Lyophilisation of protein-based drugs

Česká verze

Authors: Andrej Murányi; Mária Vitková
Authors place of work: Univerzita Komenského v Bratislave, Farmaceutická fakulta ; hameln rds a. s.
Published in the journal: Čes. slov. Farm., 2014; 63, 199-205
Category: Přehledy a odborná sdělení

Summary

Lyophilisation is a well-established method for drying of various substances with a wide range of applications in the pharmaceutical area. During the last decade its relevance increases with a number of therapeutically used proteins. A sensitive protein drug may undergo several changes, like unfolding and loss of activity due to various stresses during the lyophilisation process. Understanding of these processes (freezing, primary drying, secondary drying) is fundamental for manufacturing of a drug product with desired properties, namely its safety and efficacy. In order to reduce costs and increase the quality, new technologies are being rapidly developed and established in industrial lyophilisation (e.g. process analytical technologies, control nucleation techniques).

Keywords:
lyophilisation • freeze-drying • proteins • process analytical technologies

Zdroje

1. Ho R. J. Y. Biotechnology and Biopharmaceuticals: Transforming protein and Genes into Drugs. 2. vyd. Hoboken, NJ: John Wiley & Sons 2003.

2. Global Protein Therapeutics Market Outlook 2018. Dublin: Research and Markets 2014.

3. Hasset K. J., Cousins M. C., Rabia L. A., Chadwick C. M., O’Hara J. M., Nandi P., Brey R. N., Mantis N. J., Carpnter J. F., Randolph T. W. Stabilization of a recombinant ricin toxin A subunit vaccine through lyophilization. Eur J. Pharm. Biopharm. 2013; 85(2), 279–286.

4. Borde A., Larsson A., Holmgren J., Nygren E. Preparation and evaluation of a freeze-dried oral killed cholera vaccine formulation. Eur. J. Pharm. Biopharm. 2011; 79(3), 505–518.

5. Mohammed-Saeid W., Michel D., El-Anned A., Verrall R. E., Low N. H., Badea I. Development of lyophilized gemini surfactant-based gene delivery systems: influence of lyophilization on the structure, activity and stability of the lipoplexes. J. Pharm. Pharm. Sci. 2012; 15(4), 548–567.

6. Kasper J. C., Schaffert D., Ogris M., Wagner E., Friess W. Development of a lyophilized plasmid/LPEI polyplex formulation with long-term stability-a step closer from promising technology to application. J. Controlled Release 2011; 151, 246–255.

7. Abdelwahed W., Degobert G., Stainmasse S., Fessi H. Freeze-drying of nanoparticles: formulation, process and storage considerations. Adv. Drug. Delivery Rev. 2006; 58, 1688–1713.

8. Kaialy W., Nokhodchi A. Freeze-dried mannitol for superior pulmonary drug delivery via dry powder inhaler. Pharm. Res. 2013; 30(2), 458–477.

9. Oliveira J. M., Rodrigues M. T., Silva S. S., Malafaya P. B., Gomes M. E. Viegas C. A., Dias I. R., Azevedo J. T., Mano J. F., Reis, R. L. Novel hydroxyapatite/chitosan bilayered scaffold for osteochondral tissue-engineering applications: Scaffold design and its performance when seeded with goat bone marrow stromal cells. Biomaterials 2006; 27, 6123–6137.

10. Labovitiadi O., Lamb A. J., Matthews K. H. In vitro efficacy of antimicrobial wafers against methicillin-resistant Staphylococcus aureus. Ther. Deliv. 2012; 3(4), 443–455.

11. Ayensu I., Mitchell J. C., Boateng J. S. Development and physico-mechanical characterisation of lyophilised chitosan wafers as potential protein drug delivery systems via the buccal mucosa. Colloids Surf. B. Biointerfaces 2012; 1(91), 258–265.

12. Vasconcelos T., Sarmento B., Costa P. Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug. Discov. Today 2007; 12(23–24), 1068–1075.

13. De Waard H., Hinrichs W. L. J., Frijlink H. W. A novel bottom-up process to produce drug nanocrystals: Controlled crystallization during freeze-drying. J. Control. Release 2008; 128(2), 179–183.

14. Franks F. Freeze-drying of Pharmaceuticals and Biopharmaceuticals. Cambridge: RSC Publishning 2007.

15. Milton N., Pikal M. J., Roy M. L., Nail S. T. Evaluation of manometric temperature measurement as a method of monitoring product temperature during lyophilization. PDA J. Pharm. Sci. Technol. 1997; 51(1), 7–16.

16. Pikal M. J., Roy M. L., Shah S. Mass and heat transfer in vial freeze-drying of pharmaceuticals: role of the vial. J. Pharm. Sci. 1984; 73(9), 1224–1237.

17. Pikal M. J. Freeze Drying. In Encyclopedia of Pharmaceutical Technology. 2nd ed. Ed Swabrick, J. Boylan, J.C. New York: Marcel Dekker 2002.

18. Searles J. A., Carpenter J. F., Randolph T. W. 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), 860–871.

19. Patapoff T. W., Overcashler D. E. The importance of freezing on lyophilization cycle development. BioPharm. 2002; 15(3), 16–21.

20. Bursac R., Sever R., Hunek B. A practical method for resolving the nucleation problem in lyophilization. BioProcess Int. 2009; 7(9), 66–72.

21. Franks F. Freeze-drying: from empiricism to predictability. The significance of glass transitions. Dev. Biol. Stand. 1992; 74, 9–18; disccusion 19.

22. Gatlin L. A., Nail S. L. Protein purification process engineering. Freeze drying: A practical overview. Bioprocess Technol. 1994; 18, 317–367.

23. Chang B. S., Kedrick B. S., Carpenter J. F. Surface-induced denaturation of proteins during freezing and its inhibition by surfactants. J. Pharm. Sci. 1996; 85(12), 1325–1330.

24. Pikal M. J., Shah S., Roy M. L., Putman R. The secondary drying stage of freeze-drying: drying kinetics as a function of temperature and chamber pressure. Int. J. Pharm. 1990; 60(3), 203–207.

25. Rambhatla S., Ramot R., Bhugra C., Pikal M. J. Heat and mass transfer scale-up issues during freeze-drying: II. Control of characterization of the degree of supercooling. AAPS Pharm. Sci. Tech. 2004; 5(4), 1–8.

26. Franks F. Freeze-drying of bioproducts: putting principles into practice. Eur. J. Pharm. Biopharm. 1998; 45, 221–229.

27. Konstantinidis A. K., Kuu W., Otten L., Nail S. L., Sever R. R. Controlled nucleation in freeze-drying: Effects on pore size in the dried product layer, mass transfer resistance, and primary drying rate. J. Pharm. Sci. 2011; 100(8), 3453–3470.

28. Geidobler R., Konrad I., Winter G. Can controlled ice nucleation improve freeze-drying of highly-concentrated protein formulations? J. Pharm. Sci. 2013; 102(11), 3915–3919.

29. Geidobler R., Mannschedel S., Winter G. A new approach to achieve controlled ice nucleation of supercooled solution during the freezing step in freeze-drying. 2012; 101(12), 4409–4413.

30. Searles J. A., Carpenter J. F., Randolph T. W. Annealing to optimize the primary drying rate, reduce freeze-induced drying rate heterogenity, and determine T(g)´ in pharmaceutical lyophilization. J. Pharm. Sci. 2001; 90(7), 872–887.

31. Tang X., Pikal M. J. Design of freeze-drying processes for pharmaceuticals: Practical advice. Pharm. Res. 2004; 21(2), 191–200.

32. Pikal M. J. Freeze-drying of proteins. Part I.: Process Design. Bio.Pharm. 1990; 3, 18–27.

33. Pikal M. J., Shah S. The collapse temperature in freeze-drying: dependence on measurement methodology and rate of water removal from the glassy phase. In. J. Pharm. 1990; 62, 165–186.

34. Schersch K., Betz O., Garidel P., Muehlau S., Bassarab S., Winter G. Systematic investigation of the effect of lyophilizate collapse on the pharmaceutically relevant proteins I: Stability after freeze-drying. J. Pharm. Sci. 2010; 99(5), 2256–2277.

35. Schersch K., Betz O., Garidel P., Muehlau S., Bassarab S., Winter G. Systematic investigation of the effect of lyophilizate collapse on the pharmaceutically relevant proteins, part 2: Stability during storage at elevated temperatures. J. Pharm. Sci. 2012; 101(7), 2288–2306.

36. Kasraian K., Spitznagel T. M., Juneau J. A., Yim K. Characterization of the sucrose/glycine/water system by differential scanning calorimetry and freeze-drying microscopy. Pharm. Dev. Technol. 1998; 3(2): 233–239.

37. Beirowski J., Geiseler H. Application of DSC and MDSC in the development of freeze dried pharmaceuticals. Eur. Pharm. Rev. 2008; 6, 63–70.

38. Hajare A. A., More H. N., Walekar P. S., Hajare D. A. Optimization of Freeze Drying Cycle Protocol Using Real Time Microscopy and Integrated Differential Thermal Analysis-Electrical Impedance. Res. J. Pharm. Tech. 2012; 5(7), 985–991.

39. Nail S. L., Her L. M. Proffitt C. P. Nail L. L. An inproved microscope stage for direct observation of freezing and freeze drying. Pharm. Res. 1994; 11(8), 1098–1100.

40. Pikal M. J., Lang J. E. Rubber closures as a source of haze in freeze dried parenterals: Test methodology for closure evaluation. J. Parent. Drug. Assoc. 1978; 32, 162–173.

41. Wang W. Lyophilisation and development of solid protein pharmaceuticals. Int. J. Pharm. 2000; 203, 1–60.

42. Patel S. M., Doen T., Pikal M. J. Determination of end point of primary drying in freeze-drying process control. AAPS Pharm. Sci.Tech. 2009; 11(1), 73–84.

43. Hsu C. C., Ward C. A., Pearlman R., Nguyen H. M., Yeung D. A., Curley J. G. Determining the optimum residual moisture in lyophilized protein pharmaceuticals. Dev. Biol. Stand. 1992; 74, 255–270, discussion 271.

44. Pikal M. J., Dellerman K. M., Roy M. L., Riggin R. M. The effects of formulation variables on the stability of freeze-dried human growth hormone. Pharm Res. 1991; 8(4), 427–436.

45. Breen E. D., Curley J. G., Overcashier D. E., Hsu C. C., Shire S. J. Effect of moisture on the stability of a lyophilized humanized monoclonal antibody formulation. Pharm Res. 2001; 18(9), 1345–1353.

46. Sarciaux J. M., Hageman M. J. Effects of bovine somatotropin (rbSt) concentration at different moisture levels on the physical stability of sucrose in freeze-dried rbSt/sucrose mixtures. J Pharm Sci. 1997; 86(3), 365–371.

47. Pikal M. J., Shah S. Moisture transfer from stopper to product and resulting stability implications. Dev. Biol. Stand. 1992; 74, 165–177.

48. Donovan P. D., Corvari V., Burton M. D., Rajagopalan N. Effect of stopper processing conditions on moisture content and ramifications for lyophilized products: Comparison of “Low” and “High” moisture uptake stoppers. PDA J. Pharm. Sci. Tech. 2007; 61(1), 51–58.

49. Schneid S., Geiseler H., Kessler W. J., Luthra S. A., Pikal M. J. Optimization of secondary drying step in freeze drying using TDLAS technology. AAPS PharmSciTech. 2011; 12(1), 379–387.

50. Graziano G., Catanzano F., Riccio A., Barone G. A reassesment of the molecular origin of cold denaturation. J. Biochem. 1997; 122, 395–401.

51. Koseki T., Kitabatake N., Doi E. Freezing denaturation of ovalbumin at acid pH. J. Biochem. 1990; 107, 389–394.

52. Jaenicke R. Protein structure and function at low temperatures. Philos. Trans. R. Soc. Lond. B Biol. Sci. 1990; 326, 535–551.

53. Pikal-Cleland K. A., Carpenter J. F. Lyophilization-induced protein denaturation in phosphate buffer systems: monomeric and tetrameric beta-galactosidase. J. Pharm. Sci. 2001; 90(9), 1255–1268.

54. Sundaramurthi P., Suryanarayanan R. The effect of crystallizing and non-crystallizing cosolutes on succinate buffer crystallization and the consequent pH shift in frozen solutions. Pharm Res. 2011; 28(2), 374–385.

55. Strambini G. B., Gabellieri E. Proteins in frozen solutions: evidence of ice-induced partial unfolding. Biophys. J. 1996; 70, 971–976.

56. Chang B. S., Kendrick B. S., Carpenter J. F. Surface-induced denaturation of proteins during freezing and its inhibition by surfactants. J. Pharm. Sci. 1996; 85(12), 1325–1330.

57. Rupley J. A., Careri G. Protein hydration and function. Adv. Protein. Chem. 1991; 41: 37–173.

58. Prestrelski S. J., Tedeschi N., Arakawa T., Carpenter J. F. Dehydration-induced conformational transitions in proteins and their inhibition by stabilizers. Biophys. J. 1993; 65, 661–671.

59. Franks F., Hatley H. M., Mathias S. F. Material science and production of shelf-stable biologicals. Biopharm. 1991; 4, 38–55.

60. Cicerone M. T., Douglas J. F. ββ-relaxation governs protein stability in sugar-glass matrices. Soft Matter 2012; 8, 29831991.

61. Bhatnagar B. S., Bogner R. H., Pikal M. J. Protein stability during freezing: separation of stresses and mechanisms of protein stabilization. Pharm. Dev. Technol. 2007; 12(5), 505–523.

62. Remmele R. L., Krishnan S., Callahan W. J. Development of lyophilized protein drug products. Curr. Pharm. Biotechnol. 2012; 13(3), 471–496.

63. Chang L., Pikal M. J. Mechanisms of protein stabilization in the solid state. J. Pharm. Sci. 2009; 98(9); 2886–2908.

64. Mockus L., LeBlond D., Basu P. K., Shah R. B., Khan M. A. A QbD Case Study: Bayesian Prediction of Lyophilization Cycle Parameters. AAPS PharmSciTech. 2011; 12(1), 442–448.

65. Patel S. M., Pikal M. J. Lyophilization Process Design Space. J. Pharm. Sci. 2013; 1052(11), 3883–3887.

66. ICH Guideline Q8(R2) Pharmaceutical Development, http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q8_R1/Step4/Q8_R2_Guideline.pdf (10. 02. 2014).

67. Schneid S., Geiseler H. Evaluation of a new wireless temperature remote interoggation system (TEMPRIS) to measure product temperature during freeze-drying. AAPS PharmSciTech. 2008; 9, 729–739.

68. Kasper J. C., Wiggenhorn M., Resch M., Friess W. Implementation and evaluation of an optical fiber system as novel process monitoring tool during lyophilizaion. Eur. J. Pharm. Biopharm. 2013; 83, 449–459.

69. De Beer T. R., Vercruysse P., Burgraevve A., Quinten T., Ouyang J., Zhang X., Vervaet C., Remon J. P., Baeyens W. R. In-line and real-time process monitoring of a freeze drying process using Raman and NIR spectroscopy as complementary process analytical technology (PAT) tools. J. Pharm. Sci. 2009; 98(9), 3430–3446.

70. Hibler S., Wagner C., Geiseler H. Vial freeze-drying, part 1: new insights into heat transfer characteristics of tubing and moulded vials. J. Pharm. Sci. 2012; 101(3), 1189–1201.