Quality by Design Process Development Tools for Freeze Drying Co-solvent Pharmaceutical Formulations

Physical Sciences Inc. (PSI) has been awarded a grant from the National Institutes of Health to develop hardware and software tools that will support Quality by Design based development of freeze drying processes for co-solvent product formulations.

Co-solvent systems (water plus a single organic solvent) are used in freeze drying, particularly when the drug degrades in pure water during upstream processing such as compounding, aseptic filling, loading and freezing (e.g., bendamustine, alprostadil, and many peptide drugs). Degradation may also occur when the drug formulation is not sufficiently soluble in pure water (e.g., processing of self-assembled nanocarriers with drug). Unfortunately there are very few tools that aid process engineers in developing lyophilization cycles for these co-solvent formulations. PSI, in collaboration with the University of Connecticut School of Pharmacy, is developing a Tunable Diode Laser Absorption Spectroscopy based co-solvent mass flow rate monitor and a steady state heat and mass transfer model of vial-based freeze drying to enable efficient development and verification of co-solvent freeze drying cycles based on product temperature requirements.

This effort supports the U.S. FDA Process Analytical Technology and Regulatory Science initiatives by developing tools that can be directly used to infer information that affects product quality during processing and the product temperature. The combined use of the sensor and mathematical model will allow end users to predict and verify freeze drying cycle performance. This will result in products that support the development of efficient co-solvent product formulation freeze drying cycles. It targets some of the novel, emerging drug products. The development of robust and efficient cycles will reduce processing costs, result in lower drug costs and support a reduction in shortages of novel lyophilized drug therapies.

For more information, contact:

Mr. William Kessler
Vice President, Applied Optics
kessler@psicorp.com
Physical Sciences Inc.
Telephone: (978) 689-0003