App119 Solvate to Hydrate Conversion of Elacestrant Dihydrochloride Insights from DVS and XRPD
The application note reports a systematic investigation of the benzyl‑alcohol solvate form of Elacestrant dihydrochloride using Dynamic Vapor Sorption (DVS) and X‑ray Powder Diffraction (XRPD). Samples were subjected to controlled humidity cycles (0 %, 60 %, 92 % RH at 25 °C) and sorption‑desorption profiles were recorded with stringent equilibrium criteria. DVS revealed an anomalous mass loss between 80–90 % RH, indicating moisture‑induced crystallization and a solvate‑to‑hydrate conversion. Iso‑humidity exposures confirmed that the material remains polymorphically stable at low to moderate humidity, but transforms to a hemi‑pentahydrate phase at ≥90 % RH, as evidenced by new XRPD peaks. Quantitative analysis estimated the initial benzyl‑alcohol solvate content at ~16.5 % (≈0.84 mol solvate per mol API, effectively 1:1). The study concludes that the API is highly hygroscopic, requiring controlled storage and handling conditions, and demonstrates the complementary power of DVS and XRPD for characterising humidity‑driven solid‑state transitions.
Topics
Dynamic Vapor Sorption (DVS) Protocol and Humidity‑Triggered Mass Loss
Details of the DVS experimental design, sorption‑desorption cycles, equilibrium criteria, and the observed anomalous mass loss between 80–90 % RH.
Iso‑Humidity Exposure Coupled with XRPD Confirmation of Phase Transition
Description of fixed‑RH exposures (0 %, 60 %, 92 % RH) and the XRPD analysis that identified unchanged patterns at low RH and new peaks corresponding to a hemi‑pentahydrate at high RH.
Stoichiometric Determination of Benzyl‑Alcohol Solvate Content
Calculation of solvate mass loss, resulting solvate content (~16.5 %) and the inferred 1:1 benzyl‑alcohol‑to‑API stoichiometry.
Implications for Pharmaceutical Formulation, Storage, and Handling
Discussion of how the hygroscopic nature and rapid solvate‑to‑hydrate conversion at >90 % RH affect formulation strategies, packaging, and environmental controls.
Instrumentation and Methodological Overview
Overview of the DVS Resolution system and Bruker D8 ADVANCE XRPD instrument specifications, measurement parameters, and data acquisition settings.