Comparison of ice fog methods and monitoring of controlled nucleation success after freeze-drying

Publication date: 10 March 2019Source: International Journal of Pharmaceutics, Volume 558Author(s): Ilona Vollrath, Wolfgang Friess, Angelika Freitag, Andrea Hawe, Gerhard WinterAbstractImproving freeze-drying processes regarding drying time and batch homogeneity is subject of ongoing research work. In this context, controlled nucleation raised great expectations. However, practically we face some challenges, e.g. how to non-destructively monitor successfully performed controlled nucleation. The question if different controlled nucleation methods lead to comparable products, as not every method can easily be implemented in lab and production scale equipment, is also of high interest. Additionally, the optimal nucleation temperature for controlled nucleation is an open question. In our study, we addressed these challenges. We successfully evaluated frequency modulated spectroscopy as a fast and non-destructive method to monitor controlled nucleation success and batch homogeneity. We found that the better homogeneity generated by controlled nucleation during the freezing step did not sustain in the dried product. Lyophilizates produced by three different ice fog methods for controlled nucleation were characterized by comparable specific surface areas but differed in residual moisture content. To investigate the impact of the ice nucleation temperature (TN) on the resulting specific surface area, we performed controlled nucleation at −3 °C and −10 °C. We concluded that...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research