Pfizer Global Supply, Global Technology Services, 1776 Centennial Dr., McPherson, Kansas, USA.
Jogue Inc, 4142 Pacific Privado, Ontario, California, 91761, USA.
AAPS PharmSciTech. 2017 Oct;18(7):2808-2813. doi: 10.1208/s12249-017-0768-3. Epub 2017 Apr 5.
Secondary drying is the final step of lyophilization before stoppering, during which water is desorbed from the product to yield the final moisture content. We studied how chamber pressure and partial pressure of water vapor during this step affected the time course of water content of aqueous solutions of polyvinylpyrrolidone (PVP) in glass vials. The total chamber pressure had no effect when the partial pressure of water vapor was very low. However, when the vapor phase contained a substantial fraction of water vapor, the PVP moisture content was much higher. We carried out dynamic vapor sorption experiments (DVS) to demonstrate that the higher PVP moisture content was a straightforward result of the higher water vapor content in the lyophilizer. The results highlight that the partial pressure of water vapor is extremely important during secondary drying in lyophilization, and that lower chamber pressure set points for secondary drying may sometimes be justified as a strategy for ensuring low partial pressure of water vapor, especially for lyophilizers that do not inject dry gas to control pressure. These findings have direct application for process transfers/scale ups from freeze-dryers that do not inject dry gas for pressure control to those that do, and vice versa.
二次干燥是装塞前冻干的最后一步，在此过程中，产品中的水分被解吸，以达到最终的水分含量。我们研究了在此步骤中腔室压力和水蒸气分压如何影响玻璃小瓶中聚乙烯吡咯烷酮（PVP）水溶液的含水量随时间的变化。当水蒸气分压非常低时，总腔室压力没有影响。然而，当气相中含有相当一部分水蒸气时，PVP 的水分含量要高得多。我们进行了动态蒸汽吸附实验（DVS），以证明 PVP 较高的水分含量是冻干机中水蒸气含量较高的直接结果。结果表明，在冻干的二次干燥过程中，水蒸气分压极其重要，并且将二次干燥的腔室压力设定点设置得更低可能有时是合理的，因为这是一种确保低水蒸气分压的策略，特别是对于不注入干燥气体来控制压力的冻干机。这些发现对于从不注入干燥气体来控制压力的冻干机到那些注入干燥气体的冻干机，以及反之亦然的工艺转移/放大具有直接应用。
