title: Extension of the dissolution-precipitation model for kinetic elucidation of solvent-mediated polymorphic transformations.
abstract: 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.
authors.affiliation: Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Switzerland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Jakubiak
authors.affiliation: Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Switzerland.
authors.forename: Franz
authors.initials: F
authors.lastname: Schuler
authors.affiliation: Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Switzerland. Electronic address: ruben.alvarez_sanchez@roche.com.
authors.forename: Rubén
authors.initials: R
authors.lastname: Alvarez-Sánchez
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003460:Crystallization; D004339:Drug Compounding / Q000379:methods*; D000431:Ethanol / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008962:Models, Theoretical; D019438:Ritonavir / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013696:Temperature; D013997:Time Factors
chemical_list: D012997:Solvents; D000431:Ethanol; D019438:Ritonavir
keywords: Crystal forms; Crystallization; Kinetic model; Polymorphism; Transformation