title: Development of Process Analytical Technology (PAT) methods for controlled release pellet coating.
abstract: This work focused on the control of the manufacturing process for a controlled release (CR) pellet product, within a Quality by Design (QbD) framework. The manufacturing process was Wurster coating: firstly layering active pharmaceutical ingredient (API) onto sugar pellet cores and secondly a controlled release (CR) coating. For each of these two steps, development of a Process Analytical Technology (PAT) method is discussed and also a novel application of automated microscopy as the reference method. Ultimately, PAT methods should link to product performance and the two key Critical Quality Attributes (CQAs) for this CR product are assay and release rate, linked to the API and CR coating steps respectively. In this work, the link between near infra-red (NIR) spectra and those attributes was explored by chemometrics over the course of the coating process in a pilot scale industrial environment. Correlations were built between the NIR spectra and coating weight (for API amount), CR coating thickness and dissolution performance. These correlations allow the coating process to be monitored at-line and so better control of the product performance in line with QbD requirements.
authors: MSD Werthenstein Biopharma, Industrie Nord, 1, Schachen (LU), Switzerland. Electronic address: paolo_avalle@merck.com.
authors: P
authors: P
authors: Avalle
authors: MSD, Hoddesdon, United Kingdom. Electronic address: michael_pollitt@merck.com.
authors: M J
authors: MJ
authors: Pollitt
authors: MSD, Hoddesdon, United Kingdom. Electronic address: kathryn_bradley@merck.com.
authors: K
authors: K
authors: Bradley
authors: MSD, Hoddesdon, United Kingdom. Electronic address: brett_cooper@merck.com.
authors: B
authors: B
authors: Cooper
authors: MSD, Hoddesdon, United Kingdom. Electronic address: gareth_pearce@merck.com.
authors: G
authors: G
authors: Pearce
authors: MSD, Hoddesdon, United Kingdom. Electronic address: abdenour_djemai@merck.com.
authors: A
authors: A
authors: Djemai
authors: MSD, Hoddesdon, United Kingdom. Electronic address: shaun_fitzpatrick@merck.com.
authors: S
authors: S
authors: Fitzpatrick
mesh_terms: D057205:Automation, Laboratory; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002951:Citrates / Q000737:chemistry; D003692:Delayed-Action Preparations; D065347:Hypromellose Derivatives / Q000737:chemistry; D007700:Kinetics; D008747:Methylcellulose / Q000737:chemistry; D008853:Microscopy / Q000592:standards; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000592:standards; D011786:Quality Control; D012995:Solubility; D019265:Spectroscopy, Near-Infrared / Q000592:standards; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000592:standards
chemical_list: D002951:Citrates; D003692:Delayed-Action Preparations; D004364:Pharmaceutical Preparations; D065347:Hypromellose Derivatives; C013517:ethyl cellulose; C023001:ethyl citrate; D002482:Cellulose; D008747:Methylcellulose
keywords: Automated microscopy; Coated multiparticulate; Dissolution performance; Near-infrared; Pellet; Quality by Design