Characterization of physicochemical properties of naproxen systems with amorphous beta-cyclodextrin-epichlorohydrin polymers.
Ground mixtures of naproxen with amorphous beta-cyclodextrin-epichlorohydrin soluble (betaCd-EPS) or insoluble cross-linked (betaCd-EPI) polymers were investigated for both solid phase characterization (Differential Scanning Calorimetry, powder X-ray Diffractometry) and dissolution properties (dispersed amount method). The effect of different grinding conditions and of drug-to-carrier ratio was also evaluated. Co-grinding induced a decrease in drug crystallinity to an extent which depended on the grinding time, and was most pronounced for the cross-linked insoluble polymer, particularly in combinations at the lowest drug content. Both cyclodextrin polymers were more effective in improving the naproxen dissolution properties, not only than the parent betaCd but also than hydroxyalkyl-derivatives, and their performance was almost comparable to that of methyl-derivatives, previously found as the best carriers for naproxen. Dissolution efficiencies of naproxen from physical mixtures with betaCd-EPS, thanks to the high water solubility of this Cd-derivative, were up to three times higher than those from the corresponding products with betaCd-EPI. However this difference in their performance became much less evident in co-ground products and tended to progressively diminish with increasing the polymer content in the mixture, according to the better amorphizing power shown by betaCd-EPI during the co-grinding process. The 10/90 (w/w) drug-carrier co-ground products exhibited the best dissolution properties, giving dissolution efficiencies about 30 times higher than that of naproxen alone.
Dipartimento di Scienze Farmaceutiche, Università di Firenze, Via G. Capponi 9, Firenze, Italy. mura@farmfi.scifarm.unifi.it
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D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002942:Circular Dichroism; D003505:Cyclodextrins / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D004811:Epichlorohydrin / Q000737:chemistry*; D009288:Naproxen / Q000737:chemistry*; D011108:Polymers; D012995:Solubility; D012996:Solutions; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003505:Cyclodextrins; D004337:Drug Carriers; D011108:Polymers; D012996:Solutions; D047392:beta-Cyclodextrins; D004811:Epichlorohydrin; D009288:Naproxen; C031215:betadex