COMPARATIVE IN VITRO EVALUATION OF GENERIC CIPROFLOXACIN HYDROCHLORIDE TABLETS IN KENYA BY DANIEL MINYETO U59/81286/2012 Department of Pharmaceutical Chemistry School of Pharmacy UNIVERSITY OF NAIROBI November 13, 2014

OUTLINE Introduction Study justification Study objectives Experimental Results and discussion Conclusion Recommendations Acknowledgements

INTRODUCTION Synthetic antimicrobials derived from quinolones

INTRODUCTION…CTD Spectrum of activity: Both Gram-positive and Gram-negative bacteria Classification: Based on antibacterial activity; from first to fourth generations Mechanism of action: Inhibits protein synthesis Stability: Photodegradation Solubility: Almost insoluble in water; shows highest solubility at pH 4 - 5

STUDY JUSTIFICATION Ciprofloxacin is the most prescribed fluoroquinolone Listed as an essential drug by WHO and MoH Kenya Increased number of generics, influx of counterfeits and substandard products No previous bioequivalence studies on ciprofloxacin

STUDY OBJECTIVES General objective To determine the quality of marketed ciprofloxacin tablets in Nairobi, Kenya Specific objectives To carry out tests for identity, uniformity of weight, hardness, disintegration and assay of brands of ciprofloxacin tablets To carry out comparative dissolution testing of the generic and innovator ciprofloxacin tablets To determine pharmaceutical equivalence of generic brands of ciprofloxacin tablets

EXPERIMENTAL Sampling: 500 mg ciprofloxacin tablets were purchased from randomly selected pharmacies in Nairobi Central Business District Weight uniformity determination: BP method Hardness test: USP method Disintegration test: BP method Assay: USP method Chromatographic conditions: Symmetry® C 18 column (250 × 4.6 mm × 5μm), 10 µL injection volume, 1.5 mL/min flow rate, temp 30 ± 1 °C, UV detection at 278 nm

EXPERIMENTAL…CTD Dissolution; USP method (USP apparatus 2) Media: USP buffer solutions at pH 1.2, 4.5 and 6.8 Six tablets were used for each brand Six sampling points UV/VIS spectrophotometer

RESULTS Brand Code Average Uniformity of Weight (mg) (X ± 5 %) Hardness (N) (Average) Disintegration Time (Min) Assay (%) C C C C C C C C C C

RESULTS…CTD Brand Code Average Uniformity of Weight (mg) (X ± 5 %) Hardness (N) (Average) Disintegration Time (Min) Assay (%) C C C C C C C C C IB

RESULTS…CTD Brand codepH 1.2pH 4.5pH 6.8 C C C C C C C C C C Amount released in % at 30 min

RESULTS…CTD Brand codepH 1.2pH 4.5pH 6.8 C C C C C C C C C IB Amount released in % at 30 min

RESULTS…CTD Brand codepH 1.2pH 4.5pH 6.8 C C C C C C C C C C Similarity factors (f 2 ) of Ciprofloxacin tablet brands

RESULTS…CTD Brand codepH 1.2pH 4.5pH 6.8 C C C C C C C C C Similarity factors (f 2 ) of Ciprofloxacin tablet brands

DISCUSSION All analyzed ciprofloxacin brands complied for uniformity of weight, hardness, disintegration, identification and assay There was significant variability in in-vitro drug release at different pH values Ten brands (52.63 %) met specifications for similarity

CONCLUSION Not all ciprofloxacin brands on the Kenyan market meet quality standards Not all brands can be used interchangeably with the innovator brand Dissolution profiling should be done at more than one pH value

RECOMMENDATIONS Further studies should be done to establish a meaningful correlation between in vitro and in vivo bioavailability parameters Quality of essential drugs should be continuously monitored through post marketing surveillance

ACKNOWLEDGEMENTS Supervisors Dr. S.N. Ndwigah Dr. P.M. Njogu Dr. H.K. Chepkwony NQCL management and technical staff Mr. Cosmas Rotich University of Gulu

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