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A Factorial Study on the Effects of Cyclodextrins, Poloxamer 407 and PVP on the Solubility and Dissolution Rate of Etoricoxib

K. P. R. Chowdary, K. Surya Prakasa Rao and D. Madhuri

The individual main effects and combined (o r interaction) effects of cyclodextrins ( β CD and HP β CD), surfactant (Poloxamer 407) and PVP on the solubility and dissolution rate of etoricoxib were evaluated in a series of 2 3 factorial experiments. The solubility of etoricoxib in eight selected fluids containing CDs, Poloxamer 407 and PVP as per 2 3 factorial study was determined. The solubility of etoricoxib was markedly enhanced by β CD (2.24 fold), HP β CD (3.14 fold), Poloxamer 407 (2.58 fold) and PVP (1.38 fold) individually. β CD in combination with PVP has given highest enhancement (3.44 fold) in the solubility of etoricoxib. HP β CD in combination with Poloxamer 407 and PVP gave respectively 3.74 and 3.39 fold increase in the solubility of etoricoxib. Both the individual and combined effects were highly significant (P < 0.01). Solid inclusion complexes of etoricoxib-CDs ( β CD and HP- β CD) were prepared with and without Poloxamer 407 and PVP by kneading method as per 2 3 -factorial design. ANOVA indicated that the indivi dual main effects of CDs ( β CD and HP- β CD), Poloxamer 407 and PVP and their combined effects in enhancing the dissolution rate (K 1 ) and DE 30 were highly significant (P < 0.01). β CD alone gave a 1.18 fold increase in the dissolution rate of etoricoxib. β CD in combination with PVP and Poloxamer 407 gave respectively 3.0 and 7.4 fold increase in the dissolution rate of etoricoxib. HP β CD alone gave a 3.55 fold increase and in combination with PVP and Poloxamer 407 it gave respectively 57.6 and 23.6 fold increase in the dissolution rate of etoricoxib. Combination of CDs with either Poloxamer 407 or PVP has markedly enhanced bot h the solubility and dissolution rate of etoricoxib, a BCS class II drug.