title: Particle engineering: a strategy for establishing drug substance physical property specifications during small molecule development.
abstract: A strategy for physical property control of a drug substance has been developed that utilizes a science-based approach to define key drivers for particle control. These drivers are based on in vivo performance (or expected performance), content uniformity of the drug substance in drug product, and manufacturability of drug product. Quality by design principles have been used in developing the strategy. The strategy has been designed to provide expectations in terms of particle control at each state of development, translating to early-phase projects and carrying through until launch and beyond.
authors.affiliation: Product Research and Development Eli Lilly and Company, Indianapolis, Indiana 46285, USA. rgiacocca@lilly.com
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Iacocca
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Burcham
authors.forename: Lori R
authors.initials: LR
authors.lastname: Hilden
mesh_terms: D000284:Administration, Oral; D055598:Chemical Phenomena; D003663:Decision Trees; D015195:Drug Design; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D008956:Models, Chemical; D010316:Particle Size; D010599:Pharmacokinetics; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry*; D012984:Software; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*
chemical_list: D054852:Small Molecule Libraries