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2015, Number 1

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Biotecnol Apl 2015; 32 (1)

Design of the lyophilization process of a L-leucyl-L-alanine dipeptide formulation based on its thermal properties

Sánchez-González A, Hernández-González GR

Language: English
References: 28
Page: 1221-1225
PDF size: 477.20 Kb.


ABSTRACT

The system for phenylketonuria diagnostic in newborns (UMTEST® PKU) is produced at the Center for Immunoassay (Havana, Cuba). L-leucyl-L-alanine is one of the kit components and requires lyophilization due to its limited aqueous solution stability. Results from Diffferential Thermal Analysis/Impedance (DTA/ Zsinφ) and lyomicroscopy determinations, identify that during the freezing step product temperature must be below –30 ºC, while throughout the primary drying process product temperature at sublimation front cannot exceed –18.9 ºC. The use of a procedure based on the critical variables determinations, allow the lyophilization of three industrial batches that finally fulfilled the quality specifications and achieve a reduction of 32 % in the cycle total time.


REFERENCES

  1. Kaye CI; the Committee on Genetics. Newborn Screening Fact Sheets. Pediatrics 2006;118:e934-63.

  2. Arneson W, Brickell J. Clinical Chemistry: A Laboratory Perspective. Philadelphia: F. A. Davis Co.; 2007.

  3. Moyle JJ, Fox AM, Arthur M, Bynevelt M, Burnett JR. Meta-analysis of neuropsychological symptoms of adolescents and adults with PKU. Neuropsychol Rev. 2007;17(2):91-101.

  4. Mei JV, Alexander JR, Adam BW, Hannon WH. Use of filter paper for the collection and analysis of human whole blood specimens. J Nutr. 2001;131(5):1631S-6S.

  5. Martínez L, Robaina Z, García S, Guti- érrez E. The Cuban program for neonatal screening of phenylketonuria. Twenty years of experience: the clinical and social attention. Rev Cubana Genet Comunit. 2008;2:45-51.

  6. Gonzalez EC, Marrero N, Perez PL, Frometa A, Zulueta O, Herrera D, et al. An enzyme immunoassay for determining 17alpha-hydroxyprogesterone in dried blood spots on filter paper using an ultramicroanalytical system. Clin Chim Acta. 2008;394(1-2):63-6.

  7. Pikal MJ. Freeze drying. In: Swarbrick J, editor. Encyclopedia of Pharmaceutical Technology. New York: Informa Healthcare; 2007; p. 1807-33.

  8. Tang X, Pikal MJ. Design of freeze-drying processes for pharmaceuticals: practical advice. Pharm Res. 2004;21(2):191-200.

  9. Matejschuk P, Malik K, Duru C, Bristow A. Freeze drying of biologicals: process development to ensure biostability. Amer Pharm Rev 2009;12(2):12-7.

  10. Rey L, May JC. Freeze-Drying/Lyophilization of Pharmaceutical and Biological Products. New York: Marcel Dekker; 2004.

  11. Searles JA, Nail SL. Elements of quality design in development and scale-up of freeze dried parenterals. Biopharm Int. 2008;21(1):44-52.

  12. Kasper JC, Winter G, Friess W. Recent advances and further challenges in lyophilization. Eur J Pharm Biopharm. 2013;85(2):162-9.

  13. Bosca S, Barresi AA, Fissore D. Fast freeze-drying cycle design and optimization using a PAT based on the measurement of product temperature. Eur J Pharm Biopharm. 2013;85(2):253-62.

  14. Geidobler R, Winter G. Controlled ice nucleation in the field of freeze-drying: fundamentals and technology review. Eur J Pharm Biopharm. 2013;85(2):214-22.

  15. Tang XC, Nail SL, Pikal MJ. Evaluation of manometric temperature measurement, a process analytical technology tool for freeze-drying: part II measurement of dry-layer resistance. AAPS PharmSciTech. 2006;7(4):93.

  16. Fissore D, Galan M, Pisano R, Velardi S, Barresi A. PAT Tools for the Optimization of the freeze-drying process. Pharm Eng. 2009;29(5):58-68.

  17. Awotwe-Otoo D, Agarabi C, Wu GK, Casey E, Read E, Lute S. Quality by design : Impact of formulation variables and their interactions on quality attributes of a lyophilized monoclonal antibody. Int J Pharm. 2012;438:167-75.

  18. Meister E, Gieseler H. Freeze-dry microscopy of protein/sugar mixtures: drying behavior, interpretation of collapse temperatures and a comparison to corresponding glass transition data. J Pharm Sci. 2009;98(9):3072-87.

  19. Schersch KB. Effect of collapse on pharmaceutical protein liophilizates [PhD Thesis]. Munich, Germany: Ludwig-Maximilians University; 2009.

  20. Shalaev EY, Johnson-Elton TD, Chang L, Pikal MJ. Thermophysical properties of pharmaceutically compatible buffers at sub-zero temperatures: implications for freeze-drying. Pharm Res. 2002;19(2):195-201.

  21. Hajare AA, More HN, Walekar PS, Hajare DA. Optimization of freeze drying cycle protocol using real time microscopy and integrated differential thermal analysis-electrical impedance. Res J Pharm Tech. 2012;5(7):985-91.

  22. Jenning TA. Lyophilization Seminar. La Habana: Phase Technologies Inc.; 2003.

  23. Rutzinger S. Freeze Drying Microscopy: Introduction and Relevance for Process Design. Erlangen: University of Erlangen-Numberg; 2009.

  24. Ma X, Wang DQ, Bouffard R, MacKenzie A. Characterization of murine monoclonal antibody to tumor necrosis factor (TNF-MAb) formulation for freeze-drying cycle development. Pharm Res. 2001;18(2):196-202.

  25. Pikal MJ, Tang X, Nail SL, inventors; University of Connecticut, Assignee. Automated process control using manometric temperature measurement. United States Patent US 6,971,187 B1; 2005 Dec.

  26. Rambhatla S, Ramot R, Bhugra C, Pikal MJ. Heat and mass transfer scale-up issues during freeze drying: II. Control and characterization

  27. of the degree of supercooling. AAPS PharmSciTech. 2004;5(4):e58.

  28. 27.Kasper CJ. Lyophilization of Nucleic Acid Nanoparticles. Formulation development, stabilization mechanisms, process monitoring [PhD Thesis]. Munich, Germany: Ludwig-Maximilians University; 2012.




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