Screening methodologies for the development of spray-dried amorphous solid dispersions.

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Computational Chemistry

Background:

• Amorphous solid dispersions (ASDs) are crucial for enhancing the solubility and bioavailability of poorly soluble drugs.
• Early-stage development of ASDs often involves extensive screening of drug-polymer systems and processing parameters.
• Spray drying is a common technique for producing ASDs, but requires careful optimization.

Purpose of the Study:

• To introduce a novel screening methodology for the early development of spray-dried amorphous solid dispersions (ASDs).
• To enable efficient assessment of drug-polymer miscibility and amorphous stability.
• To guide the selection of optimal drug loading ranges for experimental validation.

Main Methods:

• A predictive model integrating thermodynamic, kinetic, and manufacturing factors was developed to estimate miscibility and phase behavior.
• A small-scale solvent casting protocol was established for rapid evaluation of amorphous stability.
• Lab-scale spray drying was employed to produce ASDs for powder characterization and comparison with model predictions.

Main Results:

• The computational model successfully ranked polymers based on miscibility, aligning with experimental solvent casting and spray drying results.
• The model's predicted optimal drug loading range was consistent with experimental findings.
• The integrated methodology demonstrated high predictability for ASD formulation development.

Conclusions:

• The presented screening methodology allows for in silico assessment of amorphous formulation candidates, identifying suitable polymers and optimal drug loads.
• Solvent casting experiments provide further refinement using minimal active pharmaceutical ingredient (API).
• This approach streamlines the selection of promising formulations for subsequent spray drying experiments.