A Review on Lyophilization: A Technique to Improve Stability of Hygroscopic, Thermolabile Substances

  • A. Shivanand S.G.R.R.I.T.S
  • Sayantan Mukhopadhayaya S.G.R.R.I.T.S
Keywords: Thermolabile, Moisture sensitive, Lyophilization, Sublimation, End point detection

Abstract

The active pharmaceutical ingredient that is thermolabile and moisture sensitive in nature generally degraded in atmospheric condition and thus have reduced stability and self-life. Lyophilization is one of those techniques which is utilized effectively to improve such critical condition. It is the one of the emerging technology in themodern era, which is effectively involved in the preparation of several antibiotics (e.g., chloramphenicol, doxycycline) and anti-cancer drugs (e.g., doxorubicin, epirubicin). This technique effectively utilized the phenomenon of sublimation to obtained primary dried product followed by removal of excess amount of moisture by modulation of heat. This technique not only improved self-life of thedrug but also provides fast reconstitution and reduced the cost of storage and shipping. Inthis review article principle behind lyophilization, steps involved, formulation aspects, theimportance of lyophilization and detection of the end point in lyophilization along with recent advancementwas explained.

Author Biographies

A. Shivanand, S.G.R.R.I.T.S

Division of Pharmaceutical Sciences
S.G.R.R.I.T.S,
Dehradun, Uttarakhand, India.

Sayantan Mukhopadhayaya, S.G.R.R.I.T.S

Division of Pharmaceutical Sciences
S.G.R.R.I.T.S,
Dehradun, Uttarakhand, India.

References

1. Sandip K., Rajesh K.and Mallinath H; A review on freeze drying process of pharmaceuticals; Int J Res Pharm Sci;2013; 4(1); 76-94
2. Suruchi S.V; A review on rational design to optimize stable lyophilized parenteral products; Int J Pharm Sci Rev Res;2014; 29(2);169-178
3. Girish PK., Vibha V and Sreenivasa M; Lyophilization: An emerging trend in formulation ofparenterals; IJPRS; 2014; 3(3);393-402
4. Nail SL; Fundamentals of freeze-drying Development and manufacture of protein pharmaceuticals;Marcel Dekker; 2002; 281–360.
5. Nireesha GR., Divya L and Sowmya C; Lyophilization freeze drying: A review;IJNTPS; 2013; 3(4);87-98
6. Tushar RJ and Moon RS; Review on lyophilization technique; WJPPS;2015; 4(5);1906-1928
7. Sunil R., Ashutosh B and Ritesh V; A review: The lyophilization process for the development of unstable drug;EJBPS; 2015; 2(4); 1137-1151
8. Pradnya M.K., Bhushan B and Saudagar R.B; Lyophilization Technique: A Review; Asian J. Res. Pharm. Sci;2016;6(4); 269-276
9. Chang B.S and Patro S.Y; Freeze-drying process development for protein pharmaceuticals Lyophilization of Biopharmaceuticals;AAPS; 2004; 113-138
10. Xiaolin T and Michael J.P; Design of freeze-drying processes for pharmaceuticals practicaladvice;Pharm Res;2004; 21(2); 191-200
11. Frank Kofi BA; Understanding lyophilization formulation development; Pharm. Tec; 2004; 20; 10-18
12. Bisht D and Zeenat I; Lyophilization Process and optimization for pharmaceuticals;IJDRA;2015; 3(1);30-40
13. Lippincolt and Williams K; Remington thescience & practice of pharmacy Parenteral preparation; ISE publication; 2000; 1; 804-819
14. Kasper JC and Friess W; The freezing step in lyophilization: physico-chemical fundamentals, freezing methods and consequences on process performance and quality attributes of biopharmaceuticals; Eur. J. Pharm. Biopharm;2011; 78(2);248-263
15. Avis KE., Lieberman HA and Lachman L; Pharmaceutical dosage forms Parenteral medications; Marcel Dekker; 1993.
16. Searles JA., Carpenter JF and Randolph TW; The ice nucleation temperature determines the primary drying rate of lyophilization for samples frozen on a temperature controlled shelf;J. Pharm. Sci;2001; 90(7);860-71
17. Searles JA., Carpenter JF and Randolph TW; Annealing to optimize the primary drying rate, reduce freezing-induced drying rate heterogeneity, and determine Tg′ in pharmaceutical lyophilization; J. Pharm. Sci; 2001; 90(7); 872-887
18. Hawe A and Friess W; Physicochemical characterization of the freezing behavior of mannitol-human serum albumin formulations;AAPS; 2006; 7(4); 85-94
19. Lian Y., Nathaniel M and Edward G.G; Existence of a mannitol hydrate during freeze-drying and practical implications;J. Pharm. Sci;1999;88(2);196-198
20. SadikogluH., Liapis A. I and CrosserO. K; Optimal control of the primary and secondary drying stages of bulk solution freeze drying in trays, drying technology; An International Journal; 1998; 16(5); 399-431
21. Sajal M.P., Takayuki D and Michael J.P; Determination of end point of primary drying in freeze-drying process control; AAPS; 2010; 11(1); 73-84
22. William J.K., Michael F and Steven J.D; Evaluation of tunable diode laser absorption spectroscopy for in‐process water vapor mass flux measurements during freeze drying;J. Pharm. Sci;2007; 96(7); 1776-1793
23. Y. M and R.V; Freeze-drying process monitoring using a cold plasma ionization device;PDA J Pharm Sci Technol; 2007;61; 160-174
24. Koustuv C., Evgenyi Y.S and Raj S; Partially crystalline systems in lyophilization II withstanding collapse at high primary drying temperatures and impact on protein activity recovery;J. Pharm. Sci; 2005; 94; 809-820
25. Wallen AJ., Van Ocker SH and Sinacola JR; The effect of loading process on product collapse during large-scale lyophilization;J. Pharm. Sci;2009; 98(3); 997-1004
26. Chang BS., Beauvais RM and Carpenter JF; Physical factors affecting the storage stability of freeze-dried interleukin-1 receptor antagonist: glass transition and protein conformation; Arch. Biochem. Biophys; 1996; 331(2); 249-58
27. Bardat A; Moisture measurement a new method for monitoring freeze-drying cycles; J Parenter Sci Techno; 1993; 47(6); 293-299
28. Wei W; Lyophilization and development of solid protein pharmaceuticals; Int. J. Pharm; 2000; 203; 1-60
29. Sunil R and Ashutosh B; The lyophilization process for the development of unstable doxorubicin injectable formulation;IAJPS;2015;2(9); 1339-1347
30. Mikkilineni R., Srinivasa P.B and Mandava V.B.R; Formulation and evaluation of stable lyophilized bendamustine hydrochloride injection; Int J Pharm Sci Rev Res; 2013;23(2); 89-93
31. Neema S., Washkuhn RJ and Brendel RJ; Excipients and their use in Injectable products; PDA J Pharm Sci Technol; 1997; 51; 166-171
32. Shah N.V., Solanki H and Prajapati V; Impact of formulation ingredients on qualityof the parenteral products; WJPPS; 2015; 4(3); 468-482
33. Shah R and Mehta P; Freeze dried injectable drug product development selection of non-functional additives; Int J Pharm Pharm Sci;2014; 6(9): 3-7
34. Shireesh P.A and Sydney O.U; A review and classification of emerging excipients in parenteral medications;Pharm Tech; 2003; 46-60
35. Nema S and Brendel RJ; Excipients and their role in approved injectable products current usage and future directions; PDA J Pharm Sci Technol; 2011; 65(3); 287-332
36. Sougata P., Deepak S and Vikas C; Excipient selection in parenteral formulation development; Pharma Times;2013; 45(3);65-77
37. Yasir M and Umer F; Excipients use in parenteral and lyophilized formulation development; Open science journal of pharmacy and pharmacology; 2015; 3(3); 19-27
38. Ankit B., Lokesh K and Arvind K.B; Excipients used in lyophilization of small molecules; J. Excipients and Food Chem; 2010; 1(1); 41-54
39. Freeze Drying / Lyophilization Information: Basic Principles [Internet]. Spscientific.com. 2017 [cited 10 June 2017]. Available from: https://www.spscientific.com/freeze-drying-lyophilization-basics
40. Pharmaceutical Freeze Drying: The Lyophilization Process [Internet]. 2010 [cited 10 June 2017]. Available from: https://www.ispe.org/great-lakes/milton-lyophilizatio-2010-presentation.pdf
Published
2017-11-01
How to Cite
[1]
Shivanand, A. and Mukhopadhayaya, S. 2017. A Review on Lyophilization: A Technique to Improve Stability of Hygroscopic, Thermolabile Substances. PharmaTutor. 5, 11 (Nov. 2017), 28-39.