Bustamante Pilar, Navarro-Lupión Javier, Escalera Begoña
Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Alcalá, Alcalá de Henares, E-28871 Madrid, Spain.
Eur J Pharm Sci. 2005 Feb;24(2-3):229-37. doi: 10.1016/j.ejps.2004.10.012.
A modification of the extended Hansen method, formerly used to determine the partial solubility parameters of drugs and non-polymeric excipients is tested with a polymer for the first time. The proposed method relates the logarithm of the intrinsic viscosities of the polymer in a series of solvents and solvent mixtures with the Hansen (three parameter model) and Karger (four parameter model) partial solubility parameters. The viscosity of diluted solutions of hydroxypropyl methylcellulose (HPMC) was determined in pure solvents and binary mixtures of varying polarity. The intrinsic viscosity was obtained from the common intercept of the Huggins and Kraemer relationships. The intrinsic viscosity tends to increase with increasing the solubility parameter of the medium. The results show that hydrogen bonding and polarity of the polymer largely determine polymer-solvent interactions. The models proposed provided reasonable partial and total solubility parameters for the polymer and enable one to quantitatively characterize, for the first time, the Lewis acid-base ability of a polymer thus, providing a more realistic picture of hydrogen bonding for solvent selection/compatibility and to predict drug-polymer interactions. Combination of the dispersion and polar parameters into a single non-specific solubility parameter was also tested. The results extend earlier findings and suggest that the models are quite versatile and may be applied to drugs, non-polymeric and polymeric excipients.
一种曾用于测定药物和非聚合辅料的部分溶解度参数的扩展汉森方法的改进方法,首次用于一种聚合物进行测试。所提出的方法将聚合物在一系列溶剂和溶剂混合物中的特性粘度对数与汉森(三参数模型)和卡尔格(四参数模型)部分溶解度参数相关联。测定了羟丙基甲基纤维素(HPMC)在纯溶剂和不同极性的二元混合物中的稀释溶液的粘度。特性粘度由哈金斯和克雷默关系的共同截距得到。特性粘度倾向于随着介质溶解度参数的增加而增加。结果表明,聚合物的氢键作用和极性在很大程度上决定了聚合物 - 溶剂相互作用。所提出的模型为该聚合物提供了合理的部分和总溶解度参数,并首次能够定量表征聚合物的路易斯酸碱能力,从而为溶剂选择/相容性提供更真实的氢键作用情况,并预测药物 - 聚合物相互作用。还测试了将色散和极性参数组合成单个非特异性溶解度参数的情况。结果扩展了早期的发现,并表明这些模型具有相当的通用性,可应用于药物、非聚合和聚合辅料。