title: In vitro-in vivo correlation strategy applied to an immediate-release solid oral dosage form with a biopharmaceutical classification system IV compound case study.
abstract: The ability to predict in vivo response of an oral dosage form based on an in vitro technique has been a sought after goal of the pharmaceutical scientist. Dissolution testing that demonstrates discrimination to various critical formulations or process attributes provides a sensitive quality check that may be representative or may be overpredictive of potential in vivo changes. Dissolution methodology with an established in vitro-in vivo relationship or correlation may provide the desired in vivo predictability. To establish this in vitro-in vivo link, a clinical study must be performed. In this article, recommendations are given in the selection of batches for the clinical study followed by potential outcome scenarios. The investigation of a Level C in vitro-in vivo correlation (IVIVC), which is the most common correlation for immediate-release oral dosage forms, is presented. Lastly, an IVIVC case study involving a biopharmaceutical classification system class IV compound is presented encompassing this strategy and techniques.
authors.affiliation: Pharmaceutical Sciences and Clinical Supply, Preformulation, Merck, Summit, New Jersey. Electronic address: gerard.bredael@merck.com.
authors.forename: Gerard M
authors.initials: GM
authors.lastname: Bredael
authors.affiliation: Formerly from Analytical Chemistry in Development and Supply, ADC-API and PAT, Merck, Rahway, New Jersey.
authors.forename: Niya
authors.initials: N
authors.lastname: Bowers
authors.affiliation: Pharmaceutical Sciences and Clinical Supply, Analytical Sciences, Merck, Summit, New Jersey.
authors.forename: Fabien
authors.initials: F
authors.lastname: Boulineau
authors.affiliation: Formerly from Pharmaceutical Sciences and Clinical Supply, Analytical Sciences, Merck, Summit, New Jersey.
authors.forename: David
authors.initials: D
authors.lastname: Hahn
mesh_terms: D000284:Administration, Oral; D001702:Biopharmaceutics / Q000379:methods*; D004304:Dosage Forms; D065546:Drug Liberation; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000145:classification* / Q000378:metabolism*; D010599:Pharmacokinetics; D016032:Randomized Controlled Trials as Topic; D012995:Solubility
chemical_list: D004304:Dosage Forms; D004364:Pharmaceutical Preparations
keywords: dissolution; in vitro models; in vitro/in vivo correlations (IVIVC); mathematical models; oral drug delivery