Solubility analysis of venlafaxine hydrochloride polymorphs by shake-flask method and real time monitoring

Authors

  • Krisztina Takács-Novák Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary
  • Dóra Tempfli Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary
  • Dóra Csicsák Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary
  • Gergely Völgyi Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary
  • Enikő Borbás Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Budapest, Hungary
  • Zsombor K. Nagy Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Budapest, Hungary
  • Bálint Sinkó Pion Inc. Billerica, Massachusetts, United States of America

DOI:

https://doi.org/10.33892/aph.2019.89.88-96

Keywords:

solubility-pH profile, polymorphs, shake-flask method, µDISS Profiler, venlafaxine

Abstract

Aims: The aqueous solubility of two polymorphic forms of venlafaxine hydrochloride was investigated.

Methods: The pH-dependent solubility (SpH) over a wide pH range was measured by saturation shake-flask (SSF) method at 25 °C. The solubility of the free base form was depicted by the intrinsic solubility (So). To identify the solid form present at the solubility equilibrium, X-ray powder diffraction (XRPD) and Raman spectroscopy was carried out. The dissolution was studied using real time concentration monitoring applying fiber optic UV probes.

Results: No difference was found in the SpH values of Form I and Form II, in the pH range 7.5-12. Solid phase isolated from pH 10-12 suspensions was identified as free base by XRPD and Raman spectroscopy. Precipitates separated from pH 7-8 samples were also identical product. The transition of polymorphs to the free base was supported by the real time dissolution analysis.

Conclusion: In this study we demonstrated a good agreement of equilibrium solubility measured by SSF method and in-situ UV fiber optic method. µDISS ProfilerTM has the advantage to provide much more information about dissolution process; with this approach the dissolution kinetic, the supersaturation and the time needed to reach the equilibrium can be easily monitored.

 

Published

2019-08-01

How to Cite

(1)
Takács-Novák, K.; Tempfli, D.; Csicsák, D.; Völgyi, G.; Borbás, E.; Nagy, Z. K.; Sinkó, B. Solubility Analysis of Venlafaxine Hydrochloride Polymorphs by Shake-Flask Method and Real Time Monitoring. Acta Pharm Hung 2019, 89, 88-96.

Issue

Vol. 89 No. 2 (2019)

Section

Original Research Articles

Copyright (c) 2019 Acta Pharmaceutica Hungarica

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APH is published as a diamond open-access journal under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

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