Veiga M D, Díaz P J, Ahsan F
Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid, Spain.
J Pharm Sci. 1998 Jul;87(7):891-900. doi: 10.1021/js970233x.
Griseofulvin/cyclodextrin interactions were investigated in aqueous environment and in solid state. Two cyclodextrin derivatives (beta-cyclodextrin and 2-hydroxypropyl beta-cyclodextrin) were used to prepare different physical mixtures and kneaded systems, and the drug/cyclodextrin ratios were 1:1 and 1:2 mol/mol. Scanning electron microscopy (SEM), hot-stage microscopy (HSM), differential scanning calorimetry (DSC), thermogravimetry (TG), and X-ray powder diffractometry were employed to characterize pure substances and their kneaded counterparts and all of the binary systems. The solubility of griseofulvin was increased in accord with the quantity of cyclodextrin added. HSM examination revealed that 2-hydroxypropyl-beta-cyclodextrin was dissolved in the droplets of melted griseofulvin, but did not show any interactions between melted griseofulvin and beta-cyclodextrin particles. The presence of griseofulvin endothermic peak in the DSC curves of all binary systems suggests the absence of any griseofulvin/cylcodextrin inclusion compound in the solid state. In TG, data of weight loss owing to the dehydration of cyclodextrins was similar for both kneaded systems and physical mixtures. X-ray diffraction patterns exhibited the amorphous nature of 2-hydroxypropyl-beta-cyclodextrin and the crystalline nature of griseofulvin and binary systems. Griseofulvin dissolution profiles from all binary systems showed an improvement in drug dissolution, which indicates that an "in situ" drug/cyclodextrin inclusion compound was formed in the aqueous dissolution medium.
在水性环境和固态条件下研究了灰黄霉素与环糊精的相互作用。使用两种环糊精衍生物（β-环糊精和2-羟丙基-β-环糊精）制备不同的物理混合物和捏合体系，药物/环糊精的摩尔比为1:1和1:2。采用扫描电子显微镜（SEM）、热台显微镜（HSM）、差示扫描量热法（DSC）、热重分析法（TG）和X射线粉末衍射法对纯物质及其捏合产物以及所有二元体系进行表征。灰黄霉素的溶解度随环糊精添加量的增加而提高。热台显微镜检查显示，2-羟丙基-β-环糊精溶解于熔融的灰黄霉素液滴中，但熔融的灰黄霉素与β-环糊精颗粒之间未显示出任何相互作用。所有二元体系的差示扫描量热曲线中灰黄霉素吸热峰的存在表明固态下不存在任何灰黄霉素/环糊精包合物。在热重分析中，捏合体系和物理混合物中环糊精脱水导致的失重数据相似。X射线衍射图谱显示2-羟丙基-β-环糊精为无定形性质，灰黄霉素和二元体系为结晶性质。所有二元体系的灰黄霉素溶出曲线显示药物溶出有所改善，这表明在水性溶出介质中形成了“原位”药物/环糊精包合物。
