Liyofilizasyon: Genel Proses Değerlendirmesi

Yıl 2018, Cilt: 29 Sayı: 1, 62 - 69, 01.07.2018

Mustafa Sencer Karagül Buket Altuntaş

https://doi.org/10.35864/evmd.513002

Cited By: 4

Öz

Liyofilizasyon veya bir diğer adıyla dondurarak kurutma, final ürün özelliklerini, stabiliteyi ve verimi etkileyen kompleks bir proses olarak kabul edilmektedir. Liyofilizasyon, zorluklarına rağmen sunduğu avantajlar nedeniyle zoonoz hastalıkların da yer aldığı birçok hastalığa karşı uygulanan aşıların üretim zincirinde yer almaktadır. Aşılar diğer biyolojik maddeler veya mikroorganizmalar liyofilizasyon dışında, soğutma veya dondurma ile stabil hale getirilebilirler. Fakat ürünlerin donmuş fazda taşınması ve depolanmasının yüksek maliyeti yanında olası sistemsel arızalar ürünün yapısını bozarak kaybına neden olabilmektedir. Bu açıdan liyofilize formulasyonlar daha iyi stabilite avantajı ile birlikte, taşıma ve depolama sırasında da kolay idare sağlamaktadırlar. Bu derlemede, liyofilizasyon metodunun genel proses değerlendirilmesi yapılarak, prosesi oluşturan, dondurma, birincil kurutma ve ikincil kurutma basamakları arasındaki etkileşim açıklanmıştır. Canlı aşıların üretiminde önemli bir proses olan liyofilizasyon, prosesi uygulayan araştırmacıların gözünden değerlendirilmiş, üretim ve liyofilizasyon faaliyetlerinde bulunan çalışanlara yönlendirici ve destekleyici bilgiler paylaşılmıştır.

Anahtar Kelimeler

Dondurma, Dondurarak-Kurutma, Liyofilizasyon, Stabilite

Kaynakça

• 1. Adams GDJ, Cook I, Ward KR, (2015). The Principles of Freeze-Drying. Wolkers WF, Oldenhof H. eds. Cryopreservation and Freeze-Drying Protocols. Springer, New York. p. 121-143.
• 2. Akyurt M, Zaki G, Habeebullah B, (2002). Freezing phenomena in ice–water systems. Energy Convers. Manag. 43, 1773–1789.
• 3. Anonim, (2017). A guide to freze drying for the laboratory. An industry service publication. Labconco, Erişim adresi: http://www.thermofishersci.in/lit/Labconco%20-%20 A%20laboratory%20guide%20to%20freeze%20drying. pdf. Erişim tarihi: 15.04.2018.
• 4. Carpenter JF, Pikal MJ,. Chang BS,. Randolph TW, (1997). Rational Desgin of Stable Lyophilized Protein formulatinos: Some Practical Advice. Pharm. Res. 14(8), 969-975.
• 5. Ciurzyńska A, Lenart A, (2011). Freeze-Drying – Application in Food Processing and Biotechnology – A Review. Pol. J. Food Nutr. Sci. 61(3), 165-171.
• 6. Cook I, (2018). Why, What and How? Understanding the freeze drying process Biopharma Technology Ltd. Erişim adresi: http://www.biopharma.co.uk/wp-content/ uploads/2010/07/Why_What_How.pdf. Erişim tarihi: 15.04.2018.
• 7. Deepak B, Iqbal Z, (2015). Lyophilization - Process and Opitimization for Pharmaceuticals. IJDRA, 3(1), 30-40.
• 8. Franks F, (1998). Freeze-drying of bioproducts: putting principles into practice, Eur. J. Pharm. Biopharm. 45, 221–229.
• 9. Franks F, (2007). Freeze-drying of pharmaceuticals and biopharmaceuticals, Cambridge: RSC Publishing, The Royal Society of Chemistry.
• 10. Gaidhani KA, Harwalkar M, Bhambere D, Nirgude PS, (2015). Lyophilization / Freeze Drying – A Review. WJPR. 4(8), 516-543.
• 11. Halkman A, Doğan, HB, (2000). Gıda Mikrobiyolojisi ve Uygulamaları. Genişletilmiş 2. Baskı, Ankara Üniversitesi Ziraat Fakültesi Gıda Mühendisliği Bölümü Yayını. Sim Matbaası, Ankara.
• 12. Horn J, Friess W, (2018). Detection of Collapse and Crystallization of Saccharide, Protein, and Mannitol Formulations by Optical Fibers in Lyophilization. Front Chem. doi: 10.3389/fchem.2018.00004.
• 13. Jennigs TA, (2008). Lyophilization, introduction and basic principles. New York: Informa Healthcare.
• 14. Jiang S, Nail SL, (1998). Effect of process conditions on recovery of protein activity after freezing and freeze-drying. Eur J Pharm Biopharm. 45, 249–257.
• 15. John G. Day, Glyn N. Stacey eds., (2007) Cryopreservation and Freeze-Drying Protocols, Second Edition, New Jersey, Humana Press Inc.
• 16. Kasper JC, Friess W, (2011). The freezing step in lyophilization: Physico-chemical fundamentals, freezing methods and consequences on process performance and quality attributes of biopharmaceuticals. Eur J Pharm Biopharm. 78, 243-268.
• 17. Khairnar S, Kini R, Harwalkar M, Salunkhe K, Chaudhari SR, (2013). A review on freeze drying process of pharmaceuticals, IJRPS. 4(1), 76 – 94.
• 18. Matejschuk P, Stanley M, Jefferson P, (2010). Freeze-Drying of biological standards. Rey L, May JC. eds. Freze Drying/ Lyophilisation of Pharmaceutical and Biological Products. Third edition. Informa Healthcare, London. p.317-353.
• 19. Meister E, Gieseler H, (2008). A significant comparison between collapse and glass transition temperatures. European Pharmaceutical Review. 5. Erişim adresi: https:// www.europeanpharmaceuticalreview.com/article/1479/aKaragül MS ve Altuntaş B. Genel Proses Değerlendirmesi 69 significant-comparison-between-collapse-and-glass-transition- temperatures/ . Erişim tarihi: 15.04.2018.
• 20. Morgan CA, Herman N, White PA, Vesey G, (2006). Preservation of micro-organisms by drying; A review. J Microbiol Methods. 66(2), 183–193.
• 21. Oetjen GW, (1999). Freeze drying. Germany: Wiley VCH.
• 22. Patapoff TW, Overcashier DE, (2002). The importance of freezing on lyophilization cycle development. Biopharm. 16-21.
• 23. Patel SM, Doen T, Pikal MJ, (2009). Determination of end point of primary drying in freeze-drying process control. AAPS Pharm Sci Tech, 11(1), DOI: 10.1208/s12249-009- 9362-7
• 24. Przic DS, Ruzic NLJ, Petrovic, SD, (2004). Lyophilizationthe process and industrial use. Chem. Ind. 58(12), 552-562.
• 25. Ratti C, (2012). Freeze - drying Process Design. Jasim A, Mohammad Shafiur R. eds. Handbook of Food Process Design, First Edition. Blackwell Publishing Ltd. New Jersey. p. 621-647.
• 26. Rey L, (2010). Glimpses into the realm of freeze-drying classical issues and new ventures. Rey L, May JC. eds. Freze Drying/Lyophilisation of Pharmaceutical and Biological Products. Third edition, Informa Healthcare, London. p.1-28.
• 27. Ross C, Gaster T, Ward K, (2008). Biopharma Technology Limited. The importance of critical temperatures in the freeze drying of pharmaceautical products. Erişim adresi:http://www.biopharma.co.uk/wp-content/uploads/ 2010/07/importance_critical_temps.pdf. Erişim tarihi: 15.04.2018.
• 28. Roy I, Gupta MN, (2004). Freeze-drying of proteins: some emerging concerns. Biotechnol Appl Biochem. 39(2), 165- 77.
• 29. Searless JA, Carpenter JF, 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.
• 30. Searless JA, (2010). Freezing and anneling phenomena in lyophilization, Rey L, May JC. eds. Freze Drying/Lyophilisation of Pharmaceutical and Biological Products. Third edition, Informa Healthcare, London p.52-81.
• 31. Tang XC, Pikal MJ, (2004). Design of freeze-drying processes for pharmaceuticals: Practical advice. Pharm. Res. 21(2), 191-200.
• 32. Tsinontides SC, Rajniak P, Pham D, Hunke WA, Placek J, Reynolds SD, (2008). Freeze drying—principles and practice for successful scale-up to manufacturing. Int J Pharm. 280, 1–16.