MicroFLUX

Introduction

The MicroFLUX™ apparatus developed by Pion works to assess the in vitro absorption potential (transmembrane flux) of prototype formulations using small-scale experiments. It is frequently used during the early stages of development for optimising prototype formulations and to determine which excipients will improve the expected bio-performance of poorly soluble candidate API molecules. The impact of excipients on drug behaviour when conducting these simultaneous dissolution-absorption studies provides an understanding of the complex interplay between solubility, permeability and dissolution rate in-vitro and establishes the MicroFLUX as a valuable tool for ranking in-vivo outcomes.

Sample submission details

Prototype formulations, number dependent on type of study and required number of replicates. Typical required dose is scaled to the Biopharmaceutics Classification System, i.e., compound weight = estimated human dose multiplied by (low-volume, 20 mL/BCS volume, 250 mL).

Key deliverable

Acceptor drug concentrations and flux values across the membrane. Additionally, the percent release (%mass/time) of drug for each donor vessel is determined showing release profiles and dissolution performance. A full study report is provided which gives a detailed overview of the methods and results obtained.

Experiment overview

The MicroFLUX device consists of a low-volume absorption (receiver) chamber separated from a low-volume donor chamber with a biomimetic gastrointestinal tract permeation membrane. The receiver chamber contains pH 7.4 Pion Acceptor Sink Buffer and the donor dissolution compartment holds aqueous or biorelevant dissolution buffer. The Microflux chambers are used with the µDiss Profiler platform to provide temperature control and magnetic stirring. Fiber-optic UV probes are positioned in both the donor and receiver compartments allowing real-time dissolution and absorption concentration monitoring in both chambers. Concentration monitoring is enabled by connecting the fiber optic UV probes to the Rainbow Dynamic Dissolution Monitor® instrument (Pion Inc.).

The use of in situ fibre-optic dip-probe UV analysis overcomes many of the challenges of traditional testing methods which use external sampling of the test solutions, since the concentration measurements are performed directly in the dissolution media, with processed results plotted in “real time.” Interference due to background turbidity is minimized when needed by a spectral second derivative method. Spectral scans (200 – 720 nm) of all channels takes less than five seconds. The PDA baseline noise is ±0.0002 absorbance units.

Resources

"Pion Biphasic Dissolution PBPK Modelling and Lipolysis Assays" Webinar

Evaluating side‐by‐side diffusion models for studying drug supersaturation in an absorptive environment: a case example of fenofibrate and felodipine

Degree and Extent of Supersaturation of Amorphous Pharmaceuticals and Their Flux through Lipophilic Membrane

Using Biorelevant Flux Measurements for Prediction of Fraction Absorbed for the Drug Products of Poorly Soluble Compounds

From Traditional Dissolution to In Vivo Predictive Flux Measurements

Prediction of Bioequivalence and Food Effect Using Flux- and Solubility-Based Methods

Biorelevant Flux Measurements And Prediction Of Fraction Absorbed For The Drug Products Of Poorly Soluble Compounds

Effect of Formulation Additives on Drug Transport through Size-Exclusion Membranes

Investigating the driving force of membrane transport of carvedilol from supersaturated solutions achieved by ...

In vitro methods to assess drug precipitation in the fasted small intestine - a PEARRL review

in vitro dissolution-absorption evaluation of an electrospun cyclodextrin-based formulation of aripiprazole using µFLUX

Investigation and Mathematical Description of the Real Driving Force of Passive Transport of Drug Molecules from Supersaturated Solutions

Ranking Itraconazole Formulations Based on the Flux through Artificial Lipophilic Membrane

Video: Use of Flux Measurements in Lieu of In Vitro Dissolution to Assess the Complex Interplay Between Solubility, Permeability and Formulation Effects

Degree and Extent of Supersaturation of Amorphous Pharmaceuticals and Their Flux through Lipophilic Membrane

Differentiating Itraconazole Formulations Based on the Flux through Artificial Lipophilic Membrane

FLUX Measurements using Pion µFLUX™ and MacroFLUX™ Devices

µFLUX Brochure

Differentiating itraconazole formulations based on the flux through artificial lipophilic membranes

Using flux experiments through artificial lipophilic membranes for predicting food effect for BCS Class 2 Compounds

Degree and Extent of Supersaturation of Amorphous Pharmaceuticals and Their Flux through Lipophilic Membranes

In Situ Method for Monitoring Free Drug Concentration Released from Nanoparticles

Dissolution-Permeability Apparatus with Integrated In Situ Concentration Monitoring of both Donor and Receiver Compartments

Real Time Monitoring of Dissolution, Supersaturation and Precipitation Processes in Dynamically Changing Biorelevant Media

Supersaturation and Transmembrane Flux of Meloxicam

Nanoparticle Formulation of Gresiofulvin

Universal Potentiometric Sensors Fast Determination of Free Ionized Drug Concentration in Micellar Solutions

Application of In Situ Potentiometric Sensors to Study Dissolution-Precipitation Behavior of Electrospray-Generated Loperamide Nanoparticles

Cyclodextrin-Based Orally Fast Dissolving Drug Delivery System of Aripiprazole and Its In Vitro Dissolution-Permeation Testing Using µFLUX

Dissolution, Free Drug Concentration and Permeability of Crystalline Nanoparticle Formulation Study Using In Situ Fiber Optic and Potentiometric Techniques

Interplay between Ketoconazole Cocrystal Supersaturation and Trans-membrane Flux Behavior In Simulated Intestinal Fluids

Effect of simulated mucus environment on the supersaturation of carvedilol and its flux through artificial lipophilic membranes

Study of Danazol Cocrystal using Trans-membrane Flux Measurements

Estimating food effect on drug absorption using flux experiments through artificial lipophilic membranes