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Mechanisms and Extent of Enhanced Passive Permeation by Colloidal Drug Particles
Akshay Narula1, Rayan Sabra1, Na Li1,2
1Department of Pharmaceutical Sciences, University of Connecticut, 69 North Eagleville Road Unit 3092, Storrs, Connecticut 06269, United States.
Molecular Pharmaceutics
|August 23, 2022
Summary
Nanosized drug particles enhance bioavailability by improving passive permeation. Flux depends on particle size and drug partitioning, with mass transfer occurring via dissolved drug molecules.
Area of Science:
- Pharmaceutical Sciences
- Materials Science
Background:
- Nanosized drug particles, including nanocrystals and amorphous aggregates, show promise for enhancing the bioavailability of poorly soluble drugs.
- The enhanced bioavailability is not solely explained by increased solubility from particle size reduction.
Purpose of the Study:
- To investigate the mechanisms and extent of enhanced passive permeation mediated by drug particles.
- To evaluate the influence of particle size, drug partitioning, and formulation conditions on transmembrane flux.
Main Methods:
- Utilized Franz diffusion cells with lipid-infused membranes to assess transmembrane flux.
- Investigated the impact of stirring rate, receiver buffer conditions, and particle size.
- Conducted mass transport analyses to calculate flux enhancement.
Main Results:
- Flux enhancement was dependent on particle size and the drug's partitioning behavior between the receiver solution and the membrane.
- A flux plateau was observed at high particle concentrations, indicating mass transfer occurs through molecularly dissolved drug.
- Mass transport models accurately predicted flux enhancement for various drugs and conditions.
Conclusions:
- Passive permeation enhancement by drug particles is influenced by particle size and drug-specific partitioning characteristics.
- Mass transfer of amorphous drug particles is limited to the molecularly dissolved fraction.
- The findings support improved bioavailability prediction and formulation design for colloidal drug particles.
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