SUMMARY
It is important to view product and process development for freeze-dried parenterals as an integrated process rather than
as a collection of independent activities. When doing formulation and initial cycle development, the development scientist
must be aware of the type of equipment to which the product will be transferred in the next stage of development. The scientist
must also understand the capability of the equipment, and must take it into account as cycle conditions are developed. This
approach becomes particularly important for formulations that will withstand aggressive cycle conditions.
To generate a design space similar to the one in this discussion, it is necessary to have a thorough understanding of both
the characteristics of the formulation and the capability of equipment. This is the major intent of the Quality by Design
paradigm.
Steven L. Nail, PhD, is a senior Baxter research scientist at Baxter Pharmaceutical Solutions, Inc., Bloomington, IN, 812.355.7270, steven_nail@baxter.
Jim A. Searles, PhD, is director of development at Aktiv-Dry, LLC, Boulder, CO.
REFERENCES
1. Design space to facilitate qality initiative implementation. The Gold Sheet. 2005 Apr;39 (4).
2. Gieseler H, et al. Evaluation of tunable diode laser absorption spectroscopy for in-process water vapor mass flux measurements
during freeze drying. J Pharm Sci. 2007;96:1776–93.
3. Chang BS, Fischer NL. Development of an efficient single-step freeze-drying cycle for protein formulations. Pharm Res.
1995;12:831–7.
4. Nail SL. The effect of chamber pressure on heat transfer in the freeze-drying of parenteral solutions. J Parenteral Drug
Assoc. 1980;34:358–68.
5. Searles JA. Observation and implications of sonic water vapor flow during freeze-drying. Amer Pharm Rev. 2004;7 (2):58–69.
|
