FaSSIF-V3, but not compendial media, appropriately detects differences in the peak and extent of exposure between reference and test formulations of ibuprofen.
BACKGROUND
The predictive capacity of in vitro dissolution tests using 50mM phosphate buffer at pH 6.8 to anticipate in vivo bioequivalence outcomes for highly permeable and poorly soluble weak acids has been questioned. In previous work, it was shown that using a lower buffer capacity could correctly distinguish the in vivo behavior of products containing ibuprofen free acid and those containing its salts.


OBJECTIVE
To assess whether adjustments in the composition of the medium, including matching the phosphate buffer concentration to the reported pH0 of dissolving ibuprofen free acid in bicarbonate buffer, as well as in the stirring rate, could detect differences in the extent and peak of exposure between reference and test formulations.


RESULTS
Using the recently revised fasted state simulated intestinal fluid (FaSSIF-V3) with reduced phosphate buffer concentration (5mM), it was possible to predict in vivo differences in peak and extent of exposure between test and reference formulations of ibuprofen.


CONCLUSIONS
For ibuprofen products, a modified Biopharmaceutics Classification System (BCS) based biowaiver dissolution test may be a way forward to approve generic products without having to perform pharmacokinetic studies. More studies with other BCS Class 2 weakly acidic compounds would be necessary to assess whether this approach could be applied more generally.
Brazilian Health Surveillance Agency (ANVISA), Division of Therapeutic Equivalence, Brasilia, Brazil; Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany.
Rodrigo
R
Cristofoletti
Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany. Electronic address: dressman@em.uni-frankfurt.de.
Jennifer B
JB
Dressman
D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000737:chemistry*; D012995:Solubility
D007052:Ibuprofen
Biopharmaceutics Classification System (BCS); Biowaiver; Capacity of detection; Dissolution; Surface pH