Development of a small-scale spray-drying approach for amorphous solid dispersions (ASDs) screening in early drug...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Standard methods for screening amorphous solid dispersions (ASDs) have limitations in predicting drug-polymer miscibility.
• Accurate prediction of miscibility is crucial for selecting appropriate carriers and drug-loading (DL) in spray-dried solid dispersions (SDSDs).

Purpose of the Study:

• To develop and optimize a small-scale spray-drying technique for routine screening of ASDs.
• To enhance the prediction accuracy of drug-polymer miscibility in SDSDs compared to conventional methods.

Main Methods:

• A Design of Experiments (DoE) approach was used to optimize spray-drying parameters (inlet temperature, pump speed, airflow) for 100 mg batches of Itraconazole/HPMCAS-LF and Itraconazole/Soluplus.
• Optimized conditions were validated with different drugs and polymers, adapted for small cyclone use, and downscaled to 20 mg batches.
• Drug-polymer miscibility was assessed using modulated differential scanning calorimetry (mDSC).

Main Results:

• Optimized spray-drying parameters successfully maximized yield for both 100 mg and 20 mg ASD batches.
• Yields ranged from 10.1% to 40.6% for 20 mg batches and 51.1% to 81.0% for 100 mg batches.
• The spray-drying method proved effective for characterizing drug-polymer miscibility.

Conclusions:

• Small-scale spray-drying is a viable and effective screening approach for amorphous solid dispersions.
• Integrating spray-drying into early screening phases offers greater prediction accuracy for SDSD miscibility and performance.
• This method overcomes limitations of traditional screening techniques, facilitating better carrier and drug-loading selection.