Mura P, Faucci M T, Parrini P L, Furlanetto S, Pinzauti S
Dipartimento di Scienze Farmaceutiche, Università di Firenze, Via G. Capponi 9, Firenze,
Int J Pharm. 1999 Mar 1;179(1):117-28. doi: 10.1016/s0378-5173(98)00390-1.
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.
对酮洛芬与天然结晶β-环糊精以及无定形统计取代甲基-β-环糊精的二元体系进行了研究，包括固相表征（差示扫描量热法、粉末X射线衍射、红外光谱、扫描电子显微镜）和溶解性能（分散量和旋转圆盘法）。酮洛芬与甲基-β-环糊精等摩尔组合的研磨、捏合、密封加热和冷冻干燥，以及与β-环糊精类似组合的冷冻干燥，均得到无定形产物。相反，在与β-环糊精共研磨、捏合和密封加热的产物中仍能清晰检测到结晶药物。制备方法，尤其是载体的性质，对体系性能起着重要作用。冷冻干燥和密封加热的产物表现出最佳的溶解性能。然而，无论制备技术如何，与甲基-β-环糊精的所有组合都比与β-环糊精的相应组合表现更好。此外，酮洛芬与β-环糊精衍生物简单物理混合物的固有溶解速率甚至比与母体β-环糊精的最佳产物高五倍。
