketed In Zaria –
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ABSTRACT
Comparative bioequivalence studies of six selected brands of ciprofloxacin tablets was successfully conducted. In-vitro quality control studies were carried out on six randomly selected brands of ciprofloxacin to establish identity, weight uniformity, friability, crushing strength, disintegration, dissolution and assay according to BP 2002 and 2009.
Cheap, simple and available method of analysis of ciprofloxacin in saliva sample was developed by U.V Spectrophotometer with variable wavelengths.
The developed method was validated based on ICH guidelines. Bioequivalence parameters (Cmax, Tmax and AUC) were evaluated on the six brands of ciprofloxacin to determine their interchangeability after a wash-out period of one week.
From the result of in-vitro studies all brands passed the test indicating pharmaceutical equivalence. All the brands were found to have the labeled active ingredient as they were within the accepted range of 95-105%.
The percentage recovery was within the accepted range of 95 – 105%. Calibration curve was constructed and was linear within the range of 1-6µg/ml as the correlation coefficient was 0.9889.
TABLE OF CONTENTS
Title page………………..i
Declaration……………..ii
Certification………..… iii
Acknowledgement……..iv
Dedication…………………v
Abstract……………………vi
Table of contents…………viii
List of Tables…………………xiii
List of Figures…………………. xiv
Abbreviations……………………xv
Equations…………………………xvi
List of Appendices……………….xvii
CHAPTER ONE
1.0 INTRODUCTION……………1
1.1 Preamble……………………………1
1.2 Statement of Research Problem……………5
1.3 Justification………………..5
1.4 Aims and Objectives of the Study………………….6
1. 5 Hypothesis……………….6
CHAPTER TWO
2.0 LITERATURE REVIEW………….7
2.1 Bioequivalence………………….7
2.1.1 Regulatory Definition…………7
2.2 Ciprofloxacin…………………9
2.2.1 Description……………………9
2.2.2 Clinical pharmacology…………10
2.2.3 Antimicrobial Action ………………13
2.2.4 Uses and Administration.………….15
2.2.5 Contraindications…………….…..16
2.2.6 Precautions……………………..17
2.2.7 Adverse reaction………………18
2.2.8 Overdosage…………………20
2.3 Saliva as an analytical tool………..20
2.3.1 The collection and analysis of saliva…………21
2.3.2 Mechanism of drug transfer from blood to saliva………..23
2.4 Spectroscopy……………24
2.4.1 Ultraviolet Visible spectroscopy……………24
2.4.2 Beer’s law…………………25
2.4.3 Lambert’s law………….25
2.4.4 Beer-Lambert’s Law………..26
2.5 Quality Control of Tablets (evaluation tests)………. 26
2.5.1 General appearance…………….27
2.5.2 Non-official tests……………..28
2.5.3 Hardness (crushing test)…………..28
2.5.4 Friability………………30
2.2.5 Official tests…………30
2.5.6 Disintegration…………30
2.5.7 Dissolution……………….31
2.5.8 Weight variation or uniformity of weight………32
2.5.9 Content uniformity……………..33
2.6 Analytical Procedures…………..…34
2.6.1 Types of analytical procedures to be validated……….34
2.6.2 Validation of analytical methods and characteristics…………….36
CHAPTER THREE
3.0 MATERIAL AND METHODS………..40
3.1 Materials…………..40
3.1.1 Drugs………..40
3.1.2 Glassware accessories…………42
3.1.3 Equipments…………43
3.1.4 Reagents………….44
3.2 Subjects………………44
3.3 Methodology…………45
3.3.1 Sample Collection……45
3.3.2 In-vitro quality control (BP 2002, 2009)…….45
3.3.3 Development and validation of the analytical methods……..48
3.3.4 Validation of the developed methods…….. 49
3.3.5 Extraction method…………..50
3.3.6 Percentage recovery……………50
3.3.7 Calibration curve……………..51
3.3.8 Study design……………..51
3.3.9 Data analysis………….52
CHAPTER FOUR
4.0 RESULTS……………..53
4.1 In-vitro quality control……………….53
4.1.1 Physical identity of samples…………..53
4.1.2 Identification of Ciprofloxacin Hydrochloride powder (chloride test)…….. 54
4.1.3 Mean weight variation……………55
4.1.4 Percentage friability……………….56
4.1.5 Mean crushing strength…………57
4.1.6 Mean disintegration (mins)…………58
4.1.7 Dissolution……………..………………59
4.1.8 Assay of innovator and test brands of Ciprofloxacin………..60
4.2 Development and validation of the analytical method……….61
4.2.1 Development of the analytical methods………………… 61
4.2.2 Effect of pH on wavelength of maximum absorption ……………..63
4.2.3 Precision of the analytical method………………65
4.2.4 Accuracy and percentage recovery of standard Ciprofloxacin Hydrochloride……..66
powder spiked in blank saliva
4.2.5 Validation parameters of the developed method………….67
4.3.6 Calibration curve………………….68
4.3 In-vivo result………………70
4.3.1 Pharmacokinetic parameters of various brands of Ciprofloxacin tablets………..70
4.3.2 Bioequivalence ratio of reference and test brands……………..71
CHAPTER FIVE
5.0 DISCUSSION………74
CHAPTER SIX
6.0 CONCLUSION……….80
RECOMMENDATIONS…………81
REFERENCES…………………82
INTRODUCTION
There is growing trade in substandard and counterfeit drugs including antibiotics aroundthe world. The prevalence of such substandard drugs in Nigerian markets has beenworrisome to both regulatory agencies and all concerned.
The availability of drugs, especially antibiotics in open markets has led to indiscriminate use and may contribute tohigh incidence of antibiotic-resistant strains (Mukhtar et al., 2010).
The need to select one product from several generic drug products of the same active ingredients during thecourse of therapy is also a cause for concern to healthcare practitioners (Adegbolagun etal., 2007).
Generic drug is a product sold under the chemical name of a branded drug, after theexpiry of the patent for a branded drug.
Both the branded and the generic versions musthave the same potency, be available in the same dosage forms (i.e. tablets, liquids,injectables) and be demonstrated to be safe and effective.
The generic drugs are lessexpensive as compared to branded drugs as generic manufacturers do not have theinvestment costs of the developer of a new drug.
New drugs are generally developedunder patent protection. Generic drugs are usually far cheaper than branded drugs,sometime up to 90%.
Efficacy and safety of pharmaceutical product depend on its standards preset to assure the desired purpose.
REFERENCE
Adegbolagun,O.A, Olalade,O.A, Osumah, S.E. (2007). Comparative evaluation of the biopharmaceutical and chemical equivalence of some commercially available brands of ciprofloxacin hydrochloride tablets.Tropical Journal of Pharmaceutical Research, 6(3): 737-745
Adnan A. K, Badraddin M. A., Mohamed W. A., Ali S. A., Yousry M. El., Mohamed I.A.m (2013). Comparative bioequivalence evaluation of two brands of ofloxacin 200mg tablets (Jedcoflacin vs Tarivid) in 24 health volunteers: a randomized, single dose, two period, and two sequence cross-over studies. Digest journal of nanomaterials and biostructure, 8(1):239-246
Akinleye M.O., Coker H.A.B., Chukwuani C.M., Adeoye A.W. (2007). Effect of Five alive® fruit juice on the dissolution and absorption profiles of Ciprofloxacin. Nigerian quarterly journal of hospital medicine, 17(1):53-57
Bayer Healthcare pharmaceuticals (2009).CIPRO (ciprofloxacin hydrochloride) Tablets and CIPRO (ciprofloxacin hydrochloride) Oral Suspension.Ciprofloxacin medication guide. Retrieved from http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=888dc7f9-ad9c-4c00- 8ddfd9bd27c0. Retrieved 14/4/2013
Behera S., Subhajit G., Fahad A., Saayak S., Sritoma B. (2012).UV-Visible Spectrophotometric Method Development and Validation of Assay of Paracetamol Tablet Formulation. Journal Analytical and Bioanalalytical Techniques, 3(6):2-6
Birkett,D.J. (2003). “Generics – equal or not?”.Australian Prescriber, 26(4): 85–7 British Pharmacopoeia (2009). Medicinal and Pharmaceutical Substances, (pp. 1381-85, 8351 – 8353).