Effect of composition dependence in Flory-Huggins parameters on solid dispersion stability prediction

Area of Science:

• Polymer Science and Engineering
• Materials Science
• Pharmaceutical Sciences

Background:

• Flory-Huggins theory is fundamental for phase diagram construction and stability analysis in polymer-solute systems.
• Pharmaceutical solid dispersions rely on phase diagrams for formulation design and stability assessment.
• Current models often use a temperature-dependent interaction parameter (χ(T)), but evidence suggests composition dependence (χ(ϕ,T)) is also important.

Purpose of the Study:

• To develop and analyze a novel Flory-Huggins mathematical framework incorporating composition-dependent interactions (χ(ϕ,T)).
• To quantify the impact of using χ(ϕ,T) versus χ(T) on predicting and interpreting phase behavior in solid dispersions.
• To investigate the implications for formulation stability and microstructural evolution.

Main Methods:

• Derived chemical potentials and stability conditions for binodal and spinodal calculations with χ(ϕ,T).
• Established generalized criteria for upper critical solution temperature (UCST) and lower critical solution temperature (LCST) behavior.
• Constructed and compared phase diagrams for three solid dispersion systems using both χ(T) and χ(ϕ,T) models.
• Developed a partial differential equation model to simulate microstructural spatiotemporal evolution.

Main Results:

• The composition-dependent model (χ(ϕ,T)) predicts substantial quantitative and qualitative differences in phase behavior compared to the temperature-dependent model (χ(T)).
• Generalized criteria for UCST and LCST were derived, enhancing phase behavior prediction.
• Simulations revealed rich demixing morphologies, including bicontinuous networks and droplet formation, validating the predicted stability landscapes.

Conclusions:

• Accounting for composition dependence in the Flory-Huggins interaction parameter (χ(ϕ,T)) is crucial for accurate phase behavior prediction in polymer-solute systems.
• The novel framework provides a more robust approach to formulation design and stability assessment for pharmaceutical solid dispersions.
• The findings highlight the importance of considering complex interactions for understanding and controlling microstructural evolution.