title: Prilling of fatty acids as a continuous process for the development of controlled release multiparticulate dosage forms.
abstract: In this study, prilling was evaluated as a technique for the development of multiparticulate dosage forms using the fatty acids, stearic acid, and behenic acid as potential matrix formers to control the release of metoprolol tartrate (MPT), a highly water soluble drug. The in vitro drug release was dependent on the drug load, type of fatty acid, and pH of the dissolution medium. Higher drug loads resulted in faster release with behenic acid releasing drug over longer periods relative to stearic acid. The in vitro drug release was pH-dependent at low drug load with the release being slower at lower pH. Due to ionization of the fatty acid at pH 7.4, drug release was susceptible to the ionic strength at this pH value. Solid state characterization indicated that the crystalline state of the fatty acids was not affected by thermal processing via prilling, while the crystallinity of MPT was decreased. During storage, the amorphous MPT fraction recrystallized in the entire matrix. Drug release from behenic acid matrices was increased during storage at 40 °C; however, no polymorphism of behenic acid was detected. The bioavailability of MPT, after oral administration to dogs as prills containing 30% and 40% MPT using behenic acid as matrix former, was not significantly different from a commercial sustained release reference formulation, although the 40% MPT prills showed a burst release.
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium. Electronic address: Chris.Vervaet@UGent.be.
authors.forename: A
authors.initials: A
authors.lastname: Vervaeck
authors.forename: L
authors.initials: L
authors.lastname: Saerens
authors.forename: B G
authors.initials: BG
authors.lastname: De Geest
authors.forename: T
authors.initials: T
authors.lastname: De Beer
authors.forename: R
authors.initials: R
authors.lastname: Carleer
authors.forename: P
authors.initials: P
authors.lastname: Adriaensens
authors.forename: J P
authors.initials: JP
authors.lastname: Remon
authors.forename: C
authors.initials: C
authors.lastname: Vervaet
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D003460:Crystallization; D003692:Delayed-Action Preparations; D004285:Dogs; D004339:Drug Compounding; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry*; D005227:Fatty Acids / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility; D013229:Stearic Acids / Q000737:chemistry*; D013696:Temperature
chemical_list: D003692:Delayed-Action Preparations; D005079:Excipients; D005227:Fatty Acids; D013229:Stearic Acids; C031183:stearic acid; D008790:Metoprolol; C007547:behenic acid
keywords: Controlled release; Fatty acids; Metoprolol tartrate; Multiparticulate dosage forms; Prilling; Stability