A FACTORIAL STUDY ON ENHANCEMENT OF SOLUBILITY AND DISSOLUTION RATE OF ETORICOXIB EMPLOYING β-CYCLODEXTRIN AND SURFACTANTS

Etoricoxib, a widely prescribed anti-inflammatory and analgesic drug belongs to class II under BCS and exhibit low and variable oral bioavailability due to its poor aqueous solubility. It is practically insoluble in water and aqueous fluids. As such its oral absorption is dissolution rate limited and it requires enhancement in 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 employing β-cyclodextrin (βCD) and two surfactants (SLS and Tween 80) alone and in combination. The individual main effects and combined (interaction) effects of β-cyclodextrin and surfactants on the solubility and dissolution rate of etoricoxib were evaluated in a series of 22factorial experiments. The solubility of etoricoxib in the four selected fluids as per 22factorial study in each case was determined (n=4). Etoricoxib-βCD-surfactant inclusion complexes were prepared employing the selected combinations of βCD and surfactant in each case as per a 22 factorial design and the inclusion complexes prepared were evaluated for dissolution rate and dissolution efficiency.Combination of βCD with surfactants, SLS and Tween 80 has resulted in a much higher enhancement in the solubility of etoricoxib than is possible with them individually. ANOVA indicated that the individual main effects of βCD, SLS and Tween 80 as well as the combined effects in enhancing the solubility and dissolution rate of etoricoxib are highly significant (P<0.01). βCD alone gave 1.57 fold increase in the solubility of etoricoxib. Whereas in combination with SLS and Tween 80 it gave respectively 28.97 and 10.54 fold increase in the solubility of etoricoxib. Etoricoxib-βCD and etoricoxib-βCD-Surfactant complexes gave rapid and higher dissolution of etoricoxib when compared to etoricoxib pure drug. βCD alone gave an increase of 10.45 fold in the dissolution rate ( K1 ) of etoricoxib. Combination of βCD with SLS and Tween 80 has given a much higher enhancement in the dissolution rate (K1) of etoricoxib,13.03 and 10.58 folds respectively. Hence, a combination of βCD with surfactants (SLS and Tween 80) is recommended for enhancing the solubility and dissolution rate of etoricoxib , a poorly soluble BCS Class II drug.