Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
Institute of Pharma Technology, University of Applied Sciences and Arts Northwestern Switzerland, Muttenz, Switzerland.
J Pharm Pharmacol. 2019 Apr;71(4):441-463. doi: 10.1111/jphp.12948. Epub 2018 Jul 5.
Solubility parameters have been used for decades in various scientific fields including pharmaceutics. It is, however, still a field of active research both on a conceptual and experimental level. This work addresses the need to review solubility parameter applications in pharmaceutics of poorly water-soluble drugs.
An overview of the different experimental and calculation methods to determine solubility parameters is provided, which covers from classical to modern approaches. In the pharmaceutical field, solubility parameters are primarily used to guide organic solvent selection, cocrystals and salt screening, lipid-based delivery, solid dispersions and nano- or microparticulate drug delivery systems. Solubility parameters have been applied for a quantitative assessment of mixtures, or they are simply used to rank excipients for a given drug.
In particular, partial solubility parameters hold great promise for aiding the development of poorly soluble drug delivery systems. This is particularly true in early-stage development, where compound availability and resources are limited. The experimental determination of solubility parameters has its merits despite being rather labour-intensive because further data can be used to continuously improve in silico predictions. Such improvements will ensure that solubility parameters will also in future guide scientists in finding suitable drug formulations.
溶解度参数在包括药剂学在内的多个科学领域已被应用数十年。然而，在概念和实验层面上，它仍然是一个活跃的研究领域。这项工作旨在回顾溶解度参数在难溶性药物药剂学中的应用。
本文概述了用于确定溶解度参数的不同实验和计算方法，涵盖了从经典到现代的方法。在制药领域，溶解度参数主要用于指导有机溶剂选择、共晶和盐筛选、基于脂质的递药、固体分散体以及纳米或微粒药物递药系统。溶解度参数已被用于定量评估混合物，或者简单地用于为给定药物对赋形剂进行排序。
溶解度参数特别有望用于辅助难溶性药物递药系统的开发。在化合物可用性和资源有限的早期开发阶段尤其如此。尽管实验测定溶解度参数非常繁琐，但具有一定的优点，因为可以进一步使用这些数据来持续改进计算预测。这些改进将确保溶解度参数在未来也能指导科学家找到合适的药物制剂。
