Department of Chemical Science and Bernal Institute, University of Limerick, Limerick V94 T9PX, Ireland.
Department of Chemical and Pharmaceutical Sciences, University of Trieste, 34127 Trieste, Italy.
Mol Pharm. 2023 Apr 3;20(4):2009-2016. doi: 10.1021/acs.molpharmaceut.2c00984. Epub 2023 Mar 8.
Praziquantel (PZQ) is a chiral class-II drug, and it is used as a racemate for the treatment of schistosomiasis. The knowledge of several cocrystals with dicarboxylic acids has prompted the realization of solid solutions of PZQ with both enantiomers of malic acid and tartaric acid. Here, the solid form landscape of such a six-component system has been investigated. In the process, two new cocrystals were structural-characterized and three non-stoichiometric, mixed crystal forms identified and isolated. Thermal and solubility analysis indicates a fourfold solubility advantage for the newly prepared solid solutions over the pure drug. In addition, a pharmacokinetic study was conducted in rats, which involved innovative mini-capsules for the oral administration of the solid samples. The available data indicate that the faster dissolution rate of the solid solutions translates in faster absorption of the drug and helps maintain a constant steady-state concentration.
吡喹酮(PZQ)是一种手性 II 类药物,作为一种外消旋体用于治疗血吸虫病。了解几种与二羧酸的共晶促使人们实现了 PZQ 与苹果酸和酒石酸两种对映异构体的固体溶液。在这里,研究了这样一个六组分体系的固体形式景观。在此过程中,对两种新的共晶进行了结构表征,并鉴定和分离了三种非化学计量的、混合的晶体形式。热分析和溶解度分析表明,新制备的固体溶液的溶解度比纯药物高出四倍。此外,还在大鼠中进行了药代动力学研究,涉及用于口服固体样品的创新微型胶囊。现有数据表明,固体溶液更快的溶解速率转化为药物更快的吸收,并有助于维持稳定的稳态浓度。