Abstract

Formulation Development of Efavirenz Tablets Employing HP Ã?Â? Cyclodextrin-PVP K30-SLS: A Factorial Study

Author(s): K. P. R. Chowdary and A. Naresh

Efavirenz, a widely prescribed anti-retroviral drug belongs to class IΙ 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 the solubility and dissolution rate for increasing its oral bioavailability. The objective of the study is to evaluate the feasibility of formulating efavirenz-HPβCDPVP K30/SLS inclusion complexes into tablets and to evaluate the effects of HPβCD, PVP K30 and SLS on the dissolution rate and dissolution efficiency of efavirenz tablets in a 23 factorial study. A comparative evaluation of wet granulation and direct compression methods was made for the preparation of tablets employing drug-HPβCD-PVP K30/SLS inclusion complexes. Drug-HPβCD-PVP K30/SLS inclusion complexes were prepared by kneading method. Tablets each containing 50 mg of efavirenz were prepared by wet granulation and direct compression methods employing various HPβCD complexes as per 23 factorial design and the tablets were evaluated for dissolution rate and other physical properties. Efavirenz tablets formulated employing dug-HPβCD-PVP K30/ SLS inclusion complexes and prepared by direct compression method disintegrated rapidly when compared to those made by wet granulation method. Efavirenz dissolution was rapid and higher from the tablets formulated employing drug- HPβCD- PVP K30 /or SLS inclusion complexes when compared to the tablets containing efavirenz alone in both wet granulation and direct compression methods. The individual as well as combined effects of the three factors involved i.e., HPβCD (factor A), PVP K30 (factor B) and SLS (factor C) were highly significant (P < 0.01) in enhancing the dissolution rate (K1) and dissolution efficiency (DE 30) of efavirenz in both wet granulation and direct compression methods. Among the three factors HPβCD (factor A) gave highest enhancement in the dissolution rate (K1) and dissolution efficiency (DE 30) of efavirenz tablets in both wet granulation and direct compression methods. SLS (factor C) alone gave low dissolution rate in both wet granulation and direct compression methods. Overall direct compression method gave higher dissolution rates (K1) and dissolution efficiency (DE 30) values than the wet granulation method in all the cases. Combination of HPβCD with either PVP K30 or SLS or both gave a significantly higher dissolution rate (K1) of efavirenz in both wet granulation and direct compression methods. Hence a combination of HPβCD with either PVP K30 or SLS or both is recommended to enhance the dissolution rate and efficiency of efavirenz tablets.