Diclofenac/β-cyclodextrin binary systems:: A study in solution and in the solid state

This study was carried out with the aim to optimize the dissolution properties of diclofenac (DIC) - a non-steroidal antiinflammatory drug sparingly soluble in water - through association with beta-cyclodextrin (betaCD). The effect of betaCD on the aqueous solubility of DIC was evaluated by the phase solubility method. The amount of DIC dissolved increased linearly with the addition of betaCD according to an Al type plot and without precipitation of the complex. The apparent stability constant of the complex, calculated supposing a 1: 1 stoichiometry, was 295 M-1; this value was confirmed by circular dichroism analysis. DIC/betaCD interactions were also studied in water by H-1 and C-13 NMR spectroscopy. Equimolar DIC/betaCD solid systems were prepared by physical-mixing, kneading, co-evaporation and freeze-drying, and their properties in the solid state studied by Differential Scanning Calorimetry, X-ray powder diffractometry and Fourier-Transform Infrared analysis. For sake of comparison, the mixture of DIC and betaCD separately lyophilized was investigated too. The results demonstrated that the freeze-dried product had the highest degree of amorphization and they were in agreement with the existence of an inclusion complex in the solid state. The dissolution profiles of the drug from each solid system were affected by its physico-chemical properties, the freeze-dried being the most rapidly dissolving form.