Drug-polymer-water interaction and its implication for the dissolution performance of amorphous solid dispersions

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• Amorphous solid dispersions (ASDs) are crucial for improving drug solubility and bioavailability.
• Predicting the in vitro and in vivo performance of ASDs remains a significant challenge in pharmaceutical development.

Purpose of the Study:

• To investigate the in vitro dissolution mechanisms of various ASD systems.
• To identify key physicochemical properties governing ASD performance and their correlation with dissolution.
• To evaluate the predictive potential of these properties for ASD performance.

Main Methods:

• Comprehensive characterization of ASDs including griseofulvin, felodipine, and ketoconazole with PVP-VA or HPMC-AS.
• Assessment of drug crystallization tendency, drug-polymer interactions, supersaturation, and polymer dissolution kinetics.
• Correlation of physicochemical properties with in vitro dissolution performance at various drug loadings and ratios.

Main Results:

• Ketoconazole/HPMC-AS ASD demonstrated superior dissolution performance attributed to low drug crystallization tendency, strong drug-polymer interaction, and effective supersaturation maintenance.
• HPMC-AS based ASDs generally outperformed PVP-VA counterparts, irrespective of drug loading or dose.
• Quantification of supersaturation and dissolution performance parameters were introduced as potential predictors for in vitro dissolution.

Conclusions:

• Drug-polymer interactions, crystallization tendency, and polymer properties significantly influence ASD dissolution.
• HPMC-AS shows promise for developing high-performance ASDs due to its favorable interactions and ability to maintain drug supersaturation.
• For fast-crystallizing drugs lacking strong polymer interaction, reducing dose and drug loading may be the only viable strategy to enhance dissolution.