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Article

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

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EA 4446 Bioactive Molecules and Medicinal Chemistry, SFR Santé Lyon-Est CNRS UMS3453-INSERM US7, Faculté de Pharmacie–ISPB, Université Claude Bernard Lyon, Université de Lyon, 18 avenue Rockefeller, F-69373, Lyon Cedex 8, France
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LAGEP UMR 5007, CNRS, Université Claude Bernard Lyon 1, Université de Lyon, 43 bd du 11 novembre, F-69622 Villeurbanne, France
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ISPB-Faculté de Pharmacie, Université Claude Bernard-Lyon 1, Université de Lyon, 8 avenue Rockefeller, F-69373, Lyon Cedex 8, France
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Centre Commun de RMN, Université Lyon 1, Université de Lyon, 43 boulevard du 11 Novembre, F-69622 Villeurbanne Cedex, France
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Author to whom correspondence should be addressed.
Pharmaceutics 2019, 11(1), 44; https://doi.org/10.3390/pharmaceutics11010044
Received: 14 December 2018 / Revised: 16 January 2019 / Accepted: 17 January 2019 / Published: 20 January 2019
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. View Full-Text
Keywords: tetrabenazine; deuteration; deuterated tetrabenazine; synthesis; stability; degradation impurities; acid medium; LC-MS; orodispersible film tetrabenazine; deuteration; deuterated tetrabenazine; synthesis; stability; degradation impurities; acid medium; LC-MS; orodispersible film
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MDPI and ACS Style

Ettouati, L.; Senta-Loys, Z.; Bourgeois, S.; Fenet, B.; Le Borgne, M.; Fessi, H. Behaviour of Tetrabenazine in Acid Medium: Reassessment and Impact on Formulation. Pharmaceutics 2019, 11, 44. https://doi.org/10.3390/pharmaceutics11010044

AMA Style

Ettouati L, Senta-Loys Z, Bourgeois S, Fenet B, Le Borgne M, Fessi H. Behaviour of Tetrabenazine in Acid Medium: Reassessment and Impact on Formulation. Pharmaceutics. 2019; 11(1):44. https://doi.org/10.3390/pharmaceutics11010044

Chicago/Turabian Style

Ettouati, Laurent, Zoé Senta-Loys, Sandrine Bourgeois, Bernard Fenet, Marc Le Borgne, and Hatem Fessi. 2019. "Behaviour of Tetrabenazine in Acid Medium: Reassessment and Impact on Formulation" Pharmaceutics 11, no. 1: 44. https://doi.org/10.3390/pharmaceutics11010044

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