Processing of thermosensitive biological API from suspension using an integrated continuous granulation – Drying – Milling line into powder ready for tableting

Abstract

Drying is broadly used to enhance the stability of thermosensitive biologics (for example proteins, probiotics) despite the risk of inadequate product quality after the drying process. Continuous fluidized bed drying is an attractive technology for these active pharmaceutical ingredients owing to the short mean residence time at elevated temperatures, compared to batch-type drying technologies and the possibility to closely monitor and precisely control the process. In this work, an integrated continuous granulation – drying – milling line was used to manufacture granules ready for tableting from a suspension of probiotic bacteria. A mechanistic drying model suitable to predict the product temperature in the dryer and the moisture content of the granules was built. This allowed finding the optimal operating conditions for maximal bacteria load and low residual moisture content in the product, which has the potential to enable direct integration with the tableting unit. A continuous experiment was carried out with the in silico - optimized process parameters. The produced granules had high probiotic content and were suitable for tableting, which demonstrates the usefulness of the model-based process optimization in complex integrated pharmaceutical manufacturing processes.

Additional information

Funding

This work was supported by OTKA grants FK-132133, FK-138475 and the ÚNKP-21-4-I and ÚNKP-21-4-II New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund.