Characterization and stability of ternary solid dispersions with PVP and PHPMA

Area of Science:

• Pharmaceutical Science
• Materials Science
• Physical Chemistry

Background:

• Poorly soluble drugs often pose challenges in formulation due to poor bioavailability.
• Amorphous solid dispersions are a strategy to enhance solubility and dissolution rates.
• Immiscible binary solid dispersions can suffer from drug crystallization, limiting their effectiveness.

Purpose of the Study:

• To investigate the impact of incorporating a third polymer on the stability of amorphous solid dispersions.
• To evaluate the role of hydrogen bonding interactions in ternary solid dispersions.
• To determine the thermodynamic favorability of drug-polymer mixing in amorphous systems.

Main Methods:

• Preparation of ternary solid dispersions using spray drying with model drugs (griseofulvin, progesterone, phenindione), polyvinylpyrrolidone (PVP), and poly[2-hydroxypropyl methacrylate] (PHPMA).
• Assessment of the physical stability of amorphous solid dispersions over time.
• Calculation of the energy of mixing using Flory-Huggins theory based on melting point data.

Main Results:

• Binary solid dispersions (drug/PVP) showed rapid crystallization for griseofulvin and were not feasible for progesterone and phenindione.
• Incorporation of PHPMA into ternary solid dispersions (drug/PHPMA/PVP) significantly prolonged the amorphous state for all model drugs.
• Calculated free energy of mixing correlated well with observed stability, with griseofulvin exhibiting the lowest free energy.

Conclusions:

• The addition of a third polymer, PHPMA, to immiscible binary solid dispersions effectively stabilizes the amorphous form of poorly soluble drugs.
• Ternary solid dispersions offer a superior approach to binary systems for maintaining drug amorphicity.
• Thermodynamic favorability, as indicated by the energy of mixing, plays a crucial role in the stability of amorphous solid dispersions.