Abstract

ENHANCEMENT OF SOLUBILITY AND DISSOLUTION RATE OF ETORICOXIB BY HYDROXY PROPYL ? CYCLODEXTRIN AND SOLUTOL HS15 BY 22 FACTORIAL DESIGNS

Lingaraj S. Danki* and G.V. Suresh Kumar

ABSTRACT

Etoricoxib, a widely prescribed anti-inflammatory drug belongs to class IΙ under BCS and exhibit low and variable oral bioavailability due to its poor aqueous solubility. It is practically in soluble in water and aqueous fluids. As such 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 present study is to enhance the solubility and dissolution rate of etoricoxib by the use of hydroxy propyl β cyclodextrin (HPβCD) and Solutol HS15 (non ionic surfactant). The individual main effects and combined (or interaction) effect of HPβCD (Factor A) and Solutol HS15 (Factor B) in enhancing the solubility and dissolution rate of etoricoxib were evaluated in a 22 factorial study. The solubility of etoricoxib in water and water containing selected combinations of the two factors as per 22 factorial design was determined. The individual and combined effects of HPβCD and Solutol HS15 in enhancing the solubility of etoricoxib were highly significant (P < 0.01). HPβCD and Solutol HS15 alone gave respectively 1.90 and 13.30 fold increase in the solubility of etoricoxib. Combination of HPβCD with Solutol HS15 resulted in a much higher enhancement in the solubility of etoricoxib, 18.78 fold. The individual main and combined (interaction) effects of HPβCD (Factor A) and Solutol HS15 (Factor B) in enhancing the dissolution rate (K1) and dissolution efficiency (DE30) were highly significant (P < 0.01). HPβCD alone gave a 16.21 fold increase in the dissolution rate of (K1) of etoricoxib and in combination with Solutol HS15 it gave a 23.24 fold increase in the dissolution rate (K1) of etoricoxib. Solutol HS15 alone also gave higher enhancement in the dissolution rate (17.10 fold) and dissolution efficiency (3.94 fold) of etoricoxib. Hence a combination of HPβCD and Solutol HS15 or Solutol HS15 alone is recommended to enhance the solubility, dissolution rate and dissolution efficiency of etoricoxib, a poorly soluble BCS class II drug.

Keywords: Etoricoxib, Solubility, Dissolution Rate, Hydroxy Propyl ? Cyclodextrin, Solutol HS15.