Abstract

ENHANCEMENT OF SOLUBILITY AND DISSOLUTION RATE OF EFAVIRENZ EMPLOYING ?CD , LUTROL, POLOXAMER AND GELUCIRE ALONE AND IN COMBINATION

V. Chaitanya*, P. Narahari Narayan, Sunil Kumar and K.P.R Chowdary

ABSTRACT

Efavirenz, a widely prescribed anti-retroviral drug belongs to class-II under BCS and exhibit low and variable oral bioavailability due to its poor aqueous solubility. As such it needs enhancement in the solubility and dissolution rate in its formulation development to derive its maximum therapeutic efficacy. The objective of the present study is enhancement of solubility and dissolution rate of efavirenz employing βCD and three surfactants namely (i) Lutrol 400, (ii) Poloxamer 188 and (iii) Gelucire 44/12 alone and in combination. The individual and combined effects of βCD and surfactant in enhancing the solubility and dissolution rate of efavirenz in each case were evaluated in a series of 22-factorial studies. A comparative evaluation of the effects of βCD and the three surfactants alone and in combination in enhancing the solubility and dissolution rate of efavirenz was made. Among the βCD and three surfactants alone, Gelucire 44/12 gave highest enhancement in aqueous solubility of efavirenz (3.57 fold). The order of increasing solubility observed with βCD and various surfactants alone was Gelucire > Poloamer > βCD > Lutrol. In the case of βCD- surfactant combinations, βCD-Gelucire gave 4.14 fold, βCD- Poloxamer gave 3.29 fold and βCD- Lutrol gave 0.63 fold increase in the aqueous solubility of efavirenz. Among the βCD and the three surfactants alone, Lutrol gave highest enhancement in the dissolution rate of efavirenz. The order of increasing dissolution rate observed with βCD and various surfactants was Lutrol > βCD > Gelucire > Poloxamer. In the case of βCD- surfactant complexes, βCD- Lutrol gave 6.91 fold, βCD-Gelucire gave 3.05 fold and βCD- Poloxamer gave 2.68 fold increase in the dissolution rate of efavirenz. The dissolution efficiency (DE20) was also higher in case of βCD- surfactant complexes when compared to efavirenz pure drug. ANOVA indicated that the individual and combined effects of βCD and surfactant in enhancing the solubility and dissolution rate of efavirenz were highly significant (P < 0.01) in each case. Overall, surfactants Gelucire and Poloamer alone and βCD in combination with Lutrol,Gelucire and Poloxamer are recommended to enhance the solubility and dissolution rate of efavirenz, a p.oorly soluble BCS class II drug.

Keywords: Efavirenz, ? Cyclodextrin, Lutrol , Poloamer, Gelucire, Solubility, Dissolution Rate, Factorial Study.