Freeze-Drying Process Optimization for a Small Molecule - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

Freeze-Drying Process Optimization for a Small Molecule
The authors evaluate the thermal properties of gentamicin sulfate as a small-molecule drug model in optimizing the freeze-drying cycle.


Pharmaceutical Technology
Volume 36, Issue 6, pp. 48-52

Conclusion

The results of this study show that even for the relatively simple solution of a pure small-molecule drug, the collapse temperature determined by FDM can be considered as the practically more relevant CFT for process development and optimization. The direct observation of the collapse event and the width of the gap between Toc and Tfc can provide additional valuable information on the temperature tolerance of the sample. In the case of gentamicin sulfate, the temperature difference is not as big as it has been reported for protein formulations, indicating low robustness of the dried material in the microcollapse regime. Considering the great influence of small differences in product temperature on primary drying time and product morphology, the use of freeze-dry microscopy is a substantial contribution to efficiency and quality in the freeze-drying of small molecules.

Click here for video on the process of taking freeze-dry microscopic measurements

Acknowledgments

The authors acknowledge Hiltrud Lindenblatt, PhD, and senior scientist of life-cycle management CMC management at Merck KGaA, for providing the gentamicin sulfate.

Henning Gieseler* is an assistant professor and group leader in the Freeze-Drying Focus Group, Division of Pharmaceutics, University of Erlangen (Erlangen, Germany), and managing director of Gilyos GmbH, 15 Friedrich-Bergius-Ring, Wuerzburg, Germany, 97076, tel. +49 931 907 05678,
Susanne Hibler is a graduate student in the Freeze-Drying Focus Group, Division of Pharmaceutics, University of Erlangen.

References

1. S. Rambhatla and M.J. Pikal, "Heat and Mass Transfer Issues in Freeze-drying Process Development," in Lyophilization of Biopharmaceuticals, H. R. Constantino and M.J. Pikal, Eds. (American Association of Pharmaceutical Scientists, Arlington, 1st ed., 2004), pp 75–109.

2. X. Tang and M.J. Pikal, Pharm. Res. 21 (2), 191–200 (2004).

3. M.J. Pikal and S. Shah, Int. J. Pharm. 62 (2–3), 165–186 (1990).

4. J.F. Carpenter et al., Pharm. Res. 14 (8), 969–975 (1997).

5. R.E. Johnson et al., J. Pharm. Sci. 99 (6), 2863–2873 (2010).

6. D.E. Overcashier, T.W. Patapoff, and C.C. Hsu, J. Pharm. Sci. 88 (7), 688–695 (1999).

7. J.D. Colandene et al. J. Pharm. Sci. 96 (6), 1598–1608 (2007).

8. E. Meister and H. Gieseler, J. Pharm. Sci. 98 (9), 3072–3087 (2009).

9. L.M. Her and S.L. Nail, Pharm. Res. 11 (1), 54–59 (1994).

10. J. Liu, Pharm. Dev. Technol. 11 (1), 3–28 (2006).

11. E. Meister, Methodology, Data Interpretation and Practical Transfer of Freeze-Dry Microscopy, PhD. Thesis, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (2009).

12. F. Fonseca et al., Biotechnol. Prog. 20 (1), 229–238 (2004).

13. M.J. Pikal, J. Parenter. Sci. Technol. 39 (3), 115–139 (1985).


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
FDASIA was signed into law two years ago. Where has the most progress been made in implementation?
Reducing drug shortages
Breakthrough designations
Protecting the supply chain
Expedited reviews of drug submissions
More stakeholder involvement
Reducing drug shortages
31%
Breakthrough designations
8%
Protecting the supply chain
42%
Expedited reviews of drug submissions
8%
More stakeholder involvement
12%
View Results
Jim Miller Outsourcing Outlook Jim Miller Health Systems Raise the Bar on Reimbursing New Drugs
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerThe Mainstreaming of Continuous Flow API Synthesis
Jill Wechsler Regulatory Watch Jill Wechsler Industry Seeks Clearer Standards for Track and Trace
Siegfried Schmitt Ask the Expert Siegfried SchmittData Integrity
Sandoz Wins Biosimilar Filing Race
NIH Translational Research Partnership Yields Promising Therapy
Clusters set to benefit from improved funding climate but IP rights are even more critical
Supplier Audit Program Marks Progress
FDA, Drug Companies Struggle with Compassionate Use Requests
Source: Pharmaceutical Technology,
Click here