Effect of the drug-excipient ratio in matrix-type-controlled release systems: computer simulation study

Area of Science:

• Pharmaceutical Sciences
• Computational Chemistry
• Materials Science

Background:

• Inert matrix systems are widely used for controlled drug delivery.
• Understanding drug release mechanisms and percolation phenomena is vital for optimizing dosage forms.
• Current methods for evaluating drug percolation thresholds have limitations.

Purpose of the Study:

• To investigate drug release kinetics from inert matrix systems using computer simulations.
• To develop and validate a new statistical method for determining the drug percolation threshold.
• To explore the relationship between initial drug load, trapped drug, and percolation thresholds.

Main Methods:

• Computer simulation of a simple cubic lattice representing the matrix system.
• Random occupation of lattice sites with drug and excipient at varying ratios.
• Simulation of a diffusive process to model drug release.
• Fitting release profiles to the square root of time and power law models.
• Nonlinear regression analysis to determine percolation thresholds.

Main Results:

• Drug release profiles were accurately described by different models depending on proximity to percolation thresholds.
• A relationship between initial drug load and the amount of trapped drug was identified and modeled by an error function.
• Percolation thresholds were successfully determined and found to be dependent on the exposed surface area.
• Simulated percolation thresholds aligned with theoretical predictions.

Conclusions:

• Computer simulations provide a powerful tool for studying drug release from inert matrices.
• The proposed statistical method effectively evaluates drug percolation thresholds.
• Drug release behavior and percolation phenomena are influenced by drug load and system geometry.
• This work offers insights into optimizing the design of drug delivery systems based on percolation theory.