Comparison of two DSC-based methods to predict drug-polymer solubility

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Predicting drug-polymer solubility is crucial for amorphous solid dispersion formulation.
• Differential scanning calorimetry (DSC) offers two primary methods: melting point depression and recrystallization.
• Selecting the appropriate DSC method requires understanding drug-polymer physicochemical properties.

Purpose of the Study:

• To compare the melting point depression and recrystallization methods for predicting drug-polymer solubility.
• To establish a guideline for selecting the most suitable DSC-based method.
• To investigate the influence of drug and polymer properties on method applicability.

Main Methods:

• Utilized DSC to determine solubilities of celecoxib, indomethacin, carbamazepine, and ritonavir in polyvinylpyrrolidone, hydroxypropyl methylcellulose, and Soluplus®.
• Applied the melting point depression method, requiring a distinct drug melting point.
• Employed the recrystallization method, necessitating a differentiable glass transition temperature (Tg) dependence on composition.

Main Results:

• The melting point depression method requires a well-defined drug melting point.
• Solubility measurements were achievable below the polymer's glass transition temperature (Tg) for some systems, especially with low Tg polymers.
• The recrystallization method is viable when the Tg shows distinct changes across specific drug composition ranges (50-90% w/w).

Conclusions:

• A decision-tree guideline is proposed for selecting between DSC-based melting point depression and recrystallization methods.
• Method selection depends on the physicochemical characteristics of the drug (e.g., melting point) and polymer (e.g., Tg, composition-Tg relationship).
• This work provides practical guidance for optimizing solubility predictions in drug formulation development.