Abstract

A FACTORIAL STUDY OF FORMULATION OF RITONAVIR TABLETS EMPLOYING ? CYCLODEXTRIN, SOLUPLUS AND PVP K30

K. Ravi Shankar, K. P. R. Chowdary* and A. Sambasiva Rao

ABSTRACT

Ritonavir, a widely prescribed protease inhibitor drug belongs to class IΙ under BCS and exhibit low and variable oral bioavailability due to its poor aqueous solubility. It is practically insoluble in water and aqueous fluids and as such it posses challenging problems in its formulation development. The objective of the present study is to formulate ritonavir tablets with fast dissolution characteristics employing β cyclodextrin (β CD), Soluplus and PVP K30 alone and in combinations and to evaluate their effects on the dissolution rate of ritonavir tablets in a 23 factorial study. Ritonavir tablets were formulated employing β CD, Soluplus and PVP K 30 as per 23 factorial design and the tablets were prepared by direct compression method. The tablets prepared were evaluated for various physical properties, dissolution rate and dissolution efficiency. Dissolution data were analyzed by Analysis of Variance (ANOVA) of 23 factorial studies. Ritonavir – βCD – Soluplus- PVP K 30 solid inclusion complexes could be formulated into compressed tablets by direct compression method and the resulting tablets fulfilled the official (IP 2010) specifications with regard to hardness, friability, drug content, disintegration time and dissolution rate . The individual as well as combined effects of the three factors involved i.e., βCD (factor A) ,Soluplus (factor B) and PVP K 30 ( factor C) were highly significant (P< 0.01) in enhancing the dissolution rate (K1) and dissolution efficiency (DE 30) of ritonavir. Tablets formulated employing ritonavir- β CD – Soluplus and ritonavir- β CD- PVP K30 ternary complexes gave much higher enhancement in the dissolution rate of ritonavir tablets than those formulated employing ritonavir - β CD binary complexes. There was no further increase in the dissolution rate with tablets formulated employing ritonavir – β CD - Soluplus - PVP K 30 quaternary complexes. DE30 values were also much higher in the case of ritonavir tablets formulated employing drug- βCD – Soluplus and drug- βCD -PVP K 30 solid complexes when compared to ritonavir plain tablets. Tablets formulated employing drug – β CD - Soluplus , drug – β CD - PVP K 30 and drug – β CD - Soluplus - PVP K 30 fulfilled the official dissolution rate test specification, whereas tablets formulated employing drug- β CD binary complexes did not fulfill the official dissolution rate specification. Combination of βCD with either Soluplus or PVP K 30 is recommended in the formulation development of ritonavir tablets to enhance their dissolution rate and dissolution efficiency.

Keywords: Ritonavir tablets, Formulation development, ? cyclodextrin, Soluplus, PVP K30, Dissolution rate, Factorial study.