title: A Systematic Approach of Employing Quality by Design Principles: Risk Assessment and Design of Experiments to Demonstrate Process Understanding and Identify the Critical Process Parameters for Coating of the Ethylcellulose Pseudolatex Dispersion Using Non-Conventional Fluid Bed Process.
abstract: The goal of this study was to utilize risk assessment techniques and statistical design of experiments (DoE) to gain process understanding and to identify critical process parameters for the manufacture of controlled release multiparticulate beads using a novel disk-jet fluid bed technology. The material attributes and process parameters were systematically assessed using the Ishikawa fish bone diagram and failure mode and effect analysis (FMEA) risk assessment methods. The high risk attributes identified by the FMEA analysis were further explored using resolution V fractional factorial design. To gain an understanding of the processing parameters, a resolution V fractional factorial study was conducted. Using knowledge gained from the resolution V study, a resolution IV fractional factorial study was conducted; the purpose of this IV study was to identify the critical process parameters (CPP) that impact the critical quality attributes and understand the influence of these parameters on film formation. For both studies, the microclimate, atomization pressure, inlet air volume, product temperature (during spraying and curing), curing time, and percent solids in the coating solutions were studied. The responses evaluated were percent agglomeration, percent fines, percent yield, bead aspect ratio, median particle size diameter (d50), assay, and drug release rate. Pyrobuttons® were used to record real-time temperature and humidity changes in the fluid bed. The risk assessment methods and process analytical tools helped to understand the novel disk-jet technology and to systematically develop models of the coating process parameters like process efficiency and the extent of curing during the coating process.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, 20N Pine Street, Baltimore, Maryland, 21201, USA.|Amneal Pharmaceuticals, Brookhaven, NY, 11719, USA.
authors.forename: Bhaveshkumar H
authors.initials: BH
authors.lastname: Kothari
authors.affiliation: Office of New Animal Drug Evaluation, Center for Veterinary Medicine, US Food and Drug Administration, Rockville, Maryland, 20855, USA.
authors.forename: Raafat
authors.initials: R
authors.lastname: Fahmy
authors.affiliation: Office of New Animal Drug Evaluation, Center for Veterinary Medicine, US Food and Drug Administration, Rockville, Maryland, 20855, USA.
authors.forename: H Gregg
authors.initials: HG
authors.lastname: Claycamp
authors.affiliation: Office of Process and Facilities, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, 20993, USA.|Merck Research Laboratories, West Point, PA, 19486, USA.
authors.forename: Christine M V
authors.initials: CMV
authors.lastname: Moore
authors.affiliation: Office of Process and Facilities, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, 20993, USA.
authors.forename: Sharmista
authors.initials: S
authors.lastname: Chatterjee
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, 20N Pine Street, Baltimore, Maryland, 21201, USA. shoag@rx.umaryland.edu.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Hoag
mesh_terms: D002482:Cellulose / Q000031:analogs & derivatives* / Q000494:pharmacology; D003627:Data Interpretation, Statistical; D003692:Delayed-Action Preparations / Q000494:pharmacology*; D065546:Drug Liberation; D005079:Excipients / Q000494:pharmacology; D010316:Particle Size; D012107:Research Design; D018570:Risk Assessment / Q000379:methods*; D013608:Tablets, Enteric-Coated
chemical_list: D003692:Delayed-Action Preparations; D005079:Excipients; D013608:Tablets, Enteric-Coated; C013517:ethyl cellulose; D002482:Cellulose
keywords: design of experiments and Pyrobutton®; ethylcellulose; fluid bed technology; quality by design; risk assessment