title: Application of ICH Q9 Quality Risk Management Tools for Advanced Development of Hot Melt Coated Multiparticulate Systems.
abstract: This study aimed to apply quality risk management based on the The International Conference on Harmonisation guideline Q9 for the early development stage of hot melt coated multiparticulate systems for oral administration. N-acetylcysteine crystals were coated with a formulation composing tripalmitin and polysorbate 65. The critical quality attributes (CQAs) were initially prioritized using failure mode and effects analysis. The CQAs of the coated material were defined as particle size, taste-masking efficiency, and immediate release profile. The hot melt coated process was characterized via a flowchart, based on the identified potential critical process parameters (CPPs) and their impact on the CQAs. These CPPs were prioritized using a process failure mode, effects, and criticality analysis and their critical impact on the CQAs was experimentally confirmed using a statistical design of experiments. Spray rate, atomization air pressure, and air flow rate were identified as CPPs. Coating amount and content of polysorbate 65 in the coating formulation were identified as critical material attributes. A hazard and critical control points analysis was applied to define control strategies at the critical process points. A fault tree analysis evaluated causes for potential process failures. We successfully demonstrated that a standardized quality risk management approach optimizes the product development sustainability and supports the regulatory aspects.
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmaceutical Sciences, University of Graz, Universitätsplatz 1, Graz 8010, Austria.
authors.forename: Elena
authors.initials: E
authors.lastname: Stocker
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmaceutical Sciences, University of Graz, Universitätsplatz 1, Graz 8010, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Becker
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, Heine (Robert E.) Pharmacy Bldg, 575 W Stadium Ave, West Lafayette, Indiana 47907.
authors.forename: Siddhi
authors.initials: S
authors.lastname: Hate
authors.affiliation: Research Center Pharmaceutical Engineering (RCPE) GmbH, Inffeldgasse 13, Graz 8010, Austria.
authors.forename: Roland
authors.initials: R
authors.lastname: Hohl
authors.affiliation: Hermes Arzneimittel GmbH, Großhesselohe, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schiemenz
authors.affiliation: Research Center Pharmaceutical Engineering (RCPE) GmbH, Inffeldgasse 13, Graz 8010, Austria.
authors.forename: Stephan
authors.initials: S
authors.lastname: Sacher
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmaceutical Sciences, University of Graz, Universitätsplatz 1, Graz 8010, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
authors.affiliation: Research Center Pharmaceutical Engineering (RCPE) GmbH, Inffeldgasse 13, Graz 8010, Austria. Electronic address: sharareh.salar-behzadi@tugraz.at.
authors.forename: Sharareh
authors.initials: S
authors.lastname: Salar-Behzadi
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000737:chemistry*; D000284:Administration, Oral; D000998:Antiviral Agents / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000737:chemistry*; D005615:Freezing; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry*; D012995:Solubility; D013055:Spectrophotometry, Infrared; D014280:Triglycerides / Q000737:chemistry*
chemical_list: D000998:Antiviral Agents; D004337:Drug Carriers; D005079:Excipients; D016166:Free Radical Scavengers; D011136:Polysorbates; D014280:Triglycerides; C005859:tripalmitin; D000111:Acetylcysteine
keywords: coating; dissolution; factorial design; fluid bed; formulation; infrared spectroscopy; lipids; oral drug delivery; particle size