Extension of the dissolution-precipitation model for kinetic elucidation of solvent-mediated polymorphic transformations

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• 作者：Paulina Jakubiak ; Franz Schuler ; Rubé ; n Alvarez-Sá ; nchez ; ^{ruben.alvarez_sanchez@roche.com}
• 关键词：Polymorphism ; Crystallization ; Crystal forms ; Transformation ; Kinetic model
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：109
• 期：Complete
• 页码：43-48
• 全文大小：922 K
• 卷排序：109

文摘

Thorough understanding and control of the different crystal forms of a drug product is key for fine chemistry and materials science; it ultimately determines the product’s physicochemical properties and performance. In this work, we extend the application of a mechanistic dissolution-precipitation model to solvent-mediated solid form transformations. To address the relevance of the model, various kinetic solvent-mediated polymorphic transition studies were retrieved from the literature. Our model succeeds in accurately describing the experimental data, shedding light on the molecular steps driving the polymorphic conversion. Given its simplicity and mechanistic character, the model can be viewed as a useful tool to monitor, predict and optimize the solvent-mediated transformations of solid forms.