Abstract

ENHANCEMENT OF SOLUBILITY OF EFAVIRENZ EMPLOYING ? CD AND SLS: OPTIMIZATION BY 22 FACTORIAL DESIGN

K. P. R. Chowdary*, M. Ravi Kumar and Ch. P. S. R. Madhuri

Abstract

Efavirenz, a widely prescribed HIV-1 specific, non nucleoside reverse transcriptase inhibitor (NNRTI) drug belong to Class II under BCS and exhibit low and variable oral bioavailability due to its poor aqueous solubility. Its oral absorption is dissolution rate limited and it requires enhancement in solubility for increasing its oral bioavailability and therapeutic efficacy. The objective of the present study is to enhance the solubility of efavirenz by employing β-cyclodextrin (β CD) and sodium lauryl sulphate (SLS) .The individual main and combined (interaction) effects of β CD and SLS on the solubility of efavirenz were evaluated in a 22 factorial study. The solubility of efavirenz in the selected four fluids as per 22 factorial design was determined (n=3). Optimization of factors (β CD and SLS) to achieve the desired solubility of efavirenz was done by fitting a polynomial equation to the observed data. The solubility of efavirenz was markedly increased by both β CD and SLS. The main and combined effects of β CD and SLS in enhancing the solubility of efavirenz were highly significant (P < 0.01). SLS alone and in combination with β CD gave higher enhancement in the solubility of efavirenz. The increasing order of solubility observed with various fluids was F a b> F b> F1> F a. 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 = 184.75+15.75 (X1) +113.75 (X2) + 45.75 (X1 X2). SLS (X2) has greater effect in increasing the solubility of efavirenz, followed by combination of β CD and SLS (X1 X2) and β CD (X1). Based on the above polynomial equation two optimized solutions, one with high solubility (260mg / 100ml) and the other with moderate solubility (200mg / 100ml) of efavirenz were prepared and the solubility of efavirenz in the two solutions was determined (n=3). The experimentally determined solubility values are in close agreement with the predicted or optimized solubility values. The results indicated validity of the optimization technique employed and the polynomial equation developed could be used to develop solutions with any desired solubility specification.

Keywords: Efavirenz, Solubility, ? cyclodextrin, Sodium lauryl sulphate, Optimization, Factorial design.