MacroFLUX

The Pion MacroFLUX™ apparatus can be used for conducting simultaneous dissolution-absorption studies. Such studies allow assessment of the complex interplay between solubility, permeability and dissolution rate in-vitro and provide valuable tools for understanding in vivo outcomes.

MacroFLUX™ can be used (i) during formulation development for optimising product performance and to evaluate whether certain formulation changes will affect the bio-performance of a certain drug product, (ii) during life-cycle management and product extensions to demonstrate bioequivalence, (iii) to compare brand and generic formulations to demonstrate bioequivalence, (iv) to compare test to reference formulations, (v) to ensure continuity of product quality (batch to batch consistency) and performance of the manufacturing process (in order to differentiate bioequivalent batches from non-bioequivalent batches within a range that guarantees comparable biopharmaceutical performance in vivo).

Formulated products, number of tablets/capsules dependent on type of study and required number of replicates. Pure API is required for calibration purposes.

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.

The MacroFLUX device consists of an absorption (receiver) chamber integrated with a permeation membrane, overhead stirrer and fiber optic (FO) UV probe that is inserted in to a modified cover of a standard 900 mL vessel of a USP II apparatus. The filter-supported artificial permeation membrane separates the dissolution (donor) compartment from the receiver compartment, containing pH 7.4 Pion Acceptor Sink Buffer. The dissolution compartment typically holds 900 mL of compendial or biorelevant dissolution buffer. The modified vessel cover allows fiber-optic UV probes to be 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. Issues typically encountered with external sampling of test solutions (e.g., sampling errors due to filter clogging, mechanical sipper malfunction, sample contamination, adsorption of compound to tubing) are minimized 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.