Behaviour of Tetrabenazine in Acid Medium: Reassessment and Impact on Formulation
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 aci...
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| Main Authors: | , , , , , |
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| Format: | Book |
| Published: |
MDPI AG,
2019-01-01T00:00:00Z.
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| Online Access: | Connect to this object online. |
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| Summary: | 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 <i>trans</i>-tetrabenazine with its unstable <i>cis</i> 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 <i>trans</i>-tetrabenazine with its <i>cis</i> 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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| Item Description: | 1999-4923 10.3390/pharmaceutics11010044 |