Temperature Measurement by Sublimation Rate as a Process Analytical Technology Tool in Lyophilization.

Product temperature (T) and drying time constitute critical material attributes and process parameters in the lyophilization process and especially during the primary drying stage. In the study, we performed a temperature measurement by the sublimation rate (TMbySR) to monitor the T value and determine the end point of primary drying. First, the water vapor transfer resistance coefficient through the main pipe from the chamber to the condenser (C) was estimated via the water sublimation test.

Optimization of primary drying condition for pharmaceutical lyophilization using a novel simulation program with a predictive model for dry layer resistance.

The purpose of this study was to develop a novel simulation program to accurately predict the maximum product temperature and the primary drying time in lyophilization using the predictive model for dry layer resistance, which is the resistance of dried cake against water vapor flow. Ten percent sucrose aqueous solution was selected as a model formulation. It was demonstrated that the deviations between the predicted and measured maximum product temperature were attributed to the error of dry layer resistance at a given drying condition, which was different from the measured dry layer resistance in a preliminary lyophilization run for the simulation program.

Determination for dry layer resistance of sucrose under various primary drying conditions using a novel simulation program for designing pharmaceutical lyophilization cycle.

Dry layer resistance, which is the resistance of dried cake against water vapor flow generated from sublimation, is one of the important parameters to predict maximum product temperature and drying time during primary drying in lyophilization. The purpose of this study was to develop the predictive model of dry layer resistance under various primary drying conditions using the dry layer resistance obtained from a preliminary lyophilization run. When the maximum dry layer resistance was modified under the assumption that the chamber pressure is zero, the modified dry layer resistance, which is defined as specific dry layer resistance, correlated well with the sublimation rate.