title: Effects of Chamber Pressure and Partial Pressure of Water Vapor on Secondary Drying in Lyophilization.
abstract: Secondary drying is the final step of lyophilization before stoppering, during which water is desorbed from the product to yield the final moisture content. We studied how chamber pressure and partial pressure of water vapor during this step affected the time course of water content of aqueous solutions of polyvinylpyrrolidone (PVP) in glass vials. The total chamber pressure had no effect when the partial pressure of water vapor was very low. However, when the vapor phase contained a substantial fraction of water vapor, the PVP moisture content was much higher. We carried out dynamic vapor sorption experiments (DVS) to demonstrate that the higher PVP moisture content was a straightforward result of the higher water vapor content in the lyophilizer. The results highlight that the partial pressure of water vapor is extremely important during secondary drying in lyophilization, and that lower chamber pressure set points for secondary drying may sometimes be justified as a strategy for ensuring low partial pressure of water vapor, especially for lyophilizers that do not inject dry gas to control pressure. These findings have direct application for process transfers/scale ups from freeze-dryers that do not inject dry gas for pressure control to those that do, and vice versa.
authors.affiliation: Pfizer Global Supply, Global Technology Services, 1776 Centennial Dr., McPherson, Kansas, USA. james.searles@pfizer.com.
authors.forename: James A
authors.initials: JA
authors.lastname: Searles
authors.affiliation: Pfizer Global Supply, Global Technology Services, 1776 Centennial Dr., McPherson, Kansas, USA.|Jogue Inc, 4142 Pacific Privado, Ontario, California, 91761, USA.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Aravapalli
authors.affiliation: Pfizer BioTherapeutics Pharmaceutical Sciences Research and Development, 700 Chesterfield Parkway West, Chesterfield, Missouri, 63017, USA.
authors.forename: Cody
authors.initials: C
authors.lastname: Hodge
mesh_terms: D005612:Freeze Drying / Q000379:methods*; D010313:Partial Pressure; D011312:Pressure; D013227:Steam
chemical_list: D013227:Steam
keywords: desorption; lyophilization; polyvinylpyrrolidone; secondary drying; sorption