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

Takácsné Novák, Krisztina and Tempfli, Dóra and Csicsák, Dóra and Völgyi, Gergely and Borbás, Enikő and Nagy, Zsombor Kristóf and Sinkó, Bálint (2019) Solubility analysis of venlafaxine hydrochloride polymorphs by shake-flask method and real time monitoring. ACTA PHARMACEUTICA HUNGARICA, 89 (2). pp. 88-96. ISSN 0001-6659

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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.

Item Type: Article
Subjects: R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában
R Medicine / orvostudomány > RS Pharmacy and materia medica / gyógyszerészet, gyógyászati eszközök
Depositing User: MTMT SWORD
Date Deposited: 30 Jul 2020 12:39
Last Modified: 16 May 2022 06:16

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