title: Improving the granule strength of roller-compacted ibuprofen sodium for hot-melt coating processing.
abstract: Solvent-free hot-melt coating processing is a novel and cost-efficient approach to manufacturing taste-masked multiparticulate systems. However, most API powders are fine and cohesive and not processable by hot-melt coating. The aim of this study was to produce dense and abrasion-resistant granules with high drug content (>80%) via roller compaction for hot-melt coating process optimization. The selected API was ibuprofen sodium dihydrate, a salt of ibuprofen with improved bioavailability and poor intrinsic compactibility. The formulation and roller compaction process were developed for the production of granules with 94%w/w of API and low friability (∼30%), using sorbitol and isomalt as excipients. The strong bonding mechanism relied on powder jamming prior to the rollers and was investigated via scanning electron microscopy, differential scanning calorimetry and small and wide angle X-ray scattering. It was shown that sorbitol crystals are solubilized during roller compaction and recrystallize as sorbitol hydrate, acting as strong solid bridges. The robustness of the roller compaction process and the re-compaction of fines were investigated. A statistical design of experiments was conducted to evaluate the hot-melt coating process for taste masking of ibuprofen sodium granules. Taste masking required coating ratios higher than 40%w/w of granule batch, emphasizing the need for high-drug-content and abrasion-resistant granules.
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Graz, Austria; Institute of Pharmaceutical Science, Department of Pharmaceutical Technology, University of Graz, Austria.
authors.forename: Diogo Gomes
authors.initials: DG
authors.lastname: Lopes
authors.affiliation: Hermes Arzneimittel GmbH, Großhesselohe, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Garsuch
authors.affiliation: Institute of Pharmaceutical Science, Department of Pharmaceutical Technology, University of Graz, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Becker
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Graz, Austria.
authors.forename: Amrit
authors.initials: A
authors.lastname: Paudel
authors.affiliation: IOI Oleo GmbH, Witten, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Stehr
authors.affiliation: Institute of Pharmaceutical Science, Department of Pharmaceutical Technology, University of Graz, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Graz, Austria. Electronic address: sharareh.salar-behzadi@tugraz.at.
authors.forename: Sharareh
authors.initials: S
authors.lastname: Salar-Behzadi
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D019245:Compressive Strength; D006358:Hot Temperature; D007052:Ibuprofen / Q000138:chemical synthesis*; D013012:Sorbitol / Q000138:chemical synthesis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013012:Sorbitol; D007052:Ibuprofen
keywords: Hot-melt coating; Multiparticulate system; Roller compaction; Sodium ibuprofen dihydrate; Sorbitol hydrate; Taste-masking