title: Advanced stable lipid-based formulations for a patient-centric product design.
abstract: Multiparticulate dosage forms are a recent strategy to meet the special needs of children, elderly people and patients suffering from dysphagia. Our study presents a novel and cost-efficient approach for the manufacturing of a taste-masked multiparticulate system with a stable immediate release profile by applying lipid-based excipients in a solvent-free hot melt coating process. The thermosensitive N-acetylcysteine (N-ac) was used as model drug and hot-melt coated with a mixture of tripalmitin and polysorbate 65. A predictive in vitro method for the evaluation of the taste masking efficiency was developed based on the deprotonation of the carboxyl group of N-ac and the decline of pH, responsible for the unpleasant sour taste of the compound. The method was confirmed using in vivo studies. Differential scanning calorimetry and X-ray scattering experiments revealed polymorphic transformation and its dependency on transformation time, temperature and emulsifier concentration. During the process, the coating was transformed almost completely into the stable β-polymorph, leading to an unaltered dissolution profile during storage. A statistical design was conducted that revealed the critical process parameters affecting the taste masking efficiency and drug release. This study shows the successful application of solvent-free hot-melt coating in the development of a taste-masked and stable formulation.
authors.affiliation: Institute of Pharmaceutical Science, Department of Pharmaceutical Technology, University of Graz, Graz, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Becker
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Graz, Austria.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Saurugger
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Graz, Austria.
authors.forename: Diana
authors.initials: D
authors.lastname: Kienberger
authors.affiliation: Institute of Pharmaceutical Science, Department of Pharmaceutical Technology, University of Graz, Graz, Austria; Research Center Pharmaceutical Engineering GmbH, Graz, Austria.
authors.forename: Diogo
authors.initials: D
authors.lastname: Lopes
authors.affiliation: Hermes Arzneimittel GmbH, Großhesselohe, Germany.
authors.forename: Detlev
authors.initials: D
authors.lastname: Haack
authors.affiliation: Hermes Arzneimittel GmbH, Großhesselohe, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Köberle
authors.affiliation: Cremer Oleo GmbH & Co. KG, Witten, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Stehr
authors.affiliation: Cremer Oleo GmbH & Co. KG, Witten, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Lochmann
authors.affiliation: Institute of Pharmaceutical Science, Department of Pharmaceutical Technology, University of Graz, 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: D000111:Acetylcysteine / Q000737:chemistry* / Q000494:pharmacology; D000328:Adult; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003198:Computer Simulation; D065546:Drug Liberation; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry*; D012995:Solubility; D013649:Taste / Q000187:drug effects; D013678:Technology, Pharmaceutical / Q000379:methods*; D014280:Triglycerides / Q000737:chemistry*; D055815:Young Adult
chemical_list: D005079:Excipients; D011136:Polysorbates; D014280:Triglycerides; C005859:tripalmitin; D000111:Acetylcysteine
keywords: Hot-melt coating; Immediate release; Multiparticulate dosage forms; Polymorph; Stability; Taste masking; Triglyceride