title: Downstream drug product processing of itraconazole nanosuspension: Factors influencing drug particle size and dissolution from nanosuspension-layered beads.
abstract: There is more research required to broaden the knowledge on the downstream processing of nanosuspensions into solid oral dosage forms, especially for coated nanosuspensions onto beads as carriers. This study focuses on bead layering as one approach to solidify nanosuspensions. The aim was to systematically investigate the influence of type of coating polymer (HPMC VLV vs. copovidone), bead material and bead size (sugar vs. MCC, and small vs. large) and coating thickness (50%-150% layering level) on the properties of a dried itraconazole nanosuspension. A stable itraconazole nanosuspension with a mean particle size below 200nm was prepared and a ratio of itraconazole and coating polymer of around 1:1 was identified. XRD and DSC scans revealed that itraconazole remained mostly crystalline after the bead layering process. The fastest dissolution rate was achieved using the small bead size, sugar beads, HPMC VLV as film-forming polymer and lowest layering level, with the best formulation releasing 94.1% (±3.45% SD) within the first 5min. A deterioration of the release profile with increasing layering level was only observed for MCC beads and was more pronounced when copovidone was used as a coating polymer. It was observed that bead layering is a suitable method to process an itraconazole nanosuspension into a solid form without compromising release.
authors.affiliation: Gustav Parmentier GmbH, Eichendorffstr. 37, 60320 Frankfurt am Main, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Parmentier
authors.affiliation: AbbVie Pte Ltd, Research and Development, 9 North Buona Vista Drive, The Metropolis Tower One #19-01, Singapore 138588, Singapore.
authors.forename: En Hui
authors.initials: EH
authors.lastname: Tan
authors.affiliation: AbbVie GmbH & Co. KG, Knollstrasse 50, 67061 Ludwigshafen, Germany. Electronic address: ariana.low@abbvie.com.
authors.forename: Ariana
authors.initials: A
authors.lastname: Low
authors.affiliation: Department of Pharmaceutical Technology, Biotechnology and Quality Management, Free University of Berlin, 14195 Berlin, Germany.
authors.forename: Jan Peter
authors.initials: JP
authors.lastname: Möschwitzer
mesh_terms: D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D017964:Itraconazole / Q000032:analysis*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D012995:Solubility; D013535:Suspensions
chemical_list: D013535:Suspensions; D017964:Itraconazole
keywords: Downstream processing; Formulation; Multiparticulate oral dosage forms; Nano milling; Nanoparticles; Nanosuspensions; Nanotechnology; Pellet layering; Poor solubility; Processing