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

Abstract

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 –βCD– Poloxamer 407 /PVP K30 inclusion complexes into tablets and to evaluate the effects of βCD, Poloxamer 407 and PVP K30 on the dissolution rate and dissolution efficiency of efavirenz tablets in 23 factorial study. Drug – βCD- Poloxamer 407 / PVP K30 inclusion complexes were prepared by kneading method. Tablets each containing 100 mg of efavirenz were prepared by wet granulation method employing various βCD complexes as per 23 factorial design and the tablets were evaluated for dissolution rate and other physical properties. Efavirenz – βCD– Poloxamer 407 and efavirenz –βCD –PVP K30 inclusion complexes could be formulated into compressed tablets by wet granulation method. Efavirenz dissolution was rapid and higher from the tablets formulated employing drug- βCD- Poloxamer 407/ PVP K30 inclusion complexes when compared to the tablets containing efavirenz alone. The tablets formulated employing drug- βCD- Poloxamer 407/ PVP K30 inclusion complexes fulfilled the official (I.P 2010) dissolution rate test specification of NLT 70 % in 30 min prescribed for efavirenz tablets.The individual as well as combined effects of the three factors involved i.e., βCD ( 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. Among the three factors Poloxamer 407 (factor B) gave highest enhancement in the dissolution rate (K1) and dissolution efficiency (DE 30) of efavirenz tablets. βCD alone gave low dissolution rates. Combination of βCD with Poloxamer 407 or PVP K30 gave a significantly higher dissolution rate (K1) of efavirenz. Hence Poloxamer 407 alone or a combination of βCD with either Poloxamer 407 or PVP K30 is recommended to enhance the dissolution rate and efficiency of efavirenz tablets.