Bioavailability of locally manufactured co-trmoxazole tablets

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Pertinent bioavailability and bioequivalent data are required by Pharmacist, Physicians, and others who prescribe, dispense or purchase drug products. This is because a plethora of drug products containing the same amount of active ingredients have flooded the Ghanaian market. The bioequivalence of generic co-trimoxazole and reference (Septrin- GlaxoWeilcome) was compared in six healthy subjects in a crossover design using the amount of the unchanged sulphamethoxazole excreted in urine over 24 hours. The generic product was from Phyto-Riker (GIHOC). It was designated in the study as S. The reference product was designated as R and it was purchased from S. K. Osei Pharmacy, a retail pharmacy shop at Adehyeman Gardens opposite the Methodist Book Depot in Kumasi. ln vitro dissolution test was also carried out. With reference to the product R, the relative bioavailability of product S was 109.23. An HPLC method for determining accurately and precisely sulphamethoxazole in urine was tried and used. Phermacokinetic variables that were tested to characterize bioequivalence were the mean cumulative amount of unchanged sulphamethoxazole excreted, the mean peak rate of urinary excretion, and the time for peak urinary excretion. In order to ensure that any difference observed in the in vivo study among the products were not due to sample identity and formulation factors, pharmacopoeial identification tests, uniformity of weight, friability and hardness tests, dissolution and percent content assay were performed on all the drug products. For all tested products, the results of sample identification, uniformity of weight, dissolution, friability test and hardness test as well as percent content assays were within acceptable limits of BP 2000 and USP XXII (1980). Pharmacokinetic variables tested showed no significant difference between the products S and R. The generic product was therefore fully bioequivalent with the reference product. An HPLC separation and resolution could be achieved with a mobile phase combination of ethanol and 70% ammonium perchiorate ( 95 : 5) on a reversed phase column at ambient temperature. Elution was socratic with UV detection wavelength of 254nrn Internal standard calibration method was used for quantification with Salicylic acid as the internal standard. Mean retention times for trimethoprim, sulphamethoxazole and salicylic acid were 3.4 ± 0.125 mm, 3.8 ± 0.075 mm, and 4.5 ± 0.125 mm respectively. Assaying the two products with the new HPLC method and the official BP 2000 method yielded t-values of 1.52 and 0.858 in test and reference respectively. This means these two methods were comparable at 95% confidence level. Also the percentage content each of active ingredient in test and reference samples by both methods fell within acceptable limits of BP 2000 and the USP-XXII (1980) limit.
A thesis submitted to the College of Health Sciences in partial fulfilment for the requirements for the degree of Master of Science, 2005