Abstrakt

Formulation and Evaluation of Valsartan Tablets Employing Cyclodextrin-Poloxamer 407-PVP K30 Inclusion Complexes

K. P. R. Chowdary, K. Surya Prakasa Rao and Amar Ayireddy

Valsartan, a widely prescribed anti-hypertensive 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 valsartan–CD (βCD/ HPβCD)–Poloxamer 407 and valsartan–CD (βCD/ HPβCD) –PVP K30 inclusion complexes into tablets and to evaluate the effects of CDs, Poloxamer 407 and PVP K30 on the dissolution rate of valsartan tablets. A comparative evaluation of wet granulation and direct compression methods was made for the preparation of tablets employing drug–CD–Poloxamer 407/PVP K30 inclusion complexes. Drug–CDPoloxamer 407/PVP K30 inclusion complexes were prepared by kneading method. Tablets each containing 40 mg of valsartan were prepared by wet granulation and direct compression methods employing various CD complexes and the tablets were evaluated for dissolution rate and other physical properties. Valsartan tablets made by direct compression method disintegrated rapidly when compared to those made by wet granulation method. Tablets formulated employing βCD complexes disintegrated relatively more rapidly than those formulated employing HPβCD complexes. Valsartan dissolution was rapid and higher from the tablets formulated employing drug-CD-Poloxamer 407/ PVP K30 inclusion complexes when compared to the tablets containing valsartan alone and drug – CD complexes in both wet granulation and direct compression methods. In both the methods tablets formulated employing βCD complexes gave higher dissolution rates (K1) and DE30 values when compared to those formulated employing HPβCD complexes. Tablets formulated employing dug–βCD–Poloxamer 407 and drug–βCD– PVP K30 complexes and prepared by direct compression method gave higher dissolution rates, 0.0944 and 0.0833 min-1 respectively when compared to plain tablets (0.0326 min-1) as well as tablets containing drug – βCD complexes (0.0641 min-1). Hence a combination of βCD with Poloxamer 407 or PVP K30 is recommended to enhance the dissolution rate of valsartan tablets.