A unifying approach to drug-in-polymer solubility prediction: Streamlining experimental workflow and analysis

IF 4.4 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Bjarke Strøm Larsen , Peter Meiland , Eidan Tzdaka , Ingunn Tho , Thomas Rades
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引用次数: 0

Abstract

This method paper describes currently used experimental methods to predict the drug-in-polymer solubility of amorphous solid dispersions and offers a combined approach for applying the Melting-point-depression method, the Recrystallization method, and the Melting-and-mixing method. It aims to describe and expand on the theoretical basis as well as the analytical methodology of the recently published Melting-and-mixing method. This solubility method relies on determining the relationship between drug loads and the enthalpy of melting and mixing of a crystalline drug in the presence of an amorphous polymer. This relationship is used to determine the soluble drug load of an amorphous solid dispersion from the recorded enthalpy of melting and mixing of the crystalline drug portion in a drug-polymer sample at equilibrium solubility. Due to the complex analytical methodology of the Melting-and-mixing method, a software solution called the Glass Solution Companion app was developed. Using this new tool, it is possible to calculate the predicted drug-in-polymer solubility and Flory-Huggins interaction parameter from experimental samples, as well as to generate the resulting solubility-temperature curve. This software can be used for calculations for all three experimental methods, which would be useful for comparing the applicability of the methods on a given drug-polymer system. Since it is difficult to predict the suitability of these drug-in-polymer solubility methods for a specific drug-polymer system in silico, some experimental investigation is necessary. By optimizing the experimental protocol, it is possible to collect data for the three experimental methods simultaneously for a specific drug-polymer system. These results can then be readily analyzed using the Glass Solution Companion app to find the most appropriate method for the drug-polymer system, and therefore, the most reliable drug-in-polymer solubility prediction.

Abstract Image

药物在聚合物中溶解度预测的统一方法:简化实验工作流程和分析。
本方法论文介绍了目前用于预测无定形固体分散体的药物在聚合物中溶解度的实验方法,并提供了一种综合应用熔点降低法、再结晶法和熔融混合法的方法。它旨在描述和扩展最近发表的熔融混合法的理论基础和分析方法。这种溶解度方法依赖于确定药物载量与结晶药物在无定形聚合物存在下的熔融混合焓之间的关系。这种关系用于根据记录的药物-聚合物样品中晶体药物部分在平衡溶解度下的熔化和混合焓来确定无定形固体分散体的可溶性药物载量。由于熔融混合法的分析方法比较复杂,因此开发了一种名为 Glass Solution Companion 应用程序的软件解决方案。使用这一新工具,可以根据实验样品计算出预测的药物在聚合物中的溶解度和 Flory-Huggins 相互作用参数,并生成溶解度-温度曲线。该软件可用于所有三种实验方法的计算,有助于比较各种方法在特定药物-聚合物体系中的适用性。由于很难在硅学中预测这些药物在聚合物中的溶解度方法是否适用于特定的药物-聚合物体系,因此有必要进行一些实验研究。通过优化实验方案,可以针对特定的药物-聚合物体系同时收集三种实验方法的数据。然后就可以使用 Glass Solution Companion 应用程序对这些结果进行分析,找出最适合药物-聚合物体系的方法,从而得出最可靠的药物-聚合物溶解度预测结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
8.80
自引率
4.10%
发文量
211
审稿时长
36 days
期刊介绍: The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics. Topics covered include for example: Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids) Aspects of manufacturing process design Biomedical aspects of drug product design Strategies and formulations for controlled drug transport across biological barriers Physicochemical aspects of drug product development Novel excipients for drug product design Drug delivery and controlled release systems for systemic and local applications Nanomaterials for therapeutic and diagnostic purposes Advanced therapy medicinal products Medical devices supporting a distinct pharmacological effect.
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