Spray-Drying Process Optimization and Modeling for an Inhaled Dry Powder of 5-Azacytidine for Treating Local and...

Area of Science:

• Pharmaceutical Sciences
• Chemical Engineering
• Materials Science

Background:

• A spray-dried formulation of 5-azacytidine (5-AZA) showed promise for metastatic lung cancer treatment.
• Clinical applications require doubling the active drug loading in the formulation.

Purpose of the Study:

• To increase 5-AZA loading in spray-dried powders.
• To identify process parameters controlling powder properties.
• To investigate the spray drying of l-leucine and trehalose using DMSO and water.

Main Methods:

• Spray drying of 5-AZA formulations using in-line mixing of DMSO and aqueous solutions.
• Variation of process parameters to control powder properties.
• Application of Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) for modeling droplet drying.

Main Results:

• Successful manufacture of powders with high yields and a core-shell structure.
• Achieved high 5-AZA loading with controlled residual DMSO.
• Demonstrated the manufacturability of low glass transition temperature (Tg) materials via spray drying.

Conclusions:

• This study enables the production of dry inhalable 5-AZA powder for lung cancer treatment.
• It expands the capabilities of spray drying for previously unmanufacturable low Tg materials.
• Aligning experimental data with theoretical models enhances understanding of complex spray drying processes.