Particle Size, Dose, and Confinement Affect Passive Diffusion Flux through the Membrane Concentration Boundary Layer

Area of Science:

• Pharmaceutical Sciences
• Physical Chemistry
• Chemical Engineering

Background:

• Traditional models often overlook particle dissolution within the concentration boundary layer (CBL) adjacent to semipermeable surfaces.
• Particle size and dose significantly influence drug behavior in pharmaceutical formulations.
• Understanding dissolution within the CBL is crucial for both in vivo and in vitro drug delivery assessments.

Purpose of the Study:

• To develop and validate a steady-state, particle-size, and dose-dependent dissolution-permeation model.
• To investigate the impact of particle dissolution within the CBL on drug flux across semipermeable membranes.
• To compare model predictions with experimental data for ibuprofen suspensions.

Main Methods:

• Development of a dissolution-permeation model incorporating particle dissolution within the CBL.
• Mass transfer experiments using an ultrathin large-area membrane diffusion cell with a silicone-based membrane.
• Testing the model with ibuprofen suspensions of varying particle sizes (6.6, 37.4, 240 μm) and doses.

Main Results:

• Experimental total flux measurements agreed with the proposed model's predictions.
• A measurable effect on flux was observed due to CBL thickness variations, dependent on particle size and suspension concentration.
• The dose-dependent total flux was up to 10% higher than predicted by the standard Higuchi-Hiestand model.

Conclusions:

• The proposed model accurately describes particle dissolution within the CBL and its effect on drug flux.
• Particle size and dose are critical factors influencing drug permeation, especially at lower concentrations.
• The model provides a more comprehensive understanding of drug dissolution and permeation compared to traditional models.