Abstract

FACTORIAL STUDIES ON FORMULATION DEVELOPMENT OF IRBESARTAN TABLETS EMPLOYING ?CD AND KOLLIPHOR HS15

T. Srinivasa Rao and K.P.R. Chowdary*

Abstract

Irbesartan is an effective antihypertensive drug. It belongs to class II under Biopharmaceutical classification system and exhibit low and variable oral bioavailability due to its poor solubility. It is practically insoluble in water and aqueous fluids and its oral absorption is dissolution rate limited. It needs enhancement in solubility and dissolution rate for improvement of its oral bioavailability and therapeutic efficacy. The objective of the present study is to enhance the dissolution rate and formulation development of Irbesartan tablets with fast dissolution characteristics employing βCD and Kolliphor HS15, a non ionic surfactant. The individual and combined effects of βCD (factor A) and Kolliphor HS15 (factor B) on the dissolution rate of Irbesartan from solid inclusion complexes and their tablets were evaluated in a series of 22 factorial experiments. The feasibility of formulating Irbesartan - βCD-Kolliphor HS15 inclusion complexes into tablets with fast dissolution rate characteristics was also investigated. The individual and combined effects of βCD and Kolliphor HS15 in enhancing the dissolution rate and dissolution efficiency of Irbesartan from solid inclusion complexes and their tablets were highly significant (P < 0.01). The dissolution of Irbesartan was rapid and higher in the case of Irbesartan- βCD and Irbesartan- βCD - Kolliphor HS15 complexes prepared when compared to Irbesartan pure drug. β CD alone gave a 8.26 fold increase and in combination with Kolliphor HS15 it gave 9.94 fold increase in the dissolution rate of (K1) of Irbesartan. Irbesartan –βCD – Kolliphor HS15 inclusion complexes could be formulated into compressed tablets by wet granulation method and the resulting tablets also gave rapid and higher dissolution of Irbesartan. Irbesartan tablets formulated with βCD and Kolliphor HS15 individually gave 4.85 and 6.45 fold increase in the dissolution rate and those containing drug - βCD -Kolliphor HS15 complex gave much higher enhancement (22.65 fold) in the dissolution rate when compared to tablets formulated with Irbesartan pure drug. Combination of βCD and Kolliphor HS15 gave much higher enhancement in the dissolution rate of Irbesartan tablets than is possible with them individually. A combination of βCD with Kolliphor HS15 is recommended to enhance the dissolution rate in the formulation development of Irbesartan tablets with fast dissolution rate characteristics.

Keywords: Irbesartan, ? Cyclodextrin, Kolliphor HS15, Dissolution Rate, Irbesartan Tablets, Formulation development.