Pharmacokinetic Boosting of Zidovudine for HIV Treatment

Abstract

The aim of the present study was to develop “Pharmacokinetic boosting model of Zidovudine for HIV treatment”.Zidovudine was combined with Ketoconazole as once daily sustained release matrix tablets for pharmacokinetic boosting of Zidovudine, Ketoconazole inhibits CYP 3A4 enzyme responsible for metabolising Zidovudine hence boosts its plasma concentration , facilitate treatment of fungal infection which are prevalent during AIDS. Further this formulation increase therapeutic efficacy, reduce frequency of administration and improve patient compliance. The sustained release tablets were prepared by wet granulation method. By using different drug: polymer ratios, formulations F1 to F8 were prepared. Hydrophilic polymers like hydroxy propyl methyl cellulose (HPMC K4M), ethyl cellulose, PVPK-30 were used. Compatibility of the drug with various excipients was studied. The compressed tablets were evaluated and showed compliance with pharmacopoeial standards. Formulation containing 30% polymer mixture of HPMCK4M and Ethyl cellulose in ratio 1:1, with hardness 7.11±0.324 kg/cm2showed the desired release profile which matched the theoretical release profile. In- vitro drug release characteristics were studied for a period of 12 hr using USP Type 2 dissolution apparatus. In Vivo studies of formulation F7 were performed on Rabbit.Plasma samples were analysed using HPLC. It was found that on administering single tablet of 300 mg AUC at tp was found to be 237795 as in HPLC chromatogram and on administering F7 formulation containing Zidovudine and Ketoconazole in ratio 3:2, AUC at tp was found to be 329095 . This shows significant pharmacokinetic boosting.