许多药物的水溶性差已经成为制药业的主要挑战之一。基于聚合物的无定形固体分散体被认为是克服有限的水溶性和口服吸收问题的主要进步。这种方法的主要缺点是它们可能缺乏必要的稳定性并且在储存时回复为结晶形式。重要的前期发展是,因此,需要产生稳定的无定形制剂。对于无定形固体分散体产品的合理设计,必须全面了解在分子水平上发生的过程。这篇综述试图解决控制此类系统物理化学性质的关键分子和热力学方面。生物制药分类系统简介,固体分散体,玻璃化转变,提供了无定形药物的溶解度优势。这篇综述的目的是权衡目前对固体分散化学的理解,并批判性地回顾理论,技术,和分子方面的固体分散体(非晶化和结晶)和潜在的优势聚合物(稳定和溶解)作为惰性,亲水性,药物载体基质。此外,不同的预配制工具,用于合理选择聚合物,用于制备和表征聚合物无定形固体分散体的最新技术,还讨论了胃介质中的药物过饱和。
Poor water solubility of many drugs has emerged as one of the major challenges in the pharmaceutical world. Polymer-based amorphous solid dispersions have been considered as the major advancement in overcoming limited aqueous solubility and oral absorption issues. The principle drawback of this approach is that they can lack necessary stability and revert to the crystalline form on storage. Significant upfront development is, therefore, required to generate stable amorphous formulations. A thorough understanding of the processes occurring at a molecular level is imperative for the rational design of amorphous solid dispersion products. This
review attempts to address the critical molecular and thermodynamic aspects governing the physicochemical properties of such systems. A brief introduction to Biopharmaceutical Classification System, solid dispersions, glass transition, and solubility advantage of amorphous drugs is provided. The objective of this
review is to weigh the current understanding of solid dispersion chemistry and to critically
review the theoretical, technical, and molecular aspects of solid dispersions (amorphization and crystallization) and potential advantage of polymers (stabilization and solubilization) as inert, hydrophilic, pharmaceutical carrier matrices. In addition, different preformulation tools for the rational selection of polymers, state-of-the-art techniques for preparation and characterization of polymeric amorphous solid dispersions, and drug supersaturation in gastric media are also discussed.