Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky 40506.
J Pharm Sci. 2018 Jan;107(1):24-33. doi: 10.1016/j.xphs.2017.09.030. Epub 2017 Oct 12.
The evolving challenges associated with the development of poorly soluble drug molecules have been met with major advances in drug solubilization. In particular, amorphous solid dispersion technology is becoming an increasingly important option to enhance oral bioavailability by creating prolonged drug supersaturation to maximize the driving force for intestinal absorption. A primary concern in the development of amorphous solid dispersions is their physical stability, leading to increasing interest in predictive methodologies to assess the propensity for drug crystallization under various storage conditions. For most drug-excipient combinations of pharmaceutical interest, hydrogen bonding is an important factor in determining miscibility, supersaturation potential, and the influence of water uptake during storage and after administration. The vast majority of publications to date have utilized mathematical models based on regular solution theory such as Flory-Huggins theory to predict drug-polymer miscibility, despite the fact that they were never intended to be applied to hydrogen-bonded systems. In this commentary article, regular solution theory is applied to simple hydrogen-bonded alcohol-alkane solutions to explore trends in the Flory-Huggins χ interaction parameter and possible pitfalls in its interpretation. More recent models that explicitly allow for specific interactions merit greater attention.
发展水溶性差的药物分子所带来的不断变化的挑战，已经在药物增溶方面取得了重大进展。特别是无定形固体分散技术正成为提高口服生物利用度的一种越来越重要的选择，通过创造延长的药物过饱和来最大限度地提高肠道吸收的驱动力。在无定形固体分散体的开发中，一个主要关注点是其物理稳定性，这导致人们越来越关注预测方法，以评估在各种储存条件下药物结晶的倾向。对于大多数具有药物赋形剂组合的药物，氢键是决定混溶性、过饱和度潜力以及在储存和给药后水摄取影响的重要因素。迄今为止，绝大多数出版物都利用基于规则溶液理论（如 Flory-Huggins 理论）的数学模型来预测药物-聚合物的混溶性，尽管它们从未打算应用于氢键系统。在这篇评论文章中，规则溶液理论被应用于简单的氢键醇-烷烃溶液，以探索 Flory-Huggins χ 相互作用参数的趋势和其解释中的可能陷阱。更最近的明确允许特定相互作用的模型值得更多关注。
