Application of MacroFLUXTM Apparatus for Screening Formulations Before Bioequivalence Studies

Konstantin Tsinman, Scientific R&D, Pion Inc, Billerica, USA

For generic drug development traditional (USP) dissolution tests have been used in the pharmaceutical industry to compare performance of different drug product formulations before or instead of conducting bioequivalence studies. Although dissolution tests provide a simple way of testing formulations, the in vivo predictive power of these tests are questionable. Namely, when a poorly water-soluble API is formulated to enhance its dissolution, additives, such as surfactants and polymers have an effect not only on dissolution profile, but also on flux through the membrane. The aim of this study was to represent the importance of simultaneous dissolution-absorption studies using MacroFLUXTM apparatus before conducting bioequivalence studies.

The dissolution and flux results of the brand name (Micardis) and generic (Pritor) Telmisartan 40 mg tablets were compared (Figure 2). Both formulations showed slow release kinetics in SGF and instant dissolution after media convertion to FaSSIF full with the final concentration around 35 µg/mL (more than 90% of the API dissolved). In the first 30 minutes of the experiments the concentration of the API in the acceptor chamber was under the detection limit (~ 0.1 µg/mL). After media change in the time interval of 50-120 minutes the flux through membrane was found to be 0.337 ± 0.028 µg/(cm2 *min) in case of the brand and 0.308 ± 0.014 µg/(cm2*min) in case of the generic product. In comparison the initial flux from unformulated API at the same load in the donor compartment was 0.120 ± 0.016 µg/(cm2 *min) and it was decreasing due to precipitation of API in FaSSIF.

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Short Biography of Presenting Author

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