Purpose: To propose an approach to find optimal secondary drying time (tSD) specifically for each lyophilized batch by predicting residual moisture at the beginning of secondary drying (Cs0) using measured ice nucleation temperatures (TN) obtained in-line. Materials and Methods: Value of Cs0 was determined by minimizing the residual error between measured (Tp SD,mea) and calculated (Tp SD,cal) product temperatures during secondary drying. Value of TN was determined by using product temperatures during freezing (TP Fr). Then, the correlation between Cs0 and TN was conducted and resulted in the Cs0 prediction equation. This equation was used with developed mathematical simulation to propose tSD prediction model for each lyophilized batch. Results: Cs0 and TN of training lyophilized batches were successfully determined by using Tp SD and TP Fr, respectively. Linear relationship was assumed and used to predict Cs0 and TN of testing lyophilized batch. The accuracy of tSD prediction model was confirmed by comparing calculated and measured final product residual moisture (Cst) of testing lyophilized batch. Then, the optimum tSD for each targeted Cst was predicted from given range of TN. Conclusion: Measured TN could be used to predict the optimum tSD for each lyophilization batch. Nevertheless, further study is required before applying this approach in pharmaceutical industry scale.
Faculty of Pharmaceutical Sciences, Chulalongkorn University
Supakatisant, Tharavich; Sutanthavibul, Narueporn; and Kittithreerapronchai, Oran
"In-line prediction of secondary drying
time from measured ice nucleation temperature during lyophilization process,"
The Thai Journal of Pharmaceutical Sciences: Vol. 45:
5, Article 5.
Available at: https://digital.car.chula.ac.th/tjps/vol45/iss5/5