Influence of the preparation method on the physicochemical properties of binary systems of econazole with cyclodextrins.
Equimolar combinations of econazole, a very poorly water soluble antifungal agent, with beta-cyclodextrin and statistically substituted methyl-beta-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-beta-cyclodextrin, whereas crystalline drug was still clearly detectable in all products with beta-cyclodextrin. Independently of the preparation technique, all combinations with methyl-beta-cyclodextrin yielded better performance than the corresponding ones with beta-cyclodextrin. However, the influence of the preparation method was clearly more marked for products with methyl-beta-cyclodextrin and made to be possible to better display the different performance of the examined carriers. In fact, the sealed-heated with the beta-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 beta-cyclodextrin. Moreover, whereas the difference in dissolution efficiency values between coground products was only about 8% in favor of the beta-derivative, it reached 80 and 90% between sealed-heated and kneaded products, respectively.
Mura
P
P
Dipartimento di Scienze Farmaceutiche, Università di Firenze, Via G. Capponi 9, I-50121, Florence, Italy. mura@farmfi.scifarm.unifi.it
Faucci
M T
MT
Manderioli
A
A
Bramanti
G
G
D000935:Antifungal Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003505:Cyclodextrins / Q000737:chemistry*; D004464:Econazole / Q000737:chemistry*; D008853:Microscopy; D012995:Solubility; D013696:Temperature; D013997:Time Factors; D047392:beta-Cyclodextrins
D000935:Antifungal Agents; D003505:Cyclodextrins; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D004464:Econazole; C031215:betadex