Spray Freezing
Boston, May 17th, 2016
2016 AAPS National Biotechnology Conference
Session: Next-Generation Drying Technologies for Processing of Biotherapeutics (#118)
Innovative Bulk Drying of Frozen Microspheres by Spray-Freeze-Drying
Bernhard LUY MERIDION Technologies, Germany
Topics • Background of the Development • Presentation of two Core Technologies – Spray Freezing – Dynamic Bulk Freeze Drying
• Case Study of an Industrial Project for a pharmaceutical product • Potential Impact of Technology on – process – product innovation – production logistics 2
© MERIDION Technologies GmbH
BioTherapeutics Pharmaceutical Sciences
Slide with kind permission from S. Tchessalov, “New life of spray freeze-drying- application to dehydration of protein solutions” PepTalk Conference 2016, San Diego CA
Recent literature on spray-freeze drying • • •
• •
•
•
Werly, E.P., Baumann, E.K., 1964. Production of submicronized powder by spray freezing.Arch. Environ. Health 9, 567–571. S.Wanning , R.Süverkrüp, A.Lamprecht. Pharmaceutical spray freeze drying, Intern. J. of Phramaceutics, 488 (2015) 136–153 Carpenter JF, Pham BV, Randolph T, Seid R, Truong-Le V. 2003. Spray freeze dry of compositions for pulmonary administration. WO2003087339. Leuenberger H, Plitzko M, Puchkov M. 2006. Spray freeze drying in a fluidized bed at normal and low pressure. Drying Technol 24(6):711–719. Cheow WS, Ng ML, Kho K, Hadinoto K. 2011. Spray-freeze-drying production of thermally sensitive polymeric nanoparticle aggregates for inhaled drug delivery: Effect of freeze-drying adjuvants. Int J Pharm 404(1–2):289–300. Gao Y, Zhu CL, Zhang XX, Gan L, Gan Y. 2011. Lipid-polymer composite microspheres for colon-specific drug delivery prepared using an ultrasonic spray freeze-drying technique. J Microencapsul 28(6):549–556. Dolly P, Anishaparvin A, Joseph GS, Anandharamakrishnan C. 2011. Microencapsulation of Lactobacillus plantarum (mtcc 5422) by spray-freezedrying method and evaluation of survival in simulated gastrointestinal conditions. J Microencapsul 28(6):568–574
Background
Typical Limitations of conventional FD • static drying (under vacuum) offers only limited heat & mass transfer • heat transfer has to occur across frozen product • vapor flow limitations, e.g. – diffusion barrier thickness
• product inhomogeneities may occur (e.g. caking, density variations)
• product handling properties (e.g. flowability, dust)
• primary packaging requirements • production logistics 4
4 © MERIDION Technologies GmbH
Background / History:
Specific past R&D work performed Research Project at Basel School of Pharmacy (Prof. Hans Leuenberger): Atmospheric Spray Freeze Drying in Fluidized Bed Operations
• started in the mid ‘80s (in coop. with Glatt GmbH) • 3 research projects realized until the mid ‘90s
5
5 © MERIDION Technologies GmbH
Background / History:
Specific past R&D work performed Atmospheric Spray Freeze Drying in Fluidized Bed
Result of Research Work: • 3 step process required (spray freezing (air temp. < -60°C); primary drying (Tp:
2016 AAPS National Biotechnology Conference
Session: Next-Generation Drying Technologies for Processing of Biotherapeutics (#118)
Innovative Bulk Drying of Frozen Microspheres by Spray-Freeze-Drying
Bernhard LUY MERIDION Technologies, Germany
Topics • Background of the Development • Presentation of two Core Technologies – Spray Freezing – Dynamic Bulk Freeze Drying
• Case Study of an Industrial Project for a pharmaceutical product • Potential Impact of Technology on – process – product innovation – production logistics 2
© MERIDION Technologies GmbH
BioTherapeutics Pharmaceutical Sciences
Slide with kind permission from S. Tchessalov, “New life of spray freeze-drying- application to dehydration of protein solutions” PepTalk Conference 2016, San Diego CA
Recent literature on spray-freeze drying • • •
• •
•
•
Werly, E.P., Baumann, E.K., 1964. Production of submicronized powder by spray freezing.Arch. Environ. Health 9, 567–571. S.Wanning , R.Süverkrüp, A.Lamprecht. Pharmaceutical spray freeze drying, Intern. J. of Phramaceutics, 488 (2015) 136–153 Carpenter JF, Pham BV, Randolph T, Seid R, Truong-Le V. 2003. Spray freeze dry of compositions for pulmonary administration. WO2003087339. Leuenberger H, Plitzko M, Puchkov M. 2006. Spray freeze drying in a fluidized bed at normal and low pressure. Drying Technol 24(6):711–719. Cheow WS, Ng ML, Kho K, Hadinoto K. 2011. Spray-freeze-drying production of thermally sensitive polymeric nanoparticle aggregates for inhaled drug delivery: Effect of freeze-drying adjuvants. Int J Pharm 404(1–2):289–300. Gao Y, Zhu CL, Zhang XX, Gan L, Gan Y. 2011. Lipid-polymer composite microspheres for colon-specific drug delivery prepared using an ultrasonic spray freeze-drying technique. J Microencapsul 28(6):549–556. Dolly P, Anishaparvin A, Joseph GS, Anandharamakrishnan C. 2011. Microencapsulation of Lactobacillus plantarum (mtcc 5422) by spray-freezedrying method and evaluation of survival in simulated gastrointestinal conditions. J Microencapsul 28(6):568–574
Background
Typical Limitations of conventional FD • static drying (under vacuum) offers only limited heat & mass transfer • heat transfer has to occur across frozen product • vapor flow limitations, e.g. – diffusion barrier thickness
• product inhomogeneities may occur (e.g. caking, density variations)
• product handling properties (e.g. flowability, dust)
• primary packaging requirements • production logistics 4
4 © MERIDION Technologies GmbH
Background / History:
Specific past R&D work performed Research Project at Basel School of Pharmacy (Prof. Hans Leuenberger): Atmospheric Spray Freeze Drying in Fluidized Bed Operations
• started in the mid ‘80s (in coop. with Glatt GmbH) • 3 research projects realized until the mid ‘90s
5
5 © MERIDION Technologies GmbH
Background / History:
Specific past R&D work performed Atmospheric Spray Freeze Drying in Fluidized Bed
Result of Research Work: • 3 step process required (spray freezing (air temp. < -60°C); primary drying (Tp:
