Balint Sinko
Pion Inc., USA
Title: Application of simultaneous dissolution-absorption apparatus for screening formulations before bioequivalence studies
Biography
Biography: Balint Sinko
Abstract
For generic drug development traditional dissolution tests have been used in the pharmaceutical industry to compare performance of different drug product formulations before conducting bioequivalence studies, even though the in vivo predictive power of these tests are questionable. When a poorly water-soluble API is formulated to enhance its dissolution, additives have an effect not only on dissolution, but also on flux through the membrane. The aim of this study was to demonstrate that a simultaneous dissolution-absorption test can be used as a predictive tool before bioequivalence studies are conducted. Telmisartan tablets were tested using MacroFLUX. Receiver chamber integrated with permeation membrane, overhead stirrer and UV probe was inserted in the standard 900 mL vessel of USP II apparatus.
An artificial membrane with 3.8 cm2 area was separating the dissolution compartment from the receiver compartment containing 15 mL of pH7.4 buffer. The dissolution and flux results of the brand name (Micardis) and generic (Actavis) Telmisartan 40 mg tablets were compared. Actavis showed a slower release kinetics than Micardis, though reached the same maximum concentration after 110 min. 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 brand name (0.337 ± 0.028 µg/(cm2*min)). This in vitro result showed excellent correlation with the in vivo data from bioequivalence studies, where the appearence rate or the drug in blood from Actavis was 72 % of the rate from Micardis. 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 brand name and generic formulation of telmisartan.