1. 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

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

3. INTRODUCTION Synthetic antimicrobials derived from quinolones

4. 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

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

6. 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

7. 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

8. 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

9. RESULTS Brand Code Average Uniformity of Weight (mg) (X ± 5 %) Hardness (N) (Average) Disintegration Time (Min) Assay (%) C001777.16141.831.596.80 C002899.08188.3312.098.44 C003770.75176.670.894.83 C004743.65193.171.597.26 C005635.78119.333.098.20 C006739.52187.672.295.86 C007783.13180.170.597.26 C008740.94190.502.797.21 C009694.67145.832.399.37 C010679.70164.501.298.78

10. RESULTS…CTD Brand Code Average Uniformity of Weight (mg) (X ± 5 %) Hardness (N) (Average) Disintegration Time (Min) Assay (%) C011969.85158.171.297.03 C012643.05148.006.094.45 C013823.01109.1723.5104.58 C014827.13189.003.599.59 C0151033.82166.173.299.18 C0161064.30144.171.095.49 C017745.43186.671.398.62 C018692.2262.006.590.38 C019730.57142.331.394.97 IB762.49176.670.598.57

11. RESULTS…CTD Brand codepH 1.2pH 4.5pH 6.8 C001 95.81 96.6232.16 C002 90.69 87.974.38 C003 92.17 93.225.02 C00482.4894.3847.39 C00590.9694.8538.32 C00693.3597.0251.50 C00783.4696.5155.41 C00898.3597.2447.72 C00994.7397.4629.24 C01088.8196.2446.09 Amount released in % at 30 min

12. RESULTS…CTD Brand codepH 1.2pH 4.5pH 6.8 C01197.2091.3810.46 C01277.6894.327.06 C013101.3773.731.65 C01494.0295.61.75 C01552.8580.447.14 C01679.3281.5721.41 C01784.9594.5059.02 C01888.6588.247.57 C01991.3195.4143.45 IB91.4894.8335.33 Amount released in % at 30 min

13. RESULTS…CTD Brand codepH 1.2pH 4.5pH 6.8 C00144.34 61.3173.07 C00256.15 61.5425.60 C00360.55 55.6825.82 C00453.54 65.9046.14 C00557.94 54.6879.00 C00658.90 84.5040.64 C00756.51 55.6734.97 C008 42.9371.1147.21 C009 61.9268.0457.10 C010 67.6874.6350.32 Similarity factors (f 2 ) of Ciprofloxacin tablet brands

14. RESULTS…CTD Brand codepH 1.2pH 4.5pH 6.8 C011 60.5045.9130.26 C012 30.6733.8327.14 C013 46.9118.2323.83 C014 39.9129.2423.86 C015 19.0421.0227.59 C016 50.4630.1641.46 C017 58.7376.0731.50 C018 47.1742.9826.90 C019 62.0781.7955.14 Similarity factors (f 2 ) of Ciprofloxacin tablet brands

15. 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

16. 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

17. 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

18. 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

19. THANK YOU