Dissolution of irregularly-shaped drug particles: mathematical modelling

Area of Science:

• Pharmaceutical Sciences
• Physical Chemistry
• Chemical Engineering

Background:

• Accurate prediction of drug dissolution profiles is essential for understanding drug pharmacokinetics and dosage form bioavailability.
• Existing models often struggle to accurately represent the dissolution of irregularly shaped particles.

Purpose of the Study:

• To develop a novel mathematical model for predicting the dissolution of irregularly shaped particles.
• To investigate the influence of particle shape and surface curvature on drug dissolution rates.
• To incorporate recrystallization processes into the dissolution model.

Main Methods:

• Developed a complete dissolution model incorporating surface kinetics and convective diffusion.
• Derived mechanistic relationships between mass transfer coefficient and local surface curvature from fundamental physical laws.
• Utilized two coupled nonlinear ordinary differential equations to describe the dissolution process.

Main Results:

• The dissolution rate was theoretically shown to depend nonlinearly on surface curvature.
• The model successfully accounts for recrystallization in the bulk fluid.
• Model parameters can be determined using independent techniques, allowing evaluation of solid wettability.
• The proposed model demonstrated the significance of particle shape in fitting experimental dissolution data for theophylline monohydrate.

Conclusions:

• The developed mathematical model offers a simplified yet comprehensive approach to predicting drug dissolution from irregularly shaped particles.
• Particle shape is a critical factor influencing dissolution behavior and should be explicitly considered in predictive models.
• The model's ability to incorporate wettability and recrystallization provides a more complete understanding of the dissolution process.