Comparative evaluation of ternary amorphous solid dispersions: Identifying optimal excipient systems for enhancing...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery
• Materials Science

Background:

• Poor aqueous solubility of Active Pharmaceutical Ingredients (APIs) limits oral bioavailability and therapeutic efficacy.
• Amorphous Solid Dispersions (ASDs) are a key strategy to overcome API solubility challenges.
• Ternary ASDs, incorporating a third component, offer enhanced formulation flexibility and performance.

Purpose of the Study:

• To systematically review formulation strategies for ternary ASDs.
• To analyze comparative outcomes and molecular mechanisms of ternary ASDs.
• To evaluate ternary ASDs in improving solubility, dissolution, stability, and pharmacokinetics.

Main Methods:

• Comprehensive literature search (2015-2025) in Scopus, PubMed, Web of Science.
• Focus on experimental studies evaluating ternary ASDs (Drug:Polymer:Polymer, Drug:Polymer:Surfactant, etc.).
• Selection based on solubility enhancement, dissolution, in vitro-in vivo correlation, and mechanistic insights.

Main Results:

• Ternary ASDs outperform binary systems, with surfactant-based systems showing highest solubility enhancement (up to 810.81-fold).
• Polymer-polymer and polymer-excipient systems also improved dissolution and pharmacokinetic parameters.
• Mechanisms include micellization, hydrogen bonding, molecular dispersion, and recrystallization inhibition.

Conclusions:

• Ternary ASD systems are a significant advancement for formulating poorly soluble drugs.
• They effectively modulate solubility, dissolution, and pharmacological outcomes via molecular interactions.
• Future research should focus on component selection and predictive modeling for ternary ASDs.