Impact of drug incorporation into micelle on reduced griseofulvin and meloxicam permeation across a hollow fiber membrane

• Published in: Journal of pharmaceutical sciences 2025-01, Vol.114 (1), p.402-415
• Main Authors: Patel, Roshni P., Taylor, Lynne S., Polli, James E.
• Format: Article
• Language: English
• Subjects: Antifungal Agents - administration & dosage; Antifungal Agents - chemistry; Antifungal Agents - pharmacokinetics; Equilibrium coefficient; Flux; Free drug; Griseofulvin; Griseofulvin - chemistry; Griseofulvin - pharmacokinetics; Meloxicam - pharmacokinetics; Membranes, Artificial; Micelle; Micelles; Permeability; Sodium Dodecyl Sulfate - chemistry; Solubility; Surface-Active Agents - chemistry; Surfactant; Thiazines - administration & dosage; Thiazines - chemistry; Thiazines - pharmacokinetics; Thiazoles - chemistry; Thiazoles - pharmacokinetics
• ISSN: 0022-3549; 1520-6017; 1520-6017
• DOI: 10.1016/j.xphs.2024.10.017

A hollow fiber membrane (HFM) was previously characterized as a potential permeation component of a dissolution/permeation system. Two objectives were to assess the impact of micellization on drug permeation across HFM and identify a preferred permeation model from three models: permeation from only free drug, permeation from both free drug and micelle-bound drug, and permeation with enhancement from micelle shuttling. HFM studies were conducted under unsaturated drug conditions, using griseofulvin and the more hydrophilic drug meloxicam, with and without surfactant [sodium lauryl sulfate, polysorbate 80, and polyoxyethylene (10) lauryl ether]. Griseofulvin was micelle incorporated to a greater extent than meloxicam, such that griseofulvin flux decreased to a greater extent than for meloxicam. The griseofulvin permeation model from only free drug was rejected, since griseofulvin flux required free drug to be about 5–20 fold higher in HFM flux studies than supported by solubility studies, depending on surfactant. Permeation from both free griseofulvin and micelle-bound griseofulvin successfully accommodated observed flux, where micelle permeability was about 5-fold lower than free drug permeability for HFM with 10 KDa MWCO. Permeation with enhancement from micelle shuttling was not the preferred explanation, although the model accommodated flux data and provided aqueous boundary layer thicknesses similar to other setups.