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
Which of the following business challenge poses the greatest threat to your company?
Building a sustainable pipeline of products
Attracting a skilled workforce
Obtaining/maintaining adequate financing
Regulatory compliance
Building a sustainable pipeline of products
20%
Attracting a skilled workforce
28%
Obtaining/maintaining adequate financing
12%
Regulatory compliance
40%
View Results
Eric Langer Outsourcing Outlook Eric LangerBiopharma Outsourcing Activities Update
Cynthia Challener, PhD Ingredients Insider Cynthia Challener, PhDAppropriate Process Design Critical for Commercial Manufacture of Highly Potent APIs
Jill Wechsler Regulatory Watch Jill Wechsler FDA and Manufacturers Seek a More Secure Drug Supply Chain
Sean Milmo European Regulatory WatcchSean MilmoQuality by Design?Bridging the Gap between Concept and Implementation
Medicare Payment Data Raises Questions About Drug Costs
FDA Wants You!
A New Strategy to Tackle Antibiotic Resistance
Drug-Diagnostic Development Stymied by Payer Concerns
Obama Administration Halts Attack on Medicare Drug Plans
Source: Pharmaceutical Technology,
Click here