Factorial Study to Evaluate the Individual and Combined Effects of Cyclodextrins and Tween 80 on the Solubility and Dissolution Rate of Aceclofenac

摘要

The objective of the study is to evaluate the individual main effects and combined (or interaction) effects of two cyclodextrins [β-cyclodextrin (βCD) and hydroxypropyl-β-eyclodextrin (HPpCD)] and Tween 80, a surfactant on the solubility and dissolution rate of aceclofenac in a series of 2~2 factorial experiments. The solubility of aceclofenac in purified water (1), water containing 5 mM of cyclodextrins (pCD or HPβCD) (a), water containing 2 % Tween 80 (b) and water containing 5 mM of CDs (βCD or HPpCD) and 2 % Tween 80 (ab) were determined as per 22 factorial design. The individual and combined effects of βCD, HPβCD and Tween 80 in enhancing the solubility of aceclofenac were highly significant (p < 0.01). The solubility of aceclofenac was markedly enhanced by βCD (1.57 fold), HPβCD (1.47 fold), Tween 80 (7.91 fold) individually as well as combindly by βCD-Tween 80 (10.54 fold) HPβCD-Tween 80 (11.96 fold). Solid inclusion complexes of aceclofenac-cyclodextrins (βCD or HPβCD) were prepared with and without Tween 80 as per 2~2 factorial design by kneading method. The dissolution rate of aceclofenac from the cyclodextrin complexes prepared was studied in phosphate buffer of pH 6.8 (n = 4). Cyclodextrins alone gave higher enhancement in the dissolution rate and DE_(15) of aceclofenac. The individual main effect of cyclodextrins (pCD and HPβCD) and the combined effect of cyclodextrins and Tween 80 in enhancing the dissolution rate and DE_(15) were highly significant (p < 0.01). Whereas the main effect of Tween 80 was not significant (p > 0.05), Thus, a combination of βCD-Tween 80 and HPβCD-Tween 80 is recommended for enhancing the solubility and dissolution rate of aceclofenac.