title: Trends in the Assessment of Drug Supersaturation and Precipitation In Vitro Using Lipid-Based Delivery Systems.
abstract: The generation of drug supersaturation close to the absorptive site is an important mechanism of how several formulation technologies enhance oral absorption and bioavailability. Lipid-based formulations belong to the supersaturating drug delivery systems although this is not the only mechanism of how drug absorption is promoted in vivo. Different methods to determine drug supersaturation and precipitation from lipid-based formulations are described in the literature. Experimental in vitro setups vary according to their complexity and proximity to the in vivo conditions and, therefore, some tests are used for early formulation screening, while others better qualify for a later stage of development. The present commentary discusses this rapidly evolving field of in vitro testing with a special focus on the advancements in analytical techniques and new approaches of mechanistic modeling. The importance of considering a drug absorption sink is particularly emphasized. This commentary should help formulators in the pharmaceutical industry as well as in academia to make informed decisions on how to conduct in vitro tests for lipid-based delivery systems and to decide on the implications of experimental results.
authors.affiliation: Pharmaceutical R&D, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Cordula
authors.initials: C
authors.lastname: Stillhart
authors.affiliation: Institute of Pharma Technology, University of Applied Sciences and Arts Northwestern Switzerland, Muttenz, Switzerland. Electronic address: martin.kuentz@fhnw.ch.
authors.forename: Martin
authors.initials: M
authors.lastname: Kuentz
mesh_terms: D001682:Biological Availability; D011232:Chemical Precipitation; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation / Q000639:trends*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006801:Humans; D007408:Intestinal Absorption; D008055:Lipids / Q000737:chemistry*; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D010599:Pharmacokinetics; D012995:Solubility
chemical_list: D004337:Drug Carriers; D008055:Lipids; D004364:Pharmaceutical Preparations
keywords: absorption; bioavailability; lipids; mathematical model; supersaturation