Atmospheric freeze drying for the reduction of powder electrostatics of amorphous, low density, high surface area pharmaceutical powders

Abstract

Amorphous itraconazole (ITZ) was prepared by Thin Film Freezing (TFF) utilizing 1,4-dioxane as the solvent with subsequent solvent removal via conventional tray lyophilization (ITZ LYO) or atmospheric freeze drying (ITZ AFD). ITZ AFD was prepared under various drying conditions to assess the influence of drying parameters on powder properties. XRD analysis confirmed all products were amorphous and DSC analysis revealed both drying processes resulted in the formation of the nematic mesophase of ITZ. SEM revealed a larger pore size and agglomerate size with fewer fine particles (i.e. less than 10 microns in diameter) for ITZ AFD compared to ITZ LYO. Residual solvent analysis revealed a primary drying temperature of −10°C resulted in residual solvent levels above the acceptable limits set by the International Conference on Harmonization as a result of microcollapse. Primary drying temperatures of less than −10°C resulted in acceptable residual solvent levels. The extent of microcollapse did not alter the macrostructure of the resulting powder. Powder flowability was determined to be similar for ITZ AFD and ITZ LYO based on Carr’s index and the Hausner ratio, as well as by dynamic angle of repose. All powders displayed poor flowability. Chargeability measurements demonstrated a lower charge transfer for ITZ AFD powders compared to ITZ LYO due to a combination of factors including differences in residual solvent level, particle size, pore size, surface area, and fine particles content. The reduction in chargeability as a result of AFD is highly desirable because it allows for improved powder handling and use post-production.

Keywords::

• Chargeability
• lyophilization
• atmospheric freeze drying
• high specific surface area
• electrostatic

Acknowledgements

The authors would like to acknowledge Enavail for assistance with contact angle measurements. Additionally the authors wish to acknowledge Dr. Hugh Smyth and Dr. Steven Marek for their assistance and discussion regarding the measurement of powder flow and chargeability.

Declarations of interest

The authors report no declarations of interest.