Influence of the preparation method on the physicochemical properties of ketoprofen-cyclodextrin binary systems.
Binary systems of ketoprofen with native crystalline beta-cyclodextrin and amorphous statistically substituted methyl-beta-cyclodextrin were investigated for both solid phase characterization (Differential Scanning Calorimetry, powder X-ray diffraction, Infrared Spectroscopy, Scanning Electron Microscopy) and dissolution properties (dispersed amount and rotating disc methods). Grinding, kneading, sealed-heating and colyophilization of equimolar combinations of ketoprofen with methyl-beta-cyclodextrin, as well as colyophilization of analogous combinations with beta-cyclodextrin, led to amorphous products. Crystalline drug, instead, was still clearly detectable in coground, kneaded and sealed-heated products with beta-cyclodextrin. Both the preparation method, and even more the nature of the carrier, played an important role in the performance of the system. Colyophilized and sealed-heated products showed the best dissolution properties. However, independently of the preparation technique, all combinations with methyl-beta-cyclodextrin yield better performances than the corresponding ones with the beta-cyclodextrin. Moreover, intrinsic dissolution rate of ketoprofen from simple physical mixture with the beta-cyclodextrin derivative was even five-fold higher than that from the best product with the parent beta-cyclodextrin.
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 / Q000008:administration & dosage / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003505:Cyclodextrins / Q000737:chemistry*; D004337:Drug Carriers; D004339:Drug Compounding; D005079:Excipients; D007660:Ketoprofen / Q000008:administration & dosage / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D012995:Solubility; D014961:X-Ray Diffraction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003505:Cyclodextrins; D004337:Drug Carriers; D005079:Excipients; D007660:Ketoprofen