Dynamic dissolution-/permeation-testing of nano- and microparticle formulations of fenofibrate

• Published in: European journal of pharmaceutical sciences 2017-01, Vol.96, p.20-27
• Main Authors: Sironi, Daniel, Rosenberg, Jörg, Bauer-Brandl, Annette, Brandl, Martin
• Format: Article
• Language: English
• Subjects: Diffusion; Dissolution/permeation; Drug Compounding; Drug Liberation; Dynamic; Enabling formulation; Fenofibrate - chemistry; Hypolipidemic Agents - chemistry; Intestinal Secretions - chemistry; Microparticle; Nanoparticle; Nanoparticles - chemistry; Particle Size; Permeability; Solubility; Solubilization; Supersaturation
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2016.09.001

The aim of the current study was to evaluate a dynamic dissolution-/permeation-system for prediction of gastrointestinal and absorption-behavior of two commercial fenofibrate formulations. To this end, both dissolution and barrier-flux were followed simultaneously for fenofibrate powder, a microparticle formulation (Lipidil® 200mg) and a nanoparticle formulation (LIPIDIL 145 ONE®) using a pair of side-by side diffusion cells separated by a cellulose hydrate membrane. Under such dynamic conditions, transient supersaturation arising from the nanoparticle formulation could be demonstrated for the first time. Furthermore, the dissolution-/permeation-system introduced here allowed for in-depth mechanistic insights: Biomimetic media, despite enhancing the apparent solubility of fenofibrate via micellar solubilization, did not increase permeation rate, irrespective whether the micro-/ or nanoparticle-formulation was tested. Nondissolved nano-/microparticles served as a reservoir helping to maintain high levels of molecularly dissolved drug, which in turn caused high and constant permeation rates. The micelle-bound drug may also serve as a drug-reservoir, yet of subordinate importance as long as there are nano-/microparticles present. Despite the limitations of the current experimental set-up, combined dissolution-/permeation-testing appears a valuable new tool to promote mechanistic understanding during formulation development. Last but not least, the in vitro dissolution and permeation behavior revealed here was in good qualitative agreement with human duodenal and plasma values reported in literature for the same formulations. [Display omitted]