Influence of the preparation method on the physicochemical properties of binary systems of econazole with cyclodextrins

Abstract

Equimolar combinations of econazole, a very poorly water soluble antifungal agent, with β-cyclodextrin and statistically substituted methyl-β-cyclodextrin were investigated for both solid state characterization (differential scanning calorimetry, hot-stage microscopy, infrared spectroscopy, scanning electron microscopy) and dissolution properties (dispersed amount method). The influence of the preparation method (physical mixing, ball-milling, kneading, sealed-heating) on the physicochemical properties of the products was evaluated. Kneading and sealed-heating techniques led to amorphous products in the case of systems with methyl-β-cyclodextrin, whereas crystalline drug was still clearly detectable in all products with β-cyclodextrin. Independently of the preparation technique, all combinations with methyl-β-cyclodextrin yielded better performance than the corresponding ones with β-cyclodextrin. However, the influence of the preparation method was clearly more marked for products with methyl-β-cyclodextrin and made to be possible to better display the different performance of the examined carriers. In fact, the sealed-heated with the β-derivative showed an increase of drug dissolution efficiency of 130% with respect to the corresponding physical mixture, in comparison to the 70% increase obtained from that with β-cyclodextrin. Moreover, whereas the difference in dissolution efficiency values between coground products was only about 8% in favor of the β-derivative, it reached 80 and 90% between sealed-heated and kneaded products, respectively.