title: In vitro-in vivo correlations: general concepts, methodologies and regulatory applications.
abstract: The major objective of in vitro-in vivo correlations is to be able to use in vitro data to predict in vivo performance serving as a surrogate for an in vivo bioavailability test and to support biowaivers. Therefore, the aims of this review are: (i) to clarify the factors involved during bio-predictive dissolution method development; and (ii) the elements that may affect the mathematical analysis in order to exploit all information available. This article covers the basic aspects of dissolution media and apparatus used in the development of in vivo predictive dissolution methods, including the latest proposals in this field as well as the summary of the mathematical methods for establishing the in vitro-in vivo relationship and their scope and limitations. The incorporation of physiological relevant factors in the in vitro dissolution method is essential to get accurate in vivo predictions. Standard quality control dissolution methods do not necessarily reflect the in vivo behavior, so they rarely are useful for predicting in vivo performance. The combination of physiological based dissolution methods with physiological-based pharmacokinetics models incorporating gastrointestinal variables will lead to robust tools for drug and formulation development, nevertheless their regulatory use for biowaiver application still require harmonization of the mathematical methods proposed and more detailed recommendations about the procedures for setting up dissolution specifications.
authors.affiliation: a Department of Engineering , Area of Pharmaceutics and Pharmaceutical Technology, Miguel Hernández University , Elche , Spain .|b Department of Pharmaceutics and Pharmaceutical Technology , University of Valencia , Valencia , Spain , and.
authors.forename: Ignacio
authors.initials: I
authors.lastname: González-García
authors.affiliation: a Department of Engineering , Area of Pharmaceutics and Pharmaceutical Technology, Miguel Hernández University , Elche , Spain .|b Department of Pharmaceutics and Pharmaceutical Technology , University of Valencia , Valencia , Spain , and.
authors.forename: Victor
authors.initials: V
authors.lastname: Mangas-Sanjuán
authors.affiliation: b Department of Pharmaceutics and Pharmaceutical Technology , University of Valencia , Valencia , Spain , and.|c Centre for Molecular Recognition and Technological Development, Centre of Polytechnic University of Valencia-University of Valencia , Valencia , Spain.
authors.forename: Matilde
authors.initials: M
authors.lastname: Merino-Sanjuán
authors.affiliation: a Department of Engineering , Area of Pharmaceutics and Pharmaceutical Technology, Miguel Hernández University , Elche , Spain .
authors.forename: Marival
authors.initials: M
authors.lastname: Bermejo
mesh_terms: D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000331:legislation & jurisprudence* / Q000639:trends*; D055808:Drug Discovery / Q000331:legislation & jurisprudence* / Q000639:trends*; D006801:Humans; D012995:Solubility
keywords: BCS; EMA; FDA; IVIVC; biorelevant media; biowaiver; dissolution methods; one-stage methods; two-stage methods