title: Selection of a discriminant and biorelevant in vitro dissolution test for the development of fenofibrate self-emulsifying lipid-based formulations.
abstract: Fenofibrate, a BCS class II compound, has a low bioavailability especially when taken orally on an empty stomach. The challenge to find a new formulation for providing bioavailability, independent of food, is still ongoing. If the development of a suitable oral delivery formulation of BCS class II compounds is a frequent and great challenge to formulation scientists, the in vitro evaluation of these new formulations is also a great challenge. The purpose of this study was therefore to select an in vitro dissolution test that would be useful and as biorelevant as possible for the development of fenofibrate self-emulsifying lipid-based formulations. In this context, three different fenofibrate formulations, for which in vivo data are available in the literature, were tested using different dissolution tests until we found the one that was the most suitable. As part of this approach, we started with the simplest in vitro dissolution tests and progressed to tests that were increasingly more complex. The first tests were different single phase dissolution tests: a test under sink conditions based on the USP monograph, and different tests under non-sink conditions in non-biorelevant and biorelevant media. Given the inconclusive results obtained with these tests, biphasic dissolution systems were then tested: one with USP apparatus type II alone and another which combined USP apparatus types II and IV. This last combined test seemed the most suitable in vitro dissolution test for the development of the future fenofibrate lipid-based formulations we intend to develop in our own laboratory.
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmacy, C.I.R.M., University of Liège, Quartier Hôpital, Avenue Hippocrate 15, 4000 Liège, Belgium. Electronic address: Aude.Pestieau@ulg.ac.be.
authors.forename: Aude
authors.initials: A
authors.lastname: Pestieau
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmacy, C.I.R.M., University of Liège, Quartier Hôpital, Avenue Hippocrate 15, 4000 Liège, Belgium.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Krier
authors.affiliation: Galephar Research Center M/F, Rue du Parc Industriel 39, 6900 Marche-en-Famenne, Belgium.
authors.forename: Adeline
authors.initials: A
authors.lastname: Brouwers
authors.affiliation: Galephar Research Center M/F, Rue du Parc Industriel 39, 6900 Marche-en-Famenne, Belgium.
authors.forename: Bruno
authors.initials: B
authors.lastname: Streel
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmacy, C.I.R.M., University of Liège, Quartier Hôpital, Avenue Hippocrate 15, 4000 Liège, Belgium.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Evrard
mesh_terms: D004339:Drug Compounding; D004655:Emulsions; D005215:Fasting; D011345:Fenofibrate / Q000737:chemistry*; D005750:Gastric Juice / Q000737:chemistry; D000960:Hypolipidemic Agents / Q000737:chemistry*; D007419:Intestinal Secretions / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D012995:Solubility
chemical_list: D004655:Emulsions; D000960:Hypolipidemic Agents; D008055:Lipids; D011345:Fenofibrate
keywords: Biphasic dissolution test; Fenofibrate; In vitro dissolution test; Lipid-based formulation; Supersaturation