Interplay of Drug-Polymer Interactions and Release Performance for HPMCAS-Based Amorphous Solid Dispersions

Area of Science:

• Pharmaceutical Sciences
• Polymer Chemistry
• Drug Delivery

Background:

• Amorphous solid dispersions (ASDs) are crucial for enhancing drug solubility and bioavailability.
• The interaction between drug molecules and polymers within ASDs is complex and influences drug release kinetics.
• Understanding these drug-polymer interactions is vital for designing effective drug delivery systems.

Purpose of the Study:

• To investigate the impact of drug chemistry on drug release from hydroxypropyl methylcellulose acetate succinate (HPMCAS)-based ASDs.
• To explore the role of electrostatic interactions and complexation in modulating drug release.
• To establish relationships between drug-polymer complex formation and release performance.

Main Methods:

• Utilized surface area normalized dissolution to assess drug release rates.
• Employed coprecipitation experiments to quantify the tendency of drugs to form insoluble complexes with HPMCAS.
• Investigated the influence of pH and drug ionization on complex formation and release.

Main Results:

• Drug release from HPMCAS-based ASDs was categorized based on the extent of insoluble complex formation.
• Neutral or anionic drugs showed adequate release at pH 6.8, even at higher concentrations.
• Cationic drugs formed insoluble complexes with HPMCAS, leading to poor drug release from ASDs.
• A weakly basic drug exhibited reduced release in its ionized state within an ASD, contrary to its behavior as a neat amorphous drug.

Conclusions:

• Electrostatic interactions between HPMCAS and lipophilic cationic drugs promote insoluble complex formation.
• This complexation significantly impairs the release performance of ASDs containing such drugs.
• Tailoring drug-polymer interactions is essential for optimizing drug release from ASDs.