Mura Paola, Bettinetti Gian Piero, Cirri Marzia, Maestrelli Francesca, Sorrenti Milena, Catenacci Laura
Dipartimento di Scienze Farmaceutiche, Università di Firenze, Firenze, Italy.
Eur J Pharm Biopharm. 2005 Jan;59(1):99-106. doi: 10.1016/j.ejpb.2004.05.005.
The effect of ternary complexation of naproxen, a poorly water soluble anti-inflammatory drug, with hydroxypropyl-beta-cyclodextrin and the basic aminoacid L-arginine on the drug dissolution properties has been investigated. Equimolar binary (drug-cyclodextrin or drug-arginine) and ternary (drug-cyclodextrin-arginine) systems were prepared by blending, cogrinding, coevaporation, and characterized by differential scanning calorimetry, thermogravimetric analysis, FT-IR spectroscopy, X-ray diffractometry. The dissolution behavior of naproxen from the different products was evaluated by means of a continuous flow through method. The results of solid state studies indicated the presence of strong interactions between the components in ternary coevaporated and coground systems, which were both of totally amorphous nature. In contrast, the presence of either free drug or free arginine was detected when the third component (cyclodextrin or aminoacid) was physically mixed, respectively, to the drug-arginine binary system (as physical mixture, coevaporate, or coground product) or to the drug-cyclodextrin binary system (as physical mixture, coevaporate, or coground product). All ternary combinations were significantly (P<0.001) more effective than the corresponding binary drug-cyclodextrin and drug-arginine systems in improving the naproxen dissolution rate. The best performance in this respect was given by the ternary coevaporate, with about 15 times increase in terms of both drug relative dissolution rate and dissolution efficiency. The synergistic effect of the simultaneous use of arginine and cyclodextrin on the dissolution rate of naproxen was attributed to the combined effects of inclusion in cyclodextrin and salt formation, as well as to a specific role played by arginine in this interaction.
研究了难溶性抗炎药萘普生与羟丙基-β-环糊精和碱性氨基酸L-精氨酸形成的三元络合物对药物溶解性能的影响。通过混合、共研磨、共蒸发制备了等摩尔二元体系（药物-环糊精或药物-精氨酸）和三元体系（药物-环糊精-精氨酸），并通过差示扫描量热法、热重分析、傅里叶变换红外光谱、X射线衍射法对其进行了表征。采用连续流动法评价了萘普生在不同产品中的溶解行为。固态研究结果表明，在三元共蒸发和共研磨体系中各组分之间存在强相互作用，这两种体系均为完全无定形性质。相比之下，当分别将第三种组分（环糊精或氨基酸）与药物-精氨酸二元体系（作为物理混合物、共蒸发产物或共研磨产物）或药物-环糊精二元体系（作为物理混合物、共蒸发产物或共研磨产物）物理混合时，检测到游离药物或游离精氨酸的存在。在提高萘普生溶解速率方面，所有三元组合均显著（P<0.001）优于相应的二元药物-环糊精和药物-精氨酸体系。在这方面表现最佳的是三元共蒸发产物，其药物相对溶解速率和溶解效率均提高了约15倍。精氨酸和环糊精同时使用对萘普生溶解速率的协同作用归因于环糊精包合和盐形成的综合作用，以及精氨酸在这种相互作用中所起的特定作用。
