COMPARATIVE IN VITRO EVALUATION

OF GENERIC CIPROFLOXACIN HYDROCHLORIDE TABLETS IN KENYA

BYDANIEL MINYETOU59/81286/2012

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 OBJECTIVESGeneral objectiveTo 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® C18

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

RESULTSBrand Code

Average Uniformity of Weight (mg)

(X ± 5 %)

Hardness (N)(Average)

Disintegration Time (Min)

Assay (%)

C001 777.16 141.83 1.5 96.80

C002 899.08 188.33 12.0 98.44

C003 770.75 176.67 0.8 94.83

C004 743.65 193.17 1.5 97.26

C005 635.78 119.33 3.0 98.20

C006 739.52 187.67 2.2 95.86

C007 783.13 180.17 0.5 97.26

C008 740.94 190.50 2.7 97.21

C009 694.67 145.83 2.3 99.37

C010 679.70 164.50 1.2 98.78

RESULTS…CTDBrand Code

Average Uniformity of Weight (mg)

(X ± 5 %)

Hardness (N)(Average)

Disintegration Time (Min)

Assay (%)

C011 969.85 158.17 1.2 97.03

C012 643.05 148.00 6.0 94.45

C013 823.01 109.17 23.5 104.58

C014 827.13 189.00 3.5 99.59

C015 1033.82 166.17 3.2 99.18

C016 1064.30 144.17 1.0 95.49

C017 745.43 186.67 1.3 98.62

C018 692.22 62.00 6.5 90.38

C019 730.57 142.33 1.3 94.97

IB 762.49 176.67 0.5 98.57

RESULTS…CTD

Brand code pH 1.2 pH 4.5 pH 6.8

C001 95.81 96.62 32.16

C002 90.69 87.97 4.38

C003 92.17 93.22 5.02

C004 82.48 94.38 47.39

C005 90.96 94.85 38.32

C006 93.35 97.02 51.50

C007 83.46 96.51 55.41

C008 98.35 97.24 47.72

C009 94.73 97.46 29.24

C010 88.81 96.24 46.09

Amount released in % at 30 min

RESULTS…CTD

Brand code pH 1.2 pH 4.5 pH 6.8

C011 97.20 91.38 10.46

C012 77.68 94.32 7.06

C013 101.37 73.73 1.65

C014 94.02 95.6 1.75

C015 52.85 80.44 7.14

C016 79.32 81.57 21.41

C017 84.95 94.50 59.02

C018 88.65 88.24 7.57

C019 91.31 95.41 43.45

IB 91.48 94.83 35.33

Amount released in % at 30 min

RESULTS…CTD

Brand code pH 1.2 pH 4.5 pH 6.8

C001 44.34 61.31 73.07

C002 56.15 61.54 25.60

C003 60.55 55.68 25.82

C004 53.54 65.90 46.14

C005 57.94 54.68 79.00

C006 58.90 84.50 40.64

C007 56.51 55.67 34.97

C008 42.93 71.11 47.21

C009 61.92 68.04 57.10

C010 67.68 74.63 50.32

Similarity factors (f2) of Ciprofloxacin tablet brands

RESULTS…CTD

Brand code pH 1.2 pH 4.5 pH 6.8

C011 60.50 45.91 30.26

C012 30.67 33.83 27.14

C013 46.91 18.23 23.83

C014 39.91 29.24 23.86

C015 19.04 21.02 27.59

C016 50.46 30.16 41.46

C017 58.73 76.07 31.50

C018 47.17 42.98 26.90

C019 62.07 81.79 55.14

Similarity factors (f2) 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

THANK YOU