title: Application of quality by design (QbD) approach to ultrasonic atomization spray coating of drug-eluting stents.
abstract: The drug coating process for coated drug-eluting stents (DES) has been identified as a key source of inter- and intra-batch variability in drug elution rates. Quality-by-design (QbD) principles were applied to gain an understanding of the ultrasonic spray coating process of DES. Statistically based design of experiments (DOE) were used to understand the relationship between ultrasonic atomization spray coating parameters and dependent variables such as coating mass ratio, roughness, drug solid state composite microstructure, and elution kinetics. Defect-free DES coatings composed of 70% 85:15 poly(DL-lactide-co-glycolide) and 30% everolimus were fabricated with a constant coating mass. The drug elution profile was characterized by a mathematical model describing biphasic release kinetics. Model coefficients were analyzed as a DOE response. Changes in ultrasonic coating processing conditions resulted in substantial changes in roughness and elution kinetics. Based on the outcome from the DOE study, a design space was defined in terms of the critical coating process parameters resulting in optimum coating roughness and drug elution. This QbD methodology can be useful to enhance the quality of coated DES.
authors.affiliation: Division of Biology, Chemistry and Materials Science, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993, USA, Martin.McDermott@fda.hhs.gov.
authors.forename: Martin
authors.initials: M
authors.lastname: McDermott
authors.forename: Sharmista
authors.initials: S
authors.lastname: Chatterjee
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Hu
authors.forename: Ariel
authors.initials: A
authors.lastname: Ash-Shakoor
authors.forename: Reginald
authors.initials: R
authors.lastname: Avery
authors.forename: Anastasiya
authors.initials: A
authors.lastname: Belyaeva
authors.forename: Celia
authors.initials: C
authors.lastname: Cruz
authors.forename: Minerva
authors.initials: M
authors.lastname: Hughes
authors.forename: Joanne
authors.initials: J
authors.lastname: Leadbetter
authors.forename: Conrad
authors.initials: C
authors.lastname: Merkle
authors.forename: Taylor
authors.initials: T
authors.lastname: Moot
authors.forename: Sepideh
authors.initials: S
authors.lastname: Parvinian
authors.forename: Dinesh
authors.initials: D
authors.lastname: Patwardhan
authors.forename: David
authors.initials: D
authors.lastname: Saylor
authors.forename: Nancy
authors.initials: N
authors.lastname: Tang
authors.forename: Tina
authors.initials: T
authors.lastname: Zhang
mesh_terms: D002851:Chromatography, High Pressure Liquid; D054855:Drug-Eluting Stents; D000068338:Everolimus / Q000737:chemistry / Q000493:pharmacokinetics; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D011098:Polyglactin 910; D013499:Surface Properties; D014465:Ultrasonics
chemical_list: D011098:Polyglactin 910; D000068338:Everolimus