Abstract：
Salts of weakly basic drugs can partially dissociate in formulations, to give basic drugs and counter acids. The aim of the present study was to clarify the effect of physicochemical properties on the basic drug-acid-polymer interactions and salt-polymer miscibility, and to explain the influence mechanism at the molecular level. Six maleate salts with different physicochemical properties were selected and PVA was used as the film forming material. The relationship between the physicochemical properties and the miscibility was presented with multiple linear regression analysis. The existence state of salts in formulations were determined by XRD and Raman imaging. The stability of salts was characterized by NMR and XPS. The intermolecular interactions were investigated by FTIR and NMR. The results showed that the salt-PVA miscibility was related to polar surface area of salts and Tg of free bases, which represented hydrogen bond interaction and solubility potential. The basic drug-acid-PVA intermolecular interactions determined the existence state and bonding pattern of the three molecules. Meanwhile, the decrease of the stability after formulation increased the number of free bases in orodispersible films, which in turn affected the miscibility with PVA. The study provided references for the rational design of PVA based orodispersible films.
摘要：
弱碱性药物的盐可以在制剂中部分解离，给予基本药物和反酸。本研究的目的是阐明物理化学性质对碱性药物-酸-聚合物相互作用和盐-聚合物混溶性的影响，并从分子水平解释其影响机制。选用6种不同理化性质的马来酸盐,以PVA为成膜材料。用多元线性回归分析了理化性质与混溶性之间的关系。通过XRD和拉曼成像确定制剂中盐的存在状态。通过NMR和XPS表征盐的稳定性。通过FTIR和NMR研究了分子间的相互作用。结果表明，盐与PVA的混溶性与盐的极性表面积和游离碱的Tg有关，代表氢键相互作用和溶解度势。碱性药物-酸-PVA分子间相互作用决定了三个分子的存在状态和键合模式。同时,配制后稳定性的降低增加了口腔分散膜中游离碱的数量，进而影响与PVA的混溶性。该研究为PVA基口腔分散膜的合理设计提供了参考。
