title: Accurate prediction of collapse temperature using optical coherence tomography-based freeze-drying microscopy.
abstract: The objective of this study was to assess the feasibility of developing and applying a laboratory tool that can provide three-dimensional product structural information during freeze-drying and which can accurately characterize the collapse temperature (Tc ) of pharmaceutical formulations designed for freeze-drying. A single-vial freeze dryer coupled with optical coherence tomography freeze-drying microscopy (OCT-FDM) was developed to investigate the structure and Tc of formulations in pharmaceutically relevant products containers (i.e., freeze-drying in vials). OCT-FDM was used to measure the Tc and eutectic melt of three formulations in freeze-drying vials. The Tc as measured by OCT-FDM was found to be predictive of freeze-drying with a batch of vials in a conventional laboratory freeze dryer. The freeze-drying cycles developed using OCT-FDM data, as compared with traditional light transmission freeze-drying microscopy (LT-FDM), resulted in a significant reduction in primary drying time, which could result in a substantial reduction of manufacturing costs while maintaining product quality. OCT-FDM provides quantitative data to justify freeze-drying at temperatures higher than the Tc measured by LT-FDM and provides a reliable upper limit to setting a product temperature in primary drying.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut 06269.
authors.forename: Kristyn
authors.initials: K
authors.lastname: Greco
authors.affiliation: Physical Sciences, Inc., Andover, Massachusetts 01810.
authors.forename: Mircea
authors.initials: M
authors.lastname: Mujat
authors.affiliation: Physical Sciences, Inc., Andover, Massachusetts 01810.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Galbally-Kinney
authors.affiliation: Physical Sciences, Inc., Andover, Massachusetts 01810.
authors.forename: Daniel X
authors.initials: DX
authors.lastname: Hammer
authors.affiliation: Physical Sciences, Inc., Andover, Massachusetts 01810.
authors.forename: R Daniel
authors.initials: RD
authors.lastname: Ferguson
authors.affiliation: Physical Sciences, Inc., Andover, Massachusetts 01810.
authors.forename: Nicusor
authors.initials: N
authors.lastname: Iftimia
authors.affiliation: Physical Sciences, Inc., Andover, Massachusetts 01810.
authors.forename: Phillip
authors.initials: P
authors.lastname: Mulhall
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut 06269.
authors.forename: Puneet
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Physical Sciences, Inc., Andover, Massachusetts 01810.
authors.forename: William J
authors.initials: WJ
authors.lastname: Kessler
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut 06269. Electronic address: michael.pikal@uconn.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pikal
mesh_terms: D000818:Animals; D002417:Cattle; D004867:Equipment Design; D005612:Freeze Drying / Q000295:instrumentation / Q000379:methods*; D008853:Microscopy / Q000295:instrumentation / Q000379:methods*; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013395:Sucrose / Q000737:chemistry; D041623:Tomography, Optical Coherence / Q000295:instrumentation / Q000379:methods*; D044366:Transition Temperature
chemical_list: D012710:Serum Albumin, Bovine; D013395:Sucrose