A FACTORIAL STUDY ON FORMULATION DEVELOPMENT OF EFAVIRENZ TABLETS EMPLOYING ? CYCLODEXTRIN- POLOXAMER 407- PVP K30

摘要

Efavirenz, a widely prescribed anti retroviral drug belongs to class I|? 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 ¨C|?CD¨C Poloxamer 407 /PVP K30 inclusion complexes into tablets and to evaluate the effects of |?CD, Poloxamer 407 and PVP K30 on the dissolution rate and dissolution efficiency of efavirenz tablets in 23factorial study. A comparative evaluation of wet granulation and direct compression methods was made for the preparation of tablets employing drug ¨C |?CD ¨C Poloxamer 407 / PVP K30 inclusion complexes. Drug ¨C |?CD- Poloxamer 407 / PVP K30 inclusion complex es were prepared by kneading method. Tablets each containing 100 mg of efavirenz were prepared by wet granulation and direct compression methods employing various |?CD complexes as per 23 factorial design and the tablets were evaluated for dissolution rate and other physical properties. Efavirenz tablets formulated employing dug ¨C |?CD ¨C Poloxamer 407 / PVP K30 inclusion complex es 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- |?CD- Poloxamer 407/ PVP K30 inclusion complexes when compared to the tablets containing efavirenz alone in both wet granulation and direc t compression methods. The individual as well as combined effects of the three factors involved i.e., |?CD ( factor A), Poloxamer 407 ( factor B) and PVP K30 ( 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 Poloxamer 407 (factor B) gave highest enhancement in the dissolution rate (K1) and dissolution efficiency (DE 30) of efavirenz tablets in both wet granulation and direct compression methods. |?CD alone gave low dissolution rates in both wet granulation and direct compression methods. Combination of |?CD with Poloxamer 407 or PVP K30 gave a significantly higher dissolution rate (K1) of efavirenz 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. Hence Poloxamer 407 alone or a combination of |?CD with either Poloxamer 407 or PVP K30 is recommended to enhance the dissolution rate and efficiency of efavirenz tablets. Direct compression method was more suitable to prepare efavirenz tablets with rapid disintegration and dissolution characteristics employing drug- |?CD - Poloxamer 407 / PVP K30 inclusion complexes