Concepts and Strategies in the Design of Formulations for Freeze Drying

Abstract

In order to enhance the storage stability of water labile molecules the common practice is to employ lyophilization (freeze drying) process to create dry glassy state dosage form. The lyophilization process is not free of imparting stresses during the processing, and since what is in the formulation dictates the design of the processing conditions, both the formulation and process should be designed in such a way that the drug entity, especially protein molecule, behaves well against the stresses during the various steps or phases of freeze drying, namely, in-process stability, long-term storage stability, and sufficient stability post-reconstitution until it is administered into the patient body. Understanding of key attributes/liabilities of the protein molecules and the selection of excipients and design of process parameters is key to robust formulation and lyophilization process that can produce a product that has adequate stability, quality, and commercial manufacturing viability. The objective of this chapter is to discuss briefly the concepts and strategies that would help to design a robust formulation and a lyophilization process.