title: The effect of the drying temperature on the properties of wet-extruded calcium stearate pellets: pellet microstructure, drug distribution, solid state and drug dissolution.
abstract: Although drying is widely applied during the manufacturing of solid dosage forms, its potential effect on the product's (key) properties is often underestimated. Hence, the present study addresses drying related modifications of wet-extruded pellets comprising calcium stearate (CaSt, matrix former) and ibuprofen (model drug). After spheronization, the pellets were tray dried at different temperatures. The dried pellets were evaluated regarding their microstructure, the ibuprofen distribution, solid state modifications and the resulting in-vitro dissolution profiles. The ibuprofen distribution profiles along the pellets' cross-sections varied for the different drying conditions. The profiles turned from inhomogeneous to uniform with increasing drying temperature. Temperatures above 20°C yielded solid state modifications, including ibuprofen transition into the amorphous state and the formation of eutectic compositions. As none of the batches exhibited a high specific surface area associated with an open, well-interconnected pore system, the dissolution profiles were a function of the ibuprofen distribution. Differences in the solid state did not contribute to the dissolution behavior, since the CaSt matrix did not swell or dissolve in the dissolution medium. These findings show that drying may considerably affect the final product properties even for moderate drying conditions.
authors.affiliation: Institute for Process and Particle Engineering, Graz University of Technology, Austria; Research Center Pharmaceutical Engineering GmbH, Graz, Austria; Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, University of Graz, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Schrank
authors.affiliation: Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbruecken, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Kann
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Graz, Austria.
authors.forename: E
authors.initials: E
authors.lastname: Saurugger
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Graz, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Hainschitz
authors.affiliation: Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbruecken, Germany; Helmholtz Centre for Infection Research (HZI) and Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Department of Drug Delivery (DDEL), Saarbruecken, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Windbergs
authors.affiliation: Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Glasser
authors.affiliation: Institute for Process and Particle Engineering, Graz University of Technology, Austria; Research Center Pharmaceutical Engineering GmbH, Graz, Austria.
authors.forename: J
authors.initials: J
authors.lastname: Khinast
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Graz, Austria; Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, University of Graz, Austria. Electronic address: eva.roblegg@uni-graz.at.
authors.forename: E
authors.initials: E
authors.lastname: Roblegg
mesh_terms: D003890:Desiccation; D004339:Drug Compounding / Q000379:methods*; D065546:Drug Liberation; D007052:Ibuprofen / Q000737:chemistry*; D012995:Solubility; D013059:Spectrum Analysis, Raman; D013229:Stearic Acids / Q000737:chemistry*; D013499:Surface Properties; D013696:Temperature
chemical_list: D013229:Stearic Acids; C031183:stearic acid; D007052:Ibuprofen
keywords: Differential scanning calorimetry; Extrusion/spheronization; Ibuprofen; Infrared spectroscopy; Raman imaging; Small and wide angle X-ray scattering