Next Article in Journal
Human Olfactory Bulb Neural Stem Cells (Hu-OBNSCs) Can Be Loaded with Paclitaxel and Used to Inhibit Glioblastoma Cell Growth
Previous Article in Journal
Interactions of Self-Assembled Bletilla Striata Polysaccharide Nanoparticles with Bovine Serum Albumin and Biodistribution of Its Docetaxel-Loaded Nanoparticles
Article Menu
Issue 1 (January) cover image

Export Article

Open AccessArticle

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

1
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
2
LAGEP UMR 5007, CNRS, Université Claude Bernard Lyon 1, Université de Lyon, 43 bd du 11 novembre, F-69622 Villeurbanne, France
3
ISPB-Faculté de Pharmacie, Université Claude Bernard-Lyon 1, Université de Lyon, 8 avenue Rockefeller, F-69373, Lyon Cedex 8, France
4
Centre Commun de RMN, Université Lyon 1, Université de Lyon, 43 boulevard du 11 Novembre, F-69622 Villeurbanne Cedex, France
*
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
  |  
PDF [913 KB, uploaded 22 January 2019]
  |  

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. 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
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Pharmaceutics EISSN 1999-4923 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top