Experimental observations and dissipative particle dynamic simulations on microstructures of pH-sensitive polymer...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Computational Chemistry

Background:

• Amorphous solid dispersion (ASD) is crucial for improving the dissolution rates of poorly soluble drugs.
• The inherent instability and molecular mechanisms of kinetic stability in ASDs remain poorly understood.
• Understanding these factors is key to developing more effective drug delivery systems.

Purpose of the Study:

• To investigate the pH-dependent stability and dissolution behavior of lacidipine-Eudragit E 100 amorphous solid dispersions.
• To elucidate the microstructural differences influencing drug release at varying pH levels.
• To explore the utility of Dissipative Particle Dynamics (DPD) simulations in understanding ASD microstructure.

Main Methods:

• Preparation of lacidipine-Eudragit E 100 amorphous solid dispersions (20% drug loading) via solvent evaporation.
• In vitro dissolution testing across different pH media (1.2 and 6.8).
• Time-dependent measurements of supersaturation and particle size, coupled with Dissipative Particle Dynamics (DPD) simulations.

Main Results:

• The amorphous solid dispersion exhibited a significantly high dissolution rate, which was notably pH-dependent.
• Eudragit E 100 demonstrated differential inhibition of crystal growth at pH 1.2 versus pH 6.8.
• DPD simulations revealed distinct microstructures: swollen at pH 1.2 (rapid release) and compacted at pH 6.8 (slow dissolution).

Conclusions:

• The pH-dependent microstructure of amorphous solid dispersions significantly impacts drug release kinetics.
• Dissipative Particle Dynamics simulations offer valuable insights into the structural basis of ASD performance.
• This study provides a foundation for designing more kinetically stable amorphous solid dispersions.