Abstract
Controlling the ice nucleation temperature during the freeze phase of lyophilization is an area that has grown significantly in importance in the recent past. Different Controlled Ice Nucleation (CIN) techniques investigated in the pharmaceutical industry are discussed in this chapter, along with their limitations for commercial implementation. Recent work using the ControLyo® pressurization and depressurization technology is further discussed, along with a discussion of CIN cycle design. This book chapter also explores how ControLyo® CIN technology could be used to enable a Quality by Design (QbD) approach for the freeze phase of lyophilization cycles.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Schneid SC, Gieseler H (2012) Rational approaches and transfer strategies for the scale-up of freeze-drying cycles. Chemistry Today 30(2):9–12
Tang X, Pikal MJ (2004) Design of freeze-drying process for pharmaceuticals: practical advice. Pharm Res 21(2):191–200
Konstantinidis AK, Kuu W, Otten L, Nail SL, Sever RR (2011) Controlled nucleation in freeze-drying: effects on pore size in the dried product later, mass transfer resistance, and primary drying rate. J Pharm Sci 100(8):3458–3470
Searles JA, Carpenter T, Randolph TW (2001) The ice nucleation temperature determines the primary drying rate of lyophilization for samples frozen on a temperature controlled shelf. J Pharm Sci 90(7):860–871
Bursac R, Sever R, Hunek B (2009) A practical method for resolving the nucleation problem in lyophilization. BioProcess Int 7(9):66–72
Williams NA, Lee Y, Polli GP, Jennings TA (1986) The effects of cooling rate on solid phase transitions and associated vial breakage occurring in frozen mannitol solution. J Parenter Sci Technol 40(4):135–141
Allmendinger A et al (2016) Controlled nucleation during freeze drying using vacuum-induced surface freezing. Database no. 633018. http://www.researchdisclosure.com
Rambhatla S, Ramot R, Bhugra C, Pikal MJ (2004) Heat and mass transfer scale-up issues during freeze drying: II. Control and characterization of the degree of supercooling. AAPS PharmSciTech 5(4):54–62
Winter G (2015) Current trends and challenge in freeze drying of biologics. ISLFD 7th International Conference, Barcelona
Morris GJ, Acton E (2013) Controlled ice nucleation in cryopreservation – a review. Cryobiology 66(2):85–92
Petersen A, Schneider H, Rau G, Glasmacher B (2006) New approach for freezing aqueous solutions under active control of the nucleation temperature. Cryobiology 53(2):248–257
Hobbs PV (1974) Ice physics. Oxford University Press, New York, NY
Tsotsas E, Mujumdar AS (2011) Modern drying technology, volume 3: product quality and formulation. Wiley-VCH, Weinheim
Mudhivarthi VK (2015) Controlled ice nucleation in freeze drying: freezing heterogeneity and protein stability. SP Scientific Lyolearn Webinar. http://www.spscientific.com/LyoTech-Center/LyoLearn-Webinars-Archive.aspx
Wang B (2016) Application of controlled nucleation during lyophilization to improve cake appearance and product quality. SP Scientific Lyolearn Webinar. http://www.spscientific.com/LyoTech-Center/LyoLearn-Webinars-Archive.aspx
Awotwe-Otoo D, Agarabi C, Read EK, Lute S, Brorson KA, Khan MA, Shah RB (2013) Impact of controlled ice nucleation on process performance and quality attributes of a lyophilized monoclonal antibody. Int J Pharm 450(1-2):70–78
Magill G (2015) Application of controlled ice nucleation for lyophilization of a low glass transition temperature solution. PepTalk Conference Podium Presentation–Cambridge Healthtech Institute’s 14th Annual Conference
Patapoff T, Overcashier D (2002) The importance of freezing on lyophilization cycle development. BioPharm 15(3):16–21 72
Pongsawatmanit R, Miyawaki O (1993) Measurement of temperature-dependent ice fraction in frozen foods. Biosci Biotechnol Biochem 57(10):1650–1654
Bhatnagar BS, Bogner RH, Pikal MJ (2007) Protein stability during freezing: separation of stresses and mechanisms of protein stabilization. Pharm Dev Technol 12(5):505–523
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Luoma, J., Magill, G., Kumar, L., Yusoff, Z. (2019). Controlled Ice Nucleation Using ControLyo® Pressurization-Depressurization Method. In: Ward, K., Matejtschuk, P. (eds) Lyophilization of Pharmaceuticals and Biologicals. Methods in Pharmacology and Toxicology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8928-7_3
Download citation
DOI: https://doi.org/10.1007/978-1-4939-8928-7_3
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-8927-0
Online ISBN: 978-1-4939-8928-7
eBook Packages: Springer Protocols