title: Fatty acids for controlled release applications: A comparison between prilling and solid lipid extrusion as manufacturing techniques.
abstract: The aim of the present study was to evaluate the solid state characteristics, drug release and stability of fatty acid-based formulations after processing via prilling and solid lipid extrusion. Myristic acid (MA), stearic acid (SA) and behenic acid (BA) were used as matrix formers combined with metoprolol tartrate (MPT) as model drug. The prilling process allowed complete dissolution of MPT in the molten fatty acid phase, generating semi-crystalline MPT and the formation of hydrogen bonds between drug and fatty acids in the solid prills. In contrast, as solid lipid extrusion (SLE) induced only limited melting of the fatty acids, molecular interaction with the drug was inhibited, yielding crystalline MPT. Although the addition of a low melting fatty acid allowed more MPT/fatty acid interaction during extrusion, crystalline MPT was detected after processing. Mathematical modeling revealed that the extrudates exhibited a higher apparent drug/water mobility than prills of the same composition, probably due to differences in the inner systems' structure. Irrespective of the processing method, mixed fatty acid systems (e.g. MA/BA) exhibited a lower matrix porosity, resulting in a slower drug release rate. Solid state analysis of these systems indicated that the crystalline structure of the fatty acids was maintained after SLE, while prilling generated a reduced MA crystallinity. Binary MPT/fatty acid systems processed via extrusion showed better stability during storage at 40 °C than the corresponding prills. Although mixed fatty acid systems were stable at 25 °C, stability problems were encountered during storage at 40 °C: a faster release was obtained from the prills, whereas drug release from the extrudates was slower.
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Vervaeck
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: Monteyne
authors.affiliation: INSERM U1008, College of Pharmacy, University of Lille, Lille, France.
authors.forename: F
authors.initials: F
authors.lastname: Siepmann
authors.affiliation: Centre for X-ray Tomography (UGCT), Department of Physics and Astronomy, Ghent University, Ghent, Belgium.
authors.forename: M N
authors.initials: MN
authors.lastname: Boone
authors.affiliation: Centre for X-ray Tomography (UGCT), Department of Physics and Astronomy, Ghent University, Ghent, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Van Hoorebeke
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: De Beer
authors.affiliation: INSERM U1008, College of Pharmacy, University of Lille, Lille, France.
authors.forename: J
authors.initials: J
authors.lastname: Siepmann
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: J P
authors.initials: JP
authors.lastname: Remon
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium. Electronic address: Chris.Vervaet@UGent.be.
authors.forename: C
authors.initials: C
authors.lastname: Vervaet
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003460:Crystallization; D003692:Delayed-Action Preparations; D065546:Drug Liberation; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry*; D005227:Fatty Acids / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry; D008790:Metoprolol / Q000008:administration & dosage* / Q000737:chemistry; D008962:Models, Theoretical; D019814:Myristic Acid / Q000737:chemistry; D016062:Porosity; D012995:Solubility; D013229:Stearic Acids / Q000737:chemistry; D013696:Temperature
chemical_list: D003692:Delayed-Action Preparations; D005079:Excipients; D005227:Fatty Acids; D008055:Lipids; D013229:Stearic Acids; D019814:Myristic Acid; C031183:stearic acid; D008790:Metoprolol; C007547:behenic acid
keywords: Controlled release; Fatty acids; Mathematical modeling; Metoprolol tartrate; PAT; Prilling; Solid lipid extrusion; Stability