Factorial Study to Evaluate the Individual and Combined Effects of β-Cyclodextrin and Sodium Lauryl Sulfate on the Solubility and Dissolution Rate of Etoricoxib

摘要

The objective of the study is to evaluate the individual main effects and combined (or interaction) effects of β-cyclodextrin and sodium lauryl sulfate, a surfactant on the solubility and dissolution rate of etoricoxib in a series of 2~2 factorial experiments. The solubility of etoricoxib in purified water (1), water containing 5 mM of β-cyclodextrin (a), water containing 2 % sodium lauryl sulfate (b) and water containing 5 mM of β-cyclodextrin and 2 % sodium lauryl sulfate (ab) were determined as per 2~2 factorial design. The individual and combined effects of β-cyelodextrin and sodium lauryl sulfate in enhancing the solubility of etoricoxib were highly significant (p < 0.01). The solubility of etoricoxib was markedly enhanced by β-eyclodextrin (2.25 fold), sodium lauryl sulfate (32.16 fold) individually as well as combinedly by β-cyclodextrin and sodium lauryl sulfate (38.82 fold). Solid inclusion complexes of etoricoxib-β-cyclodextrin were prepared with and without sodium lauryl sulfate as per 2~2 factorial design by kneading method. The dissolution rate of etoricoxib from the β-cyclodextrin complexes prepared was studied in phosphate buffer of pH 7.4 (n = 4). The individual main effects of β-cyclodextrin and sodium lauryl sulfate in enhancing the dissolution rate (Kt) and dissolution efficiency (DE_(30)) were highly significant (p < 0.01). Whereas the combined effect of β-cyclodextrin and sodium lauryl sulfate in enhancing the K1 and DE_(30) was not significant (p > 0.05). A 2.90 and 3.15 fold increase in K1 and 4.09 and 2.91 fold increase in DE_(30) of etoricoxib was observed, respectively with β-cyclodextrin and sodium lauryl sulfate.