Diclofenac/beta-cyclodextrin binary systems: a study in solution and in the solid state

This study was carried out with the aim to optimize the dissoln. properties of diclofenac (DIC) - a non-steroidal anti-inflammatory drug sparingly sol. in water - through assocn. with beta-cyclodextrin (betaCD). The effect of betaCD on the aq. soly. of DIC was evaluated by the phase soly. method. The amt. of DIC dissolved increased linearly with the addn. of betaCD according to an AL type plot and without pptn. of the complex. The apparent stability const. of the complex, calcd. supposing a 1:1 stoichiometry, was 295 M-1; this value was confirmed by CD anal. DIC/betaCD interactions were also studied in water by 1H and 13C NMR spectroscopy. Equimolar DIC/betaCD solid systems were prepd. by phys.-mixing, kneading, co-evapn. and freeze drying, and their properties in the solid state studied by differential scanning calorimetry, x-ray powder diffractometry and Fourier-Transform IR anal. For sake of comparison, the mixt. of DIC and betaCD sep. 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 dissoln. profiles of the drug from each solid system were affected by its physico-chem. properties, the freeze-dried being the most rapidly dissolving forms.