Postmarketing In Vitro/In Vivo Assessment of Fixed Dose Combination Products of First Line Antiretrovirals

The purpose of this study was to evaluate the postmarket pharmaceutical equivalence, stability and bioequivalence of generic and innovator fixed dose combination products of lamivudine (3TC) and zidovudine (AZT) 150/300 mg tablets available in Nigeria. An isocratic HPLC-UV method was developed and validated for the quantitative determination of 3TC and AZT in human plasma and pharmaceutical samples. The model independent f2 similarity factor was used to compare the dissolution profiles of the two products stored at accelerated and longterm stability conditions for 6 months. The f2 values for 3TC and AZT in both products were found to be greater than 51. Also, the tablets were stable according to the USP potency and drug dissolution criteria with more than 80% of drug dissolution in 30 min indicating the pharmaceutical equivalence of the two products. The 90% confidence interval for the ratios of generic/innovator pharmacokinetic parameters for 3TC/AZT were 73.5-112.6/63.4-95.8 (Cmax); 68.5-105.6/68.0-114.8 (AUC0-t); and 64.2-106.2/80.1-120.3 (AUC0-∞) respectively. The pharmacokinetic parameters failed to fully demonstrate bioequivalence between the products. The results underscored the importance of assessing the quality of the combination drug products that would ensure the safety and efficacy of the generic drug products available in the market.