Case Study 615 Raman Polymorph Conversion
The case study reports a novel integration of a fiber‑optic Raman probe with a Dynamic Gravimetric Vapor Sorption (DVS) instrument to observe, in real time, the polymorphic conversion of D‑mannitol from the metastable δ form to the stable β form under various vapor environments. Pure α and δ polymorphs were prepared by controlled recrystallisation. Experiments were conducted at 25 °C with water vapor (25 % RH, 95 % RH) and at 45 °C with ethanol vapor (95 % P/P₀). Mass‑change data from DVS and concurrent Raman spectra were recorded. Findings show that β‑mannitol remains unchanged under water sorption/desorption cycles, while δ‑mannitol converts very slowly under 95 % RH water (≈65 h) contrary to earlier reports of rapid conversion. In ethanol vapor at 45 °C, δ‑mannitol converts faster, with increasing β‑peak intensity over 24 h, yet full conversion is not achieved. The combined Raman‑DVS approach demonstrates the capability to monitor vapor‑induced solid‑state transformations in situ, offering deeper insight into pharmaceutical ingredient stability.
Topics
Fiber‑Optic Raman Probe Integrated with Dynamic Vapor Sorption for Real‑Time Polymorph Tracking
Design and implementation of a dual‑adapter DVS stand that houses a fiber‑optic Raman probe, enabling simultaneous mass‑change measurement and Raman spectral acquisition.