COSMOPharm: Drug-Polymer Compatibility of Pharmaceutical Amorphous Solid Dispersions from COSMO-SAC

Area of Science:

• Computational chemistry
• Materials science
• Pharmaceutical sciences

Background:

• Drug-polymer compatibility is crucial for amorphous solid dispersions (ASD) to improve drug bioavailability.
• Rational selection of polymeric carriers requires accurate prediction of drug-polymer interactions.

Purpose of the Study:

• To apply and examine the quantum mechanics-aided COSMO-SAC model for predicting thermodynamic compatibility between drugs and polymers.
• To evaluate drug solubility and miscibility using COSMO-SAC predictions for ASD formulation.

Main Methods:

• Utilized the COSMO-SAC activity coefficient model based on quantum-mechanically derived σ-profiles.
• Derived polymer σ-profiles from oligomers, replicating central monomer unit properties.
• Calculated drug-polymer compatibility via solubility and miscibility using thermodynamic equilibrium relations.

Main Results:

• Achieved an average absolute deviation of 13% in weight fraction drug solubility predictions.
• Qualitatively categorized polymer compatibility and estimated amorphous-amorphous phase separation.
• Identified oligomer structure's importance for polymer σ-profiles in predicting compatibility.

Conclusions:

• COSMO-SAC is an efficient, first-principles method for predicting drug-polymer compatibility and screening polymers for ASD.
• The model offers a favorable performance-cost ratio, relying solely on calculations.
• The open-source tool COSMOPharm facilitates further research and formulation design.