Evaluation of manometric temperature measurement, a process analytical technology tool for freeze-drying: Part I, product temperature measurement |
| |
Authors: | Xiaolin Tang Steven L. Nail Michael J. Pikal |
| |
Affiliation: | (1) Formulation Development, Centocor Inc, 145 King of Prussia Road, R-1-2, 19087 Radnor, PA;(2) Department of Industrial and Physical Pharmacy, Purdue University, 47907 West Lafayette, IN;(3) Lilly Research Laboratories, Eli Lilly & Co, 46285 Indianapolis, IN;(4) School of Pharmacy, U-2092, University of Connecticut, 372 Fairfield Road, 06269-2092 Storrs, CT |
| |
Abstract: | This study examines the factors that may cause systematic errors in the manometric temperature measurement (MTM) procedure used to evaluate product temperature during primary drying. MTM was conducted during primary drying using different vial loads, and the MTM product temperatures were compared with temperatures directly measured by thermocouples. To clarify the impact of freeze-drying load on MTM product temperatures, simulation of the MTM vapor pressure rise was performed, and the results were compared with the experimental results. The effect of product temperature heterogeneity in MTM product temperature determination was investigated by comparing the MTM product temperatures with directly measured thermocouple product temperatures in systems differing in temperature heterogeneity. Both the simulated and experimental results showed that at least 50 vials (5 mL) were needed to give sufficiently rapid pressure rise during the MTM data collection period (25 seconds) in the freeze dryer, to allow accurate determination of the product temperature. The product temperature is location dependent, with higher temperature for vials on the edge of the array and lower temperature for the vials in the center of the array. The product temperature heterogeneity is also dependent upon the freeze-drying conditions. In product temperature heterogeneous systems, MTM measures a temperature close to the coldest product temperature, even, if only a small fraction of the samples have the coldest product temperature. The MTM method is valid even at very low product temperature (−45°C). Published: February 10, 2006 |
| |
Keywords: | freeze-drying/lyophilization manometric temperature measurement process analytical technology for freeze drying product temperature heterogeneity |
本文献已被 PubMed SpringerLink 等数据库收录! |
|