Polymers play an essential role in drug formulation and production of medical devices, implants, and diagnostics. Following drug discovery, an appropriate formulation is selected to enable drug delivery. This task can be exceedingly challenging owing to the large number of potential delivery methods and formulation and process variables that can interact in complex ways. This evolving solubility challenge has inspired an increasing emphasis on the developability of drug candidates in early discovery as well as various advanced drug solubilization strategies. Among the latter, formulation approaches that lead to prolonged drug supersaturation to maximize the driving force for sustained intestinal absorption of an oral product, or to allow sufficient time for injection after reconstitution of a parenteral lyophile formulation, have attracted increasing interest. Although several kinetic and thermodynamic components are involved in stabilizing amorphous dispersions, it is generally assumed that maximum physical stability, defined in terms of inhibition of drug crystallization, requires that the drug and excipient remain intimately mixed. Phase separation of the drug from its excipient may be the first step that ultimately leads to crystallization. We discuss the role of advanced thermodynamics using two examples: ASD and vitamin E-stabilized ultrahigh-molecular weight polyethylene implants.

中文翻译：

---

药物配方聚合物设计的热力学原理。

聚合物在药物配方以及医疗器械，植入物和诊断剂的生产中起着至关重要的作用。发现药物后，选择合适的制剂以使药物能够递送。由于存在大量可能以复杂方式相互作用的潜在输送方法，配方和工艺变量，因此该任务可能会极具挑战性。不断发展的溶解性挑战激发了人们对早期发现中候选药物的可开发性以及各种先进的药物增溶策略的日益重视。在后者中，可导致延长药物过饱和度的制剂方法，可最大程度地提高口服制剂对肠道的持续吸收的驱动力，或在重组肠胃外亲液制剂后留出足够的注射时间，引起了越来越多的兴趣。尽管稳定稳定的无定形分散体涉及几种动力学和热力学成分，但通常认为，根据抑制药物结晶的方法定义的最大物理稳定性要求药物和赋形剂保持紧密混合。药物与赋形剂的相分离可能是最终导致结晶的第一步。我们使用两个示例讨论高级热力学的作用：ASD和维生素E稳定的超高分子量聚乙烯植入物。要求药物和赋形剂保持紧密混合。药物与赋形剂的相分离可能是最终导致结晶的第一步。我们使用两个示例讨论高级热力学的作用：ASD和维生素E稳定的超高分子量聚乙烯植入物。要求药物和赋形剂保持紧密混合。药物与赋形剂的相分离可能是最终导致结晶的第一步。我们使用两个示例讨论高级热力学的作用：ASD和维生素E稳定的超高分子量聚乙烯植入物。