title: Prilling as manufacturing technique for multiparticulate lipid/PEG fixed-dose combinations.
abstract: This study focused on the evaluation of prilling as a technique for the manufacturing of multiparticulate dosage forms. Prills, providing controlled and immediate drug release, were processed and finally combined in capsules yielding a fixed-dose combination. Metoprolol tartrate (MPT) and hydrochlorothiazide (HCT) were used as controlled and immediate release model drugs, respectively. These drugs were embedded in matrices composed of fatty acids and polyethylene glycol (PEG). In order to tailor drug release from the prills, the type of fatty acid, the PEG molecular weight and the fatty acid/PEG ratio were varied. To provide controlled drug release, MPT was embedded in matrices containing PEG and behenic acid. Using different PEG molecular weights (PEG 4000, 6000 and 10,000), MPT release could be tailored over a wide range. To obtain immediate release, HCT was incorporated in matrices composed of PEG and stearic acid. Since high amounts (at least 60%) of PEG were needed for acceptable immediate release, HCT release was independent on PEG molecular weight. Solid state characterization revealed that MPT crystallinity was decreased, while HCT was molecularly dispersed throughout the matrix. Drug release of both MPT and HCT prills was stable during storage. Compared to a fixed-dose reference, oral co-administration of the MPT and HCT prills to dogs yielded a similar bioavailability for the HCT prills, while the MPT prills resulted in a significant higher bioavailability.
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: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Saerens
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: De Beer
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: D058671:Adrenergic beta-1 Receptor Antagonists / Q000008:administration & dosage; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004232:Diuretics / Q000008:administration & dosage; D004304:Dosage Forms; D005227:Fatty Acids / Q000008:administration & dosage* / Q000737:chemistry; D006852:Hydrochlorothiazide / Q000008:administration & dosage; D066298:In Vitro Techniques; D008790:Metoprolol / Q000008:administration & dosage; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D004232:Diuretics; D004304:Dosage Forms; D005227:Fatty Acids; D006852:Hydrochlorothiazide; D011092:Polyethylene Glycols; D008790:Metoprolol
keywords: Controlled release; Fatty acids; Fixed-dose combination; Immediate release; Multiparticulate dosage forms; Polyethylene glycol; Prilling