Ranking Itraconazole Formulations Based on the Flux through Artificial Lipophilic Membrane

Abstract

It was demonstrated that in vitro flux measurements using lipophilic artificial membranes could correctly reproduce the rank order of PK results for ITZ formulations. The drop in flux over time for solid dispersions could be backed by experimental indications of crystallization.

Preparation and Evaluation of Resveratrol-Loaded Composite Nanoparticles Using a Supercritical Fluid Technology for Enhanced Oral and Skin Delivery

“…However, the3.0-fold in vivo increase in AUC 0→12 h for trans -resveratrol/HPMC/poloxamer 407 (1:4:1) nanoparticles relative to micronized trans -resveratrol more closely follows the in vitro flux enhancement. Similar to a previously reported method [28], we performed regression analysis between the total amount of trans -resveratrol absorbed at 240 min in flux measurements and in in vivo AUC 0–12 h . At 240 min, the amounts of permeated trans -resveratrol in the receiver cell were 89.6 ± 2.0 μg for micronized trans -resveratrol, 136.4 ± 2.2 μg for drug/HPMC (1:4), 139.1 ± 2.9 μg for drug/HPMC (1:5), 209.7 ± 4.2 μg for drug/HPMC/gelucire 44/14 (1:4:1), 260.9 ± 8.2 μg for drug/HPMC/TPGS (1:4:1), and 279.5 ± 5.3 μg for drug/HPMC/poloxamer 407 (1:4:1), with the same ranks observed for in vivo AUC 0→12 h .…”

“…To compare trans -resveratrol flux between different composite nanoparticles prepared by an SAS process and to evaluate the correlation between in vitro flux data and in vivo pharmacokinetic data for trans -resveratrol, a flux measurement study of trans -resveratrol was carried out using a miniaturized dissolution–permeation apparatus (μFLUX TM apparatus, Pion Inc., Billerica, MA, USA) [28]. This apparatus contains a horizontal diffusion cell composed of a donor cell, membrane, and receiver cell.…”

On the Usefulness of Two Small-Scale In Vitro Setups in the Evaluation of Luminal Precipitation of Lipophilic Weak Bases in Early Formulation Development

“…Stirring was provided by cross-bar magnetic stirrers in both chambers and was set at 150 rpm throughout the experiment. The acceptor chamber was filled with 20 mL of acceptor sink buffer (ASB) throughout the experiment, to maintain sink conditions during the experiment [15]. The donor chamber was initially filled with 15 mL of dilute HCl at pH 2 and drug was manually introduced to begin the experiment.…”

“…Another small-scale in vitro method for evaluating absorption of drug in the small intestine is by using an artificial membrane. The µFLUX (Pion Inc., Billerica, MA, USA) is a small-scale dissolution-permeation (D-P) system consisting of four pairs of two chambers setups separated by an artificial biomimetic membrane [15][16][17]. As the system has four pairs of chambers, experiments can be run in parallel, facilitating a high experimental throughput.…”

“…Calculation of in vivo precipitation rates was not the intended primary purpose of the µFLUX setup and, therefore, it has not been optimised for this application. It has previously been shown to have other applications during drug development, such as examining the differences in bioavailability of different formulations [15,16] or assessing the effects of a raised gastric pH [17].…”