Use of manometric temperature measurement (MTM) and SMART™ freeze dryer technology for development of an optimized freeze-drying cycle
Use of manometric temperature measurement (MTM) and SMART™ freeze dryer technology for development of an optimized freeze-drying cycle
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DOI：
10.1002/jps.20982
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发表时间：
2007-12-01
影响因子：
3.8
通讯作者：
Pikal, Michael J.
中科院分区：
文献类型：
--
作者：
Gieseler, Henning;Kramer, Tony;Pikal, Michael J.
本报告首次提供了在9个月的测试期间使用SMART（TM）冷冻干燥机技术的实验总结。约300 cm 2的实验室冷冻干燥机，与室体积107.5 L的最小冰升华面积，发现与以前的实验中获得的数据与较小的冷冻干燥机（52 L）一致。发现使用不同类型的辅料、制剂和小瓶的循环设计具有良好的重现性。SMART（TM）初级干燥终点估计在大多数实验中是准确的，但是当产品在进行第一次MTM测量之前没有完全达到稳态条件时，显示出对初级循环时间的过度预测。5%蔗糖混合物在不同填充深度下的产品阻力数据是非常可重复的。由SMART（TM）测定的产品温度通常在约50%的初级干燥时间内与热电偶数据良好一致，如预期的那样，在初级干燥结束时出现显著偏差，但是对于高固体含量的制剂，（16.6% Pfizer产品）和聚乙烯吡咯烷酮（40 kDa）可能是由于在MTM试验期间无定形产品的水“再吸附”。(c)2007 Wiley-Liss，Inc.
This report provides, for the first time, a summary of experiments using SMART (TM) Freeze Dryer technology during a 9 month testing period. A minimum ice sublimation area of about 300 cm 2 for the laboratory freeze dryer, with a chamber volume 107.5 L, was found consistent with data obtained during previous experiments with a smaller freeze dryer (52 L). Good reproducibility was found for cycle design with different type of excipients, formulations, and vials used. SMART (TM) primary drying end point estimates were accurate in the majority of the experiments, but showed an over prediction of primary cycle time when the product did not fully achieve steady state conditions before the first MTM measurement was performed. Product resistance data for 5% sucrose mixtures at varying fill depths were very reproducible. Product temperature determined by SMART (TM) was typically in good agreement with thermocouple data through about 50% of primary drying time, with significant deviations occurring near the end of primary drying, as expected, but showing a bias much earlier in primary drying for high solid content formulations (16.6% Pfizer product) and polyvinylpyrrolidone (40 kDa) likely due to water "re-adsorption" by the amorphous product during the MTM test. (c) 2007 Wiley-Liss, Inc.