In-Line Prediction of Secondary Drying Time from Measured Ice Nucleation Temperature During Lyophilization process:(TJPS-2020-0233.R2)

Abstract

Purpose. To propose an approach to find optimal secondary drying time (t^SD) specifically for each lyophilized batch by predicting residual moisture at the beginning of secondary drying (C_s⁰) using measured ice nucleation temperatures (T_N) obtained in-line. 
Methods. Value of C_s⁰ was determined by minimizing the residual error between measured (T_P^SD,mea) and calculated (T_P^SD,cal) product temperatures during secondary drying. Value of T_N was determined by using product temperatures during freezing (T_P^Fr). Then, the correlation between C_s⁰ and T_N was conducted and resulted in the C_s⁰prediction equation. This equation was used with developed mathematical simulation to propose t^SD prediction model for each lyophilized batch. 
Results. C_s⁰ and T_N of training lyophilized batches were successfully determined by using T_P^SD and T_P^Fr, respectively. Linear relationship was assumed and used to predict C_s⁰ from T_N of testing lyophilized batch. The accuracy of t^SD prediction model was confirmed by comparing calculated and measured final product residual moisture (C_s^t) of testing lyophilized batch. Then, the optimum t^SD for each targeted C_s^t was predicted from given range of T_N. 
Conclusion. Measured T_N could be used to predict the optimum t^SD for each lyophilization batch. Nevertheless, further study is required before applying this approach in pharmaceutical industry scale.