Alternatives to Vial Lyophilization

Abstract

Lyophilization, alternately called freeze-drying, is widely practiced in the pharmaceutical industry for stabilizing sterile injectable drug products. Removal of water using this process protects the active drug from hydrolytic damage and other modes of degradation over shelf life. However, there is significant cost associated with it, due to the need for expensive capital equipment and infrastructure, large energy consumption, and overall labor-intensive nature of the operation. These obvious issues are driving the development of alternatives to lyophilization. These include sterile spray-drying, aseptic crystallization followed by sterile powder filling, vacuum-drying, drying on a fiber matrix, development of liquid products stabilized by optimal conditions, or by encapsulation of the active drug in a lipid matrix. This chapter examines the current state of the art, looks into advantages and disadvantages, and offers clues as to which alternatives may be better suited for a given need. Most of these generate flowable powders, so we have included information on aseptic powder filling into vials as well as innovative reconstitution-injection technology under development. Finally, we offer some insight into reformulation as a liquid.