title: Novel insights into excipient effects on the biopharmaceutics of APIs from different BCS classes: Lactose in solid oral dosage forms.
abstract: Excipients encompass a wide range of properties that are of importance for the resulting drug product. Regulatory guidelines on biowaivers for immediate release formulations require an in depth understanding of the biopharmaceutic effects of excipients in order to establish bioequivalence between two different products carrying the same API based on dissolution tests alone. This paper describes a new approach in evaluating biopharmaceutic excipient effects. Actually used quantities of a model excipient, lactose, formulated in combination with APIs from different BCS classes were evaluated. The results suggest that companies use different (relative) amounts depending on the characteristics of the API. The probability of bioinequivalence due to a difference in lactose content between test and reference products was classified as low for BCS class I APIs and medium for BCS class II and III APIs, whereas a high probability was assigned to the combination of lactose and BCS class IV APIs. If repeated for other excipients, this retrospective, top-down approach may lead to a new database and more widespread applications of the biowaiver approach.
authors.affiliation: National Institute for Public Health and the Environment, Bilthoven, The Netherlands; Pharmaceutical Technology and Biopharmaceutics, Johannes Gutenberg University Mainz, Mainz, Germany; Medicines Evaluation Board, Utrecht, The Netherlands.
authors.forename: Marlies
authors.initials: M
authors.lastname: Kubbinga
authors.affiliation: Pharmaceutical Technology and Biopharmaceutics, Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Moghani
authors.affiliation: Pharmaceutical Technology and Biopharmaceutics, Johannes Gutenberg University Mainz, Mainz, Germany. Electronic address: langguth@uni-mainz.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Langguth
mesh_terms: D000284:Administration, Oral; D001702:Biopharmaceutics / Q000145:classification*; D004339:Drug Compounding; D005079:Excipients / Q000494:pharmacology*; D006801:Humans; D007785:Lactose / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D005079:Excipients; D007785:Lactose
keywords: Biopharmaceutic classification system; Biopharmaceutic excipient classification; Biowaiver; Lactose; Pharmaceutical quality attributes; Quality by design