title: Statistical Considerations Concerning Dissimilar Regulatory Requirements for Dissolution Similarity Assessment. The Example of Immediate-Release Dosage Forms.
abstract: When performing in vitro dissolution testing, especially in the area of biowaivers, it is necessary to follow regulatory guidelines to minimize the risk of an unsafe or ineffective product being approved. The present study examines model-independent and model-dependent methods of comparing dissolution profiles based on various compared and contrasted international guidelines. Dissolution profiles for immediate release solid oral dosage forms were generated. The test material comprised tablets containing several substances, with at least 85% of the labeled amount dissolved within 15 min, 20-30 min, or 45 min. Dissolution profile similarity can vary with regard to the following criteria: time point selection (including the last time point), coefficient of variation, and statistical method selection. Variation between regulatory guidance and statistical methods can raise methodological questions and result potentially in a different outcome when reporting dissolution profile testing. The harmonization of existing guidelines would address existing problems concerning the interpretation of regulatory recommendations and research findings.
authors.affiliation: Department of Biopharmacy, Medical University of Łódź, 1 Muszyńskiego Street, 90-151 Lodz, Poland. Electronic address: magdalena.jasinska-stroschein@umed.lodz.pl.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Jasińska-Stroschein
authors.affiliation: Department of Biopharmacy, Medical University of Łódź, 1 Muszyńskiego Street, 90-151 Lodz, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Kurczewska
authors.affiliation: Department of Biopharmacy, Medical University of Łódź, 1 Muszyńskiego Street, 90-151 Lodz, Poland.
authors.forename: Daria
authors.initials: D
authors.lastname: Orszulak-Michalak
mesh_terms: D004304:Dosage Forms; D065546:Drug Liberation / Q000502:physiology; D004335:Drug and Narcotic Control / Q000379:methods / Q000706:statistics & numerical data*; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility
chemical_list: D004304:Dosage Forms; D004364:Pharmaceutical Preparations
keywords: dissolution study; immediate-release dosage forms; regulatory requirements; similarity of profiles; statistical methods