Optimization of nucleation and crystallization for lyophilization using gap freezing

摘要

This application discloses devices, articles, and methods useful for producing lyophilized cakes of solutes. The devices and articles provide for a method of freezing liquid solutions of the solute by the top and the bottom of the solution simultaneously and at approximately the same rate. The as frozen solution can then provide a lyophilized cake of the solutes with large and uniform pores.

主权项

1. A method comprising:
providing a lyophilization chamber comprising a heat sink surface in thermal communication with a refrigerant; loading a container comprising a liquid solution into the lyophilization chamber, the liquid solution comprising a solute and a solvent and characterized by a top surface and a bottom surface; forming a thermal insulator between the container and the heat sink surface; lowering the temperature of the heat sink and thereby the ambient temperature in the lyophilization chamber comprising the container to a temperature sufficient to freeze the liquid solution,the thermal insulator selected to provide freezing of the liquid solution from the top and the bottom surfaces at approximately the same temperature and thereby form a frozen solution; andreducing the ambient pressure in the chamber to lyophilize the frozen solution.