Abstract

PRECLINICAL PHARMACOKINETIC EVALUATION OF RITONAVIR TABLETS FORMULATED EMPLOYING ? CD AND SOLUPLUS

K. Ravi Shankar, Dr. KPR Chowdary* and A. Sambasiva Rao

ABSTRACT

Ritonavir, a widely prescribed BCS class II antiretroviral drug exhibit low and variable oral bioavailability due to its poor aqueous solubility and needs enhancement in the dissolution rate in its formulation development. We have earlier reported optimization of ritonavir tablet formulation employing β CD and Soluplus to achieve NLT 85 percent dissolution in 15 min by 22 factorial design. The optimized ritonavir (50 mg) tablet formulation prepared employing βCD (137.5 mg /tablet) and Soluplus (0.75 mg/ tablet) gave 86.25 % dissolution in 15 min fulfilling the target dissolution set. The objective of the present study is pharmacokinetic evaluation of optimized ritonavir tablets formulated employing βCD and Soluplus for their in vivo performance in comparison to plain tablets in healthy rabbits. The study was carried out as per a cross over design. The elimination characteristics of ritonavir have not changed when it was formulated as optimised tablets with βCD and Soluplus. Optimised ritonavir tablets gave rapid and higher absorption and bioavailability of ritonavir when compared to plain tablets. A 5.52 fold and 1.67 fold increase in absorption rate ( Ka) and (AUC) âˆÅ¾0 was observed with optimised ritonavir tablets formulated with βCD and Soluplus when compared to plain tablets.

Keywords: Ritonavir, Pharmacokinetics, Optimization, Pre-clinical Evaluation, ? Cyclodextrin.