COSMOPharm

COSMOPharm applies the quantum mechanics-aided COSMO-SAC activity coefficient model to predict the thermodynamic compatibility of drugs and polymers in amorphous solid dispersions for rational selection of polymeric carriers that enhance drug bioavailability.

Key Features:

• COSMO-SAC Integration: Utilizes the COSMO-SAC activity coefficient model based on quantum-mechanically derived sigma-profiles of molecular species without parameter fitting to experimental data.
• Solubility Prediction: Calculates drug-polymer solubility using standard thermodynamic equilibrium relations based on COSMO-SAC predicted activity coefficients.
• Miscibility Assessment: Evaluates drug-polymer miscibility to estimate amorphous-amorphous phase separation behavior.
• Polymer Sigma-Profile Generation: Derives polymer sigma-profiles from shorter oligomers by replicating properties of their central monomer unit(s).
• Quantitative Accuracy: Achieves an overall average absolute deviation of 13% in weight fraction drug solubility predictions compared to experimental data.
• Qualitative Categorization: Correctly categorizes different polymer types in terms of their compatibility with drugs.
• Sensitivity Analysis: Analyzes the sensitivity of COSMO-SAC results to different model configurations and sigma-profiles of polymers.

Scientific Applications:

• Polymer Screening: Screens polymeric carriers for pharmaceutical amorphous solid dispersions based on predicted thermodynamic compatibility.
• Formulation Design: Assists in the design of pharmaceutical formulations by predicting API-polymer thermodynamic compatibility.
• Phase Separation Prediction: Provides meaningful estimations of amorphous-amorphous phase separation in drug-polymer systems.
• Compatibility Ranking: Ranks and categorizes polymers by their compatibility with specific drug compounds.

Methodology:

COSMOPharm calculates drug-polymer solubility and miscibility using standard thermodynamic equilibrium relations based on activity coefficients predicted by COSMO-SAC, relying on quantum-mechanically derived sigma-profiles of the considered molecular species with polymer sigma-profiles determined from their shorter oligomers by replicating properties of central monomer unit(s).