Recent advances and further challenges in lyophilization.

While entering a new century, lyophilization in the pharmaceutical field has been subjected to ongoing development and steady expansion. This review aims to highlight recent advances but also to discuss further challenges in lyophilization. At first, the expanded range of pharmaceutical applications based on lyophilization is summarized. Moreover, novel formulation aspects and novel container systems are discussed, and the importance of the freezing step is outlined. Furthermore, the dogma of "never lyophilize above the glass transition temperature" is argued, and recent insights into novel stabilization concepts are provided. Process analytical technology (PAT) and quality by design (QbD) are now leading issues, and the design of the lyophilization equipment also might have to be reconsidered in the future.