title: A Review of PAT Strategies in Secondary Solid Oral Dosage Manufacturing of Small Molecules.
abstract: Pharmaceutical solid oral dosage product manufacturing is a well-established, yet revolutionizing area. To this end, process analytical technology (PAT) involves interdisciplinary and multivariate (chemical, physical, microbiological, and mathematical) methods for material (e.g., materials, intermediates, products) and process (e.g., temperature, pressure, throughput, etc.) analysis. This supports rational process modeling and enhanced control strategies for improved product quality and process efficiency. Therefore, it is often difficult to orient and find the relevant, integrated aspects of the current state-of-the-art. Especially, the link between fundamental research, in terms of sensor and control system development, to the application both in laboratory and manufacturing scale, is difficult to comprehend. This review compiles a nonexhaustive overview on current approaches from the recognized academia and industrial practices of PAT, including screening, selection, and final implementations in solid oral dosage manufacturing, through a wide diversity of use cases. Finally, the authors attempt to extract a common consensus toward developing PAT application guidance for different unit operations of drug product manufacturing.
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria. Electronic address: stephan.laske@icloud.com.
authors.forename: Stephan
authors.initials: S
authors.lastname: Laske
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria.
authors.forename: Amrit
authors.initials: A
authors.lastname: Paudel
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria.
authors.forename: Otto
authors.initials: O
authors.lastname: Scheibelhofer
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria.
mesh_terms: D000284:Administration, Oral; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000592:standards*; D011786:Quality Control; D019265:Spectroscopy, Near-Infrared / Q000379:methods / Q000592:standards; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000592:standards*
chemical_list: D004364:Pharmaceutical Preparations
keywords: Raman spectroscopy; near-infrared spectroscopy; process analytical technology; processing; solid dosage form