ABSTRACT
INTRODUCTION Freeze-drying, or lyophilization, is a critical unit operation in pharmaceutical development and manufacturing because it allows removal of water from heat sensitive materials at low temperature, thereby avoiding thermal damage caused by more traditional drying operations. Freeze-drying is most important in production of injectable pharmaceuticals, but also finds application in manufacture of diagnostics and in certain solid oral dosage forms where rapid disintegration and dissolution is critical. In addition to allowing removal of water at low temperature, freeze-drying under appropriate conditions generally results in a solid material with a relatively high specific surface area, which facilitates rapid, complete dissolution. This is a critical quality attribute for drugs administered in emergency situations. Finally, freezedrying is more compatible with sterile operations than filling a solid powder into vials. The solution can be sterile filtered immediately before filling, and fill weights of liquids dispensed into the primary container can be more consistently controlled than filling of dry powders. Filling of a solution into vials also avoids potential problems with cross-contamination through airborne particulate matter, as well as exposure of workers to potentially hazardous drugs.
