Application of ICH Q9 Quality Risk Management Tools for Advanced Development of Hot Melt Coated Multiparticulate Systems

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• 作者：Elena Stocker¹ ; Karin Becker¹ ; Siddhi Hate² ; Roland Hohl³ ; Wolfgang Schiemenz⁴ ; Stephan Sacher³ ; Andreas Zimmer¹ ; Sharareh Salar-Behzadi³ ; ^{sharareh.salar-behzadi@tugraz.at}
• 关键词：lipids ; infrared spectroscopy ; formulation ; fluid bed ; factorial design ; coating ; dissolution ; oral drug delivery ; particle size
• 刊名：Journal of Pharmaceutical Sciences
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：106
• 期：1
• 页码：278-290
• 全文大小：2207 K
• 卷排序：106

文摘

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.