Achieve more realistic IVIVC modeling with better in situ concentration monitoring.
Are you desperately seeking an in vitro test to rank formulations’ absorption potential before animal studies?
Are you tired of trying to correlate dissolution results to in vivo absorption?
Are you sick of failing trials/studies due to a lack of good in vitro tools/data for in vivo prediction?
In many cases, dissolution experiments alone cannot correctly predict the in vivo response to drug products due to the complicated interplay of solubility and permeability in complex media. Pion’s MacroFLUX device extends the utility of in situ concentration monitoring to improve assessment of absorption potential and more realistic IVIVC modeling.
Introducing a stirred absorption chamber into the traditional USP I and II apparatus allows this type of testing to be done in vitro through the use of the MacroFLUX dissolution system. The USP vessel is the donor compartment, allowing for the volumes needed to test finished dosage forms under sink conditions. Using in situ fiber optic UV detection in both the donor and receiver provides the required data density for accurate assessment of transmembrane FLUX.
The patented MacroFlux technology provides real time IVIVC prediction as the next step in Pion FLUX family of products.
Case Study: Using MacroFLUX to compare innovator and generic product
Dissolution profile (on the left), in vitro appearance profile (in the middle), and in vivo appearance (on the right) of active ingredient from different formulations.
The dissolution and flux results of the innovator and generic product 40 mg tablets were compared. The generic showed a slower release kinetics than the innovator, though reached the same maximum concentration after 110 min. After media change, the flux from the generic product was found to be
0.240 ± 0.011 µg/(cm2*min), which is only 71% of the flux of the innovator (0.337 ± 0.028 µg/(cm2*min)). This in vitro result showed excellent correlation with the in vivo data from bioequivalence studies where the appearance rate or the drug in blood from the generic was 72% of the rate from the innovator.
The in vivo predictive power of the simultaneous dissolution-absorption test was demonstrated by comparing the in vitro fluxes to in vivo rate of appearance in blood of innovator and generic formulation of the product. The performance of the generic product was 71% of the innovator in vitro, while 72% in vivo, showing excellent in vitro–in vivo correlation.
A MacroFLUX Accessory for Assessment of Absorption Potential in Biorelevant Volumes
Pion’s BioFLUX device is an addition to the Pion’s flux device family. It further extends the utility of in situ concentration monitoring to improve the assessment of the absorption potential and more realistic IVIVC modeling while enabling to work with 200–250 mL dissolution volumes.
The smaller volume USP-like vessel is the donor compartment, allowing for the volumes needed to test finished dosage forms under biorelevant conditions. Using in situ fiber optic UV detection in both the donor and receiver chambers provides the required data density for accurate assessment of transmembrane flux.
Materials and Reagents
Rainbow Fiber Optic System (recommended R2D6 or R2D8), AuPRO Software, Rev 5.5 or higher
Pion Dip Probe, 14 cm RH threads (“donor probes”)
P/N 112298 (1‐3 items)
Probe Tip, 2 mm path, RH Threads (3 items)
Erweka Dissolution Tester (Dissolution Bath)
MacroFLUX Stirrer Assembly
MacroFLUX Benchtop Controller Assembly
MacroFLUX Vessel Cover with Evaporation Plug (pre‐assembled)