Abstract

OPTIMIZATION OF EFAVIRENZ TABLET FORMULATION EMPLOYING ? CD AND SOLUPLUS BY 22 FACTORIAL DESIGN

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

ABSTRACT

Efavirenz, a widely prescribed antiretroviral drug belongs to class II under BCS classification and exhibit low and variable oral bioavailability due to its poor aqueous solubility. It needs enhancement in the dissolution rate in its formulation development. Complexation with β-cyclodextrin (βCD) and use of surfactant (Soluplus) are tried for enhancing the dissolution rate of efavirenz in its formulation development. The objective of the present study is optimization of efavirenz tablet formulation employing βCD and Soluplus by 22 factorial design. Formulation of efavirenz tablets with NLT 85% dissolution in 15 min employing βCD and Soluplus was optimized by 22 factorial design. Four efavirenz (50 mg) tablet formulations were prepared using selected combinations of the two factors as per 22 factorial design. Efavirenz tablets were prepared by direct compression method and were evaluated for drug content, hardness, friability, disintegration time and dissolution rate characteristics. All the efavirenz tablets prepared fulfilled the official (IP 2010) requirements with regard to drug content, hardness, friability and disintegration time specified for uncoated tablets. Much variations were observed in the disintegration and dissolution characteristics of the efavirenz tablets prepared due to formulation variables. The disintegration times were in the range 25 sec to 6 min 30 sec with various tablets. Efavirenz tablets (Eb) which are prepared employing βCD in 1:0.5 ratio of drug: βCD and Soluplus at 2 % of drug content gave very rapid dissolution of efavirenz than others. These tablets (Eb) gave 99.65 % dissolution in 15 min. The increasing order of dissolution rate (K1) observed with various formulations was Eb>Eab > Ea > E1. For optimization, percent drug dissolved in 15 min was taken as response (Y) and level of βCD as (X1) and level of Soluplus as (X2). The polynomial equation describing the relationship between the response, Y and the variables, X1 and X2 based on the observed data was found to be Y = 69.88 + 8.68 (X1) + 24.9 (X2) – 13.56 (X1 X2). Based on the above polynomial equation, the optimized efavirenz tablet formulation with NLT 85% dissolution in 15 min could be formulated employing βCD at 1:2.75 ratio of drug: βCD and Soluplus at 1.64 % of drug content. The optimized efavirenz (50 mg) tablet formulation prepared employing βCD (137.5 mg / tablet) and Soluplus (0.82 mg/ tablet) gave 85.69% dissolution in 15 min fulfilling the target dissolution set. Thus optimization by 22 factorial design could be successfully used for the development of efavirenz tablets with NLT 85 % dissolution in 15 min

Keywords: Efavirenz tablets, Optimization, ?-cyclodextrin, Soluplus, Factorial Design.