title: Investigation of design space for freeze-drying: use of modeling for primary drying segment of a freeze-drying cycle.
abstract: In this work, we explore the idea of using mathematical models to build design space for the primary drying portion of freeze-drying process. We start by defining design space for freeze-drying, followed by defining critical quality attributes and critical process parameters. Then using mathematical model, we build an insilico design space. Input parameters to the model (heat transfer coefficient and mass transfer resistance) were obtained from separate experimental runs. Two lyophilization runs are conducted to verify the model predictions. This confirmation of the model predictions with experimental results added to the confidence in the insilico design space. This simple step-by-step approach allowed us to minimize the number of experimental runs (preliminary runs to calculate heat transfer coefficient and mass transfer resistance plus two additional experimental runs to verify model predictions) required to define the design space. The established design space can then be used to understand the influence of critical process parameters on the critical quality attributes for all future cycles.
authors.affiliation: Pfizer Global Research and Development, Groton, Connecticut 06340, USA. venkat.koganti@pfizer.com
authors.forename: Venkat Rao
authors.initials: VR
authors.lastname: Koganti
authors.forename: Evgenyi Y
authors.initials: EY
authors.lastname: Shalaev
authors.forename: Mark R
authors.initials: MR
authors.lastname: Berry
authors.forename: Thomas
authors.initials: T
authors.lastname: Osterberg
authors.forename: Maickel
authors.initials: M
authors.lastname: Youssef
authors.forename: David N
authors.initials: DN
authors.lastname: Hiebert
authors.forename: Frank A
authors.initials: FA
authors.lastname: Kanka
authors.forename: Martin
authors.initials: M
authors.lastname: Nolan
authors.forename: Rosemary
authors.initials: R
authors.lastname: Barrett
authors.forename: Gioval
authors.initials: G
authors.lastname: Scalzo
authors.forename: Gillian
authors.initials: G
authors.lastname: Fitzpatrick
authors.forename: Niall
authors.initials: N
authors.lastname: Fitzgibbon
authors.forename: Sumit
authors.initials: S
authors.lastname: Luthra
authors.forename: Liling
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D005612:Freeze Drying / Q000379:methods*; D008956:Models, Chemical; D011786:Quality Control; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature; D014835:Volatilization; D014867:Water
chemical_list: D014867:Water