Practical Formulation and Process Development of Freeze-Dried Products

Abstract

Freeze-drying science and technology continues to evolve and increase in importance because of the emergence of biotechnology drugs that are too unstable to be commercially available as ready-to-use solutions. As more new drug compounds need to be developed as freeze-dried products, this minireview article provides practical guidance and commentary on the latest literature articles on formulation and process development of freeze-dried products. This article contains a table that provides the quantitative formulations of all commercial freeze-dried protein pharmaceutical products through 2004.

Keywords:

• freeze-drying
• lyophilization
• formulation
• process development
• proteins
• parenterals
• stability
• freezing
• drying
• sublimation
• co-solvents
• lyoprotectants
• excipients

Notes

^a“Rate of freezing” can be easily misinterpreted. There is a difference between actual freezing rate and the rate of temperature ramping. The freezing process first involves cooling the solution prior to ice nucleation, then ice crystals begin to grow at a certain rate. Freezing rate is determined largely by the amount of supercooling prior to ice nucleation. The amount or rate of supercooling cannot be directly controlled.

^bSonic flow is the speed of sound, the maximum possible velocity of a gas flowing in a cylinder. Sonic choked flow occurs when downstream pressure is reduced and gas flow reaches sonic flow at the exit point. Any further reduction in downstream pressure will not affect gas flow and the system is said to be “choked.”