Highly efficient miniaturized coprecipitation screening (MiCoS) for amorphous solid dispersion formulation...

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• Poorly soluble compounds pose formulation challenges for traditional manufacturing methods like spray drying and melt extrusion.
• Amorphous solid dispersions are crucial for improving the bioavailability of such compounds.
• Microprecipitated bulk powder (MBP) offers a novel approach to creating amorphous formulations.

Purpose of the Study:

• To develop and validate an efficient high-throughput screening method for microprecipitated bulk powder (MBP) formulation development.
• To identify optimal formulation parameters including polymer type, drug loading, and solvent/antisolvent ratios.
• To demonstrate the utility of the method for both early and late-stage pharmaceutical development.

Main Methods:

• Development of miniaturized coprecipitation screening (MiCoS) using a 96-well platform.
• Integration of drug-polymer mixing, controlled precipitation, filtration, drying, and high-throughput characterization.
• Application of MiCoS to a model compound, glybenclamide, to determine optimal formulation parameters.

Main Results:

• The MiCoS method successfully generated amorphous microprecipitated bulk powder (MBP) formulations.
• Optimal conditions for glybenclamide MBP included hydroxypropylmethylcellulose acetate succinate, ≤40% drug loading, and an antisolvent (0.01 N HCl) to solvent (dimethylacetamide) ratio of ≥5:1.
• The selected formulations demonstrated favorable solid-state stability and kinetic solubility.

Conclusions:

• Miniaturized coprecipitation screening (MiCoS) is an effective high-throughput tool for developing amorphous microprecipitated bulk powder (MBP) formulations.
• This method facilitates rapid selection of optimal formulation parameters for poorly soluble drugs.
• MiCoS supports early-stage research (efficacy, PK, toxicology) and late-stage development (formulation optimization).