Development of a Single Vial Mass Flow Rate Monitor to Assess Pharmaceutical Freeze Drying Heterogeneity.
CFD
Freeze-drying
Heterogeneous freeze-drying
Lyophilization
TDLAS
Journal
AAPS PharmSciTech
ISSN: 1530-9932
Titre abrégé: AAPS PharmSciTech
Pays: United States
ID NLM: 100960111
Informations de publication
Date de publication:
17 Oct 2024
17 Oct 2024
Historique:
received:
12
06
2024
accepted:
25
09
2024
medline:
18
10
2024
pubmed:
18
10
2024
entrez:
17
10
2024
Statut:
epublish
Résumé
During pharmaceutical lyophilization processes, inter-vial drying heterogeneity remains a significant obstacle. Due to differences in heat and mass transfer based on vial position within the freeze drier, edge vials freeze differently, are typically warmer and dry faster than center vials. This vial position-dependent heterogeneity within the freeze dryer leads to tradeoffs during process development. During primary drying, process developers must be careful to avoid shelf temperatures that would result in overheating of edge vials causing the product sublimation interface temperature to rise above the critical (collapse) temperature. However, at lower shelf temperatures, center vials require longer to complete primary drying, risking collapse or melt-back due to incomplete drying. Both situations may result in poor product quality affecting drug stability, activity, and reconstitution times. We present a new approach for monitoring vial location-specific water vapor mass flow based on Tunable Diode Laser Absorption Spectroscopy (TDLAS). The single vial monitor enables measurement of the gas flow velocity, water vapor temperature, and gas concentration from the sublimating ice, enabling the calculation of the mass flow rate which can be used in combination with a heat and mass transfer model to determine vial heat transfer coefficients and product resistance to drying. These parameters can in turn be used for robust and rapid process development and control.
Identifiants
pubmed: 39419936
doi: 10.1208/s12249-024-02961-0
pii: 10.1208/s12249-024-02961-0
doi:
Substances chimiques
Water
059QF0KO0R
Pharmaceutical Preparations
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
245Informations de copyright
© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.
Références
Tang X, Pikal MJ. Design of freeze-drying processes for pharmaceuticals: practical advice. Pharm Res. 2004;21:191–200.
doi: 10.1023/B:PHAM.0000016234.73023.75
pubmed: 15032301
Fissore D, Pisano R, Barresi AA. Process analytical technology for monitoring pharmaceuticals freeze-drying–A comprehensive review. Dry Technol [Internet]. 2018;36:1839–65. Available from: https://doi.org/10.1080/07373937.2018.1440590 .
Bourlès E, de Lannoy G, Scutella B, Fonseca F, Trelea IC, Passot S. Scale-up of freeze drying cycles, the use of Process Analytical Technology (PAT) and statistical analysis. Lyophilization Pharm Biol New Technol Approaches. 2019; 2:215–40.
Kawasaki H, Shimanouchi T, Kimura Y. Recent development of optimization of lyophilization process. J Chem. 2019;2019:1–14.
Tsinontides SC, Rajniak P, Pham D, Hunke WA, Placek J, Reynolds SD. Freeze drying - Principles and practice for successful scale-up to manufacturing. Int J Pharm. 2004;280:1–16.
doi: 10.1016/j.ijpharm.2004.04.018
pubmed: 15265542
Chang BS, Reilly M, Chang H. Lyophilized Biologics. In: Varshney D, Singh M, editors. Lyophilized Biol Vaccines Modality-Based Approaches [Internet]. New York, NY: Springer New York; 2015. p. 93–119. Available from: https://doi.org/10.1007/978-1-4939-2383-0_6
Bogner R, Gong E, Kessler W, Hinds M, Manchanda A, Yoon S, et al. A software tool for lyophilization primary drying process development and scale-up including process heterogeneity, i: laboratory-scale model testing. AAPS PharmSciTech. 2021;22:1–16.
doi: 10.1208/s12249-021-02134-3
Sharma P, Kessler WJ, Bogner R, Thakur M, Pikal MJ. Applications of the tunable diode laser absorption spectroscopy: in-process estimation of primary drying heterogeneity and product temperature during lyophilization. J Pharm Sci [Internet]. 2018;108:416–30. Available from: https://doi.org/10.1016/j.xphs.2018.07.031 .
Scutellà B, Plana-Fattori A, Passot S, Bourlès E, Fonseca F, Flick D, et al. 3D mathematical modelling to understand atypical heat transfer observed in vial freeze-drying. Appl Therm Eng. 2017;126:226–36.
doi: 10.1016/j.applthermaleng.2017.07.096
Juckers A, Knerr P, Harms F, Strube J. Advanced process analytical technology in combination with process modeling for endpoint and model parameter determination in lyophilization process design and optimization. Processes. 2021;9(9):1600.
Colucci D, Fissore D, Barresi AA, Braatz RD. A new mathematical model for monitoring the temporal evolution of the ice crystal size distribution during freezing in pharmaceutical solutions. Eur J Pharm Biopharm. 2020;148:148–59.
doi: 10.1016/j.ejpb.2020.01.004
pubmed: 31953190
Kuu WY, Nail SL, Hardwick LM. Determination of shelf heat transfer coefficients along the shelf flow path of a freeze dryer using the shelf fluid temperature perturbation approach. Pharm Dev Technol. 2007;12:485–94.
doi: 10.1080/10837450701481223
pubmed: 17963149
Kessler WJ, Sharma P, Mujat M. Advances in instrumental analysis applied to the development of lyophilization cycles. In: Varshney D, Singh M, editors. Lyophilized biologics and vaccines modality-based approaches. New York: Springer New York; 2015. pp. 43–72. https://doi.org/10.1007/978-1-4939-2383-0_4 .
Chia A, Bouchard J, Poulin É, Lapointe-Garant PP. Model development for the design of control strategies of the primary drying of lyophilization in vials. Dry Technol [Internet]. 2021;0:1–18. Available from: https://doi.org/10.1080/07373937.2021.2023563 .
Patel SM, Pikal MJ. Lyophilization process design space. J Pharm Sci. 2013;102:3883–7.
doi: 10.1002/jps.23703
pubmed: 23946165
von Graberg S. Freeze drying from small containers: heat and mass transfer and implications on process design. Friedrich-Alexander_Universitat Erlangen-Nurmberg. 2011. https://open.fau.de/handle/openfau/1882 .
Pansare SK, Patel SM. Lyophilization process design and development: a single-step drying approach. J Pharm Sci [Internet]. 2019;108:1423–33. Available from: https://doi.org/10.1016/j.xphs.2018.11.021 .
Vanbillemont PB. Development and evaluation of next-generation pharmaceutical freeze-drying technologies. Ghent University. 2020. biblio.ugent.be/publication/8676512 .
Pikal MJ, Pande P, Bogner R, Sane P, Mudhivarthi V, Sharma P. Impact of natural variations in freeze-drying parameters on product temperature history: application of quasi steady-state heat and mass transfer and simple statistics. AAPS PharmSciTech. 2018;19:2828–42.
doi: 10.1208/s12249-018-1155-4
pubmed: 30259404
Kessler WJ, Gong E. Tunable diode laser absorption spectroscopy in lyophilization. In: Ward KR, Matejtschuk P, editors. Lyophilization pharm biol new technol approaches [Internet]. New York, NY: Springer New York; 2019. p. 113–41. Available from: https://doi.org/10.1007/978-1-4939-8928-7_5 .
Wenzel T, Gieseler H. Molded vial manufacturing and its impact on heat transfer during freeze-drying: vial geometry considerations. AAPS PharmSciTech. 2021;22:57.
Roy ML, Pikal MJ. Process control in freeze drying: determination of the end point of sublimation drying by an electronic moisture sensor. J Parenter Sci Technol a Publ Parenter Drug Assoc. 1989;43:60–6.
Kawasaki H, Shimanouchi T, Sawada H, Hosomi H, Hamabe Y, Kimura Y. Temperature measurement by sublimation rate as a process analytical technology tool in lyophilization. J Pharm Sci [Internet]. 2019;108:2305–14. Available from: https://doi.org/10.1016/j.xphs.2019.02.015
Demichela M, Barresi AA, Baldissone G. The effect of human error on the temperature monitoring and control of freeze drying processes by means of thermocouples. Front Chem. 2018;6:1–11.
doi: 10.3389/fchem.2018.00419
Barresi A, Ghio S, Fissore D, Pisano R. Freeze drying of pharmaceutical excipients close to collapse temperature: influence of the process conditions on process time and product quality. Dry Technol. 2009;27:805–16.
doi: 10.1080/07373930902901646
Gieseler H, Kessler WJ, Finson M, Davis SJ, Mulhall PA, Bons V, et al. Evaluation of tunable diode laser absorption spectroscopy for in-process water vapor mass flux measurements during freeze drying. J Pharm Sci. 2007;96:1776–93.
doi: 10.1002/jps.20827
pubmed: 17221854
Pikal MJ. Use of laboratory data in freeze drying process design: heat and mass transfer coefficients and the computer simulation of freeze drying. J Parenter Sci Technol a Publ Parenter Drug Assoc. 1985;39:115–39.
Kazarin P, Kessler W, Gong E, Yoon S, Liu H, Marx R, et al. A compact model for lyophilizer equipment capability estimation. AAPS PharmSciTech [Internet]. 2021;23:14. Available from: https://doi.org/10.1208/s12249-021-02167-8 .
Pisano R, Fissore D, Velardi SA, Barresi AA. In-line optimization and control of an industrial freeze-drying process for pharmaceuticals. J Pharm Sci [Internet]. 2010;99:4691–709. Available from: https://doi.org/10.1002/jps.22166 .
Pikal MJ, Cardon S, Bhugra C, Jameel F, Rambhatla S, Mascarenhas WJ, et al. The nonsteady state modeling of freeze drying: in-process product temperature and moisture content mapping and pharmaceutical product quality applications. Pharm Dev Technol. 2005;10:17–32.
doi: 10.1081/PDT-35869
pubmed: 15776810
Liapis AI, Bruttini R. Freeze-drying of pharmaceutical crystalline and amorphous solutes in vials: dynamic multi-dimensional models of the primary and secondary drying stages and qualitative features of the moving interface. Dry Technol [Internet]. 1995;13:43–72. Available from: https://doi.org/10.1080/07373939508916942 .
Kamenik B, Hriberšek M, Zadravec M. Determination of pressure resistance of a partially stoppered vial by using a coupled CFD-0D model of lyophilization. Eur J Pharm Biopharm. 2022;175:53–64.
doi: 10.1016/j.ejpb.2022.04.010
pubmed: 35562001
Pikal MJ, Roy ML, Shah S. Mass and heat transfer in vial freeze-drying of pharmaceuticals: role of the vial. J Pharm Innov. 1984;73:1224–37.
Nail SL, Searles JA. Elements of quality by design in development and scale-up of freeze-dried parenterals. BioPharm Int. 2008;21:44–52.
Jameel F, Alexeenko A, Bhambhani A, Sacha G, Zhu T, Tchessalov S, et al. Recommended best practices for lyophilization validation—2021 Part I: process design and modeling. AAPS PharmSciTech. 2021;22:221.
Patel SM, Doen T, Pikal MJ. Determination of end point of primary drying in freeze-drying process control. AAPS PharmSciTech. 2010;11:73–84.
doi: 10.1208/s12249-009-9362-7
pubmed: 20058107
pmcid: 2850457
Omega. Table of total emissivity. pp. 88–9. https://assets.omega.com/tech-ref-legacy-pdfs/z088-089.pdf .
Patel SM, Chaudhuri S, Pikal MJ. Choked flow and importance of Mach I in freeze-drying process design. Chem Eng Sci [Internet]. 2010;65:5716–27. Available from: https://doi.org/10.1016/j.ces.2010.07.024 .
Launder BE (Brian E. Lectures in mathematical models of turbulence [by] B. E. Launder and D. B. Spalding. Spalding 1923- DB (Dudley B, editor. London, New York: Academic Press; 1972.
Scutellà B, Passot S, Bourlés E, Fonseca F, Tréléa IC. How Vial Geometry Variability Influences Heat Transfer and Product Temperature During Freeze-Drying. J Pharm Sci. 2017;106:770–8.
doi: 10.1016/j.xphs.2016.11.007
pubmed: 27939928
Baheti A, Kumar L, Bansal AK. Excipients used in lyophilization of small molecules. J Excipients Food Chem. 2010;1:41–54.
Rambhatla S, Tchessalov S, Pikal MJ. Heat and mass transfer scale-up issues during freeze-drying, III: Control and characterization of dryer differences via operational qualification tests. AAPS PharmSciTech. 2006;7.
Schneid SC, Gieseler H, Kessler WJ, Pikal MJ. Non-Invasive Product Temperature Determination during Primary Drying using Tunable Diode Laser Absorption Spectroscopy. J Pharm Sci. 2008;98:3406–18.
doi: 10.1002/jps.21522
Scutellà B, Trelea IC, Bourlès E, Fonseca F, Passot S. Determination of the dried product resistance variability and its influence on the product temperature in pharmaceutical freeze-drying. Eur J Pharm Biopharm [Internet]. 2018;128:379–88. Available from: https://doi.org/10.1016/j.ejpb.2018.05.004
Rambhatla S, Pikal MJ. Heat and mass transfer scale-up issues during freeze-drying, I: Atypical radiation and the edge vial effect. AAPS PharmSciTech. 2003;4:1–10.
doi: 10.1208/pt040214
Allmendinger A, Butt YL, Mietzner R, Schmidt F, Luemkemann J, Martinez CL. Controlling ice nucleation during lyophilization: Process optimization of vacuum-induced surface freezing. Processes. 2020;8:1–11.
doi: 10.3390/pr8101263
Pikal MJ, Bogner R, Mudhivarthi V, Sharma P, Sane P. Freeze-drying process development and scale-up: scale-up of edge vial versus center vial heat transfer coefficients, Kv. J Pharm Sci [Internet]. 2016;105:3333–43. Available from: https://doi.org/10.1016/j.xphs.2016.07.027
Tchessalov S, Shalaev E, Bhatnagar B, Nail S, Alexeenko A, Jameel F, et al. Best Practices and Guidelines (2022) for Scale-Up and Tech Transfer in Freeze-Drying Based on Case Studies. Part 1: Challenges during Scale Up and Transfer. AAPS PharmSciTech. 2022;24:11.
Assegehegn G, Brito-de la Fuente E, Franco JM, Gallegos C. An Experimental-Based Approach to Construct the Process Design Space of a Freeze-Drying Process: An Effective Tool to Design an Optimum and Robust Freeze-Drying Process for Pharmaceuticals. J Pharm Sci. 2020;109:785–96.