Dynamic Pressure Rise in the Drying Chamber as a Remote Sensing Method for Monitoring the Temperature of the Product During the Primary Drying Stage of Freeze Drying

Abstract

A novel dynamic pressure rise method is developed as a remote sensing procedure for determining at different times during the primary drying stage of the freeze drying process (i) the temperature of the moving interface between the dried and frozen layers of the product, (ii) the temperature close to the upper surface of the dried layer of the product. (iii) the temperature of the bonom surface of the frozen layer of the product, and (iv) the temperature profile of the frozen layer of the product. Funhermore, by knowing the temperature ofthe heating plate and determiningthe value of the temperature of the moving interface from the dynamic pressure rise method, the value of the position of the moving interface could be determined by an expression presented in this work.

Advanced approach to build the design space for the primary drying of a pharmaceutical freeze‐drying process

“…13,[26][27][28] r One of the algorithms using the pressure rise curve obtained by isolating the drying chamber from the condenser (pressure rise test). [29][30][31][32][33][34] Product resistance to vapor flow can be determined using various methods:…”

“…• the TDLAS sensor, 24 • one of the algorithms using the pressure rise test, [29][30][31][32][33][34][35] • an equation involving product-specific surface area, 36 • the monitored product temperature profile, 37 • a special weighing device placed in the chamber to measure the sublimation flux (i.e., m) and product temperature in the weighed vials. [38][39][40] A detailed discussion and comparison of the methods available to determine model parameters is given in Ref.…”

In-Line Optimization and Control of an Industrial Freeze-Drying Process for Pharmaceuticals

“…Most of them use the pressure rise test (PRT) to monitor the process: the valve placed between the drying chamber and the condenser is periodically closed for a short time interval (typically 5-30 s), and the measured pressure rise is related to the temperature of the product by means of a mathematical model. Several algorithms were proposed to interpret the PRT, namely the Barometric Temperature Measurement, 17-20 the Manometric Temperature Measurement, [21][22][23][24] the Dynamic Pressure Rise, 25 the Pressure Rise Analysis, 26,27 and the Dynamic Parameters Estimation (DPE) 28,29 : the type and the details of the mathematical model, and the parameters that are estimated, are the main differences among the various algorithms.…”

Computer-Aided Framework for the Design of Freeze-Drying Cycles: Optimization of the Operating Conditions of the Primary Drying Stage

“…Various experimental methods were developed in the past to evaluate Kv and Rp, e.g., the test of pressure rise: the drying chamber is isolated from the condenser for a short time interval (usually ranging from 5-10 to 30 s) closing a valve in the duct connecting the chamber to the condenser and the pressure variation in the chamber, due to water vapor accumulation, is measured. Then, model parameters (Kv and Rp), as well as other variables like product temperature and the residual amount of ice, are estimated looking for the best fit between the values of chamber pressure measured and those calculated using a mathematical model of the process [22][23][24][25][26][27]. As an alternative to this method, it is possible to use Tunable Diode Laser Absorption Spectroscopy (TDLAS) to estimate Kv and Rp, beside product temperature and the residual amount of ice [28][29][30].…”