Ybema H, Kolkman-Roodbeen L, te Booy M P, Vromans H
Technology Department, N.V. Organon, OSS, The Netherlands.
Pharm Res. 1995 Sep;12(9):1260-3. doi: 10.1023/a:1016248918285.
The aim of this study was to assess the rate limiting factors in the sublimation phase of freeze drying and to propose a simple model on the basis of these rate limitations.
A programmable freeze dryer was used. The load consisted of vials of varying size and various contents. To increase heat transfer, conductive paste was applied while the resistance toward mass transport was varied by using different restrictive capillaries.
It was found that heat transfer limits the rate of sublimation. Presence of the commonly used excipient mannitol did not have a consequence on the rate of sublimation. The same applied for the restrictions towards mass transport. It was found that there exists not only a barrier against heat transport under the vial, but also between the glass wall and the frozen solution.
From the results, a set of equations is proposed that enables to predict optimum sublimation conditions. For the pharmaceutical technologist this can serve as a simple and useful tool to derive a suitable freeze drying program.
本研究旨在评估冷冻干燥升华阶段的速率限制因素，并基于这些速率限制提出一个简单模型。
使用了一台可编程冷冻干燥机。负载由不同尺寸和各种内容物的小瓶组成。为了增加热传递，应用了导电糊剂，同时通过使用不同的限制性毛细管来改变对质量传递的阻力。
发现热传递限制了升华速率。常用辅料甘露醇的存在对升华速率没有影响。对质量传递的限制也是如此。发现不仅在小瓶下方存在热传递障碍，而且在玻璃壁和冷冻溶液之间也存在热传递障碍。
根据结果，提出了一组方程，能够预测最佳升华条件。对于制药技术人员来说，这可以作为推导合适的冷冻干燥程序的简单而有用的工具。
