Thermal stability of mefruside-polyvinylpyrrolidone solid dispersions

Area of Science:

• Pharmaceutical Technology
• Materials Science
• Drug Delivery Systems

Background:

• Solid dispersions are crucial for enhancing drug solubility and bioavailability.
• Mefruside, a diuretic, can exhibit poor solubility, necessitating formulation strategies like solid dispersions.
• Polyvinylpyrrolidone (PVP) is a common polymer used in solid dispersion formulations due to its favorable properties.

Purpose of the Study:

• To evaluate the physical stability of mefruside-polyvinylpyrrolidone (PVP) 30 solid dispersions.
• To determine the optimal ratio of mefruside to PVP 30 for enhanced drug stability.
• To investigate the impact of mechanical and thermal stress on mefruside recrystallization within solid dispersions.

Main Methods:

• Preparation of mefruside-PVP 30 solid dispersions at varying ratios (9/1, 7/3, 5/5 g/g).
• Application of mechanical stress through tableting.
• Application of allothermic stress by exposing dispersions to temperatures of 50, 60, and 70°C for up to 240 hours.
• Assessment of mefruside recrystallization and crystallinity changes using analytical techniques.

Main Results:

• The mefruside/PVP 30 solid dispersion at a 5/5 (g/g) ratio exhibited no recrystallization of mefruside after stress testing.
• A slight increase in mefruside crystallinity was observed in the 7/3 (g/g) solid dispersion.
• A significant increase in mefruside crystallinity was detected in the 9/1 (g/g) solid dispersion, indicating instability.

Conclusions:

• The 5/5 (g/g) mefruside-PVP 30 solid dispersion demonstrates superior physical stability compared to higher mefruside content formulations.
• Formulation ratio is a critical factor influencing the recrystallization behavior of mefruside in PVP solid dispersions.
• Understanding drug recrystallization mechanisms in high-energy solid dispersion products is essential for developing stable pharmaceutical formulations.