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

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.

Understanding the pH Dependence of Supersaturation State—A Case Study of Telmisartan

“…Solid-state characterizations must also be performed at the end of the measurement, since in the presence of a solvent changes in the structure of the solid compound may influence the measurement results (salt formation, polymorphic transformation, crystallization) [18]. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Raman spectroscopy are the most commonly used techniques for solid-state analysis [19][20][21]. One of the main disadvantages of the SSF method is that it requires phase separation, which can be performed by sedimentation, centrifugation, or filtration.…”