title: Evaluation of Different Holder Devices for Freeze-Drying in Dual-Chamber Cartridges With a Focus on Energy Transfer.
abstract: For freeze-drying in dual-chamber cartridges, a holder device to enable handling and safe positioning in the freeze-dryer is necessary. The aim of this study was to analyze 4 different types of holder devices and to define the best system based on energy transfer. The main criteria were drying homogeneity, ability to minimize the influence of atypical radiation on product temperatures, and heat transfer effectiveness. The shell holder reduced the influence of atypical radiation by almost 60% compared to a block system and yielded the most homogenous sublimation rates. Besides the most efficient heat transfer with values of 1.58E-4 ± 2.06E-6 cal/(s*cm2*K) at 60 mTorr to 3.63E-4 ± 1.85E-5 cal/(s*cm2*K) at 200 mTorr for Ktot, reaction times to shelf temperature changes were up to 4 times shorter compared to the other holder systems and even faster than for vials. The flexible holder provided a comparable shielding against atypical radiation as the shell but introduced a third barrier against energy transfer. Block and guardrail holder were the least efficient system tested. Hence, the shell holder provided the best radiation shielding, enhanced the transferability of the results to a larger scale, and improved the homogeneity between the dual-chamber cartridges.
authors.affiliation: Ludwig-Maximilians-Universitaet, Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Munich D-81377, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Korpus
authors.affiliation: Ludwig-Maximilians-Universitaet, Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Munich D-81377, Germany. Electronic address: wolfgang.friess@cup.uni-muenchen.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Friess
mesh_terms: D004735:Energy Transfer; D005612:Freeze Drying / Q000295:instrumentation / Q000379:methods / Q000592:standards; D008353:Mannitol / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods / Q000592:standards*
chemical_list: D008353:Mannitol
keywords: formulation; freeze-drying/lyophilization; injectables; lyophilization; mathematical model; process analytical technology (PAT); protein formulation