Behaviour of Tetrabenazine in Acid Medium: Reassessment and Impact on Formulation

Abstract : Thorough studies of previous analytical stress data of tetrabenazine, a dopamine depleting agent, showed a potential susceptibility to acidic conditions. Hence, the behavior of tetrabenazine acidic solutions was studied by LC-MS and NMR spectroscopy. Reverse-phase LC-MS analysis of tetrabenazine acidic aqueous solutions consistently showed a main lipophilic impurity in a proportion of 15 to 20%. NMR spectroscopy studies did not allow to completely ascertain its structure. However, we hypothesize an interconversion of trans-tetrabenazine with its unstable cis isomer via an open isoquinolinium intermediate. Evaluation of tetrabenazine integrity in orodispersible films was reassessed in light of these observations after formulation and during stability study. Even if interconversion of trans-tetrabenazine with its cis isomer was observed in orodispersible films containing tetrabenazine, this phenomenon seems not to have any consequences for the overall tetrabenazine bioavailability.
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Pharmaceutics, MDPI, 2019, 11 (1), pp.44. 〈10.3390/pharmaceutics11010044〉
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Contributeur : Laurent Ettouati <>
Soumis le : dimanche 20 janvier 2019 - 12:03:12
Dernière modification le : vendredi 8 février 2019 - 01:19:06

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Laurent Ettouati, Zoé Senta-Loys, Sandrine Bourgeois, Bernard Fenet, Marc Le Borgne, et al.. Behaviour of Tetrabenazine in Acid Medium: Reassessment and Impact on Formulation. Pharmaceutics, MDPI, 2019, 11 (1), pp.44. 〈10.3390/pharmaceutics11010044〉. 〈hal-01987081〉

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