title: In silico simulation of niacin release from lipid tablets: theoretical predictions and independent experiments.
abstract: A mechanistically realistic mathematical model is presented allowing for the quantification of niacin release from lipid tablets, based on glyceryl dibehenate. The systems were prepared either by direct compression or via hot-melt extrusion/grinding/compression. The model assumptions are based on a thorough physico-chemical characterization of the tablets before and after exposure to the release medium. Importantly, the model allows for the first time for the quantitative prediction of the effects of the composition, dimensions and type of preparation method of the tablets on the resulting niacin release kinetics. These quantitative theoretical model predictions were confirmed by several sets of independent experimental results. Furthermore, in silico simulations revealed the fundamental importance of limited niacin solubility within the lipid tablets: during major parts of the release periods, very steep concentration gradients exist and net vitamin flux is restricted to specific regions within the tablets.
authors.affiliation: University of Lille, College of Pharmacy, 3 Rue du Prof. Laguesse, 59006 Lille, France; INSERM U 1008, Controlled Drug Delivery Systems and Biomaterials, 3 Rue du Prof. Laguesse, 59006 Lille, France.
authors.forename: C
authors.initials: C
authors.lastname: Velghe
authors.affiliation: Gattefosse SAS, 36 Chemin de Genas, CS 70070, 69804 Saint-Priest, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Rosiaux
authors.affiliation: Gattefosse SAS, 36 Chemin de Genas, CS 70070, 69804 Saint-Priest, France.
authors.forename: D
authors.initials: D
authors.lastname: Marchaud
authors.affiliation: University of Lille, College of Pharmacy, 3 Rue du Prof. Laguesse, 59006 Lille, France; INSERM U 1008, Controlled Drug Delivery Systems and Biomaterials, 3 Rue du Prof. Laguesse, 59006 Lille, France. Electronic address: juergen.siepmann@univ-lille2.fr.
authors.forename: J
authors.initials: J
authors.lastname: Siepmann
authors.affiliation: University of Lille, College of Pharmacy, 3 Rue du Prof. Laguesse, 59006 Lille, France; INSERM U 1008, Controlled Drug Delivery Systems and Biomaterials, 3 Rue du Prof. Laguesse, 59006 Lille, France.
authors.forename: F
authors.initials: F
authors.lastname: Siepmann
mesh_terms: D003198:Computer Simulation; D004337:Drug Carriers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008956:Models, Chemical; D009525:Niacin / Q000008:administration & dosage*; D012995:Solubility; D013607:Tablets; D014665:Vasodilator Agents / Q000008:administration & dosage*; D014803:Vitamin B Complex / Q000008:administration & dosage*
chemical_list: D004337:Drug Carriers; D008055:Lipids; D013607:Tablets; D014665:Vasodilator Agents; D014803:Vitamin B Complex; D009525:Niacin
keywords: Diffusion; Glyceryl dibehenate; Lipid; Mathematical modeling; Release mechanism; Tablet