MacroFLUX

Achieve more realistic IVIVC modeling with better in situ concentration monitoring.

 

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 vitroin vivo correlation.

 

 

 

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