<![CDATA[Solid-state properties of active pharmaceutical ingredients are important in dosage-form development because phase transformation, hydrate or solvate formation, and crystal habit modification can influence manufacturing performance and physicochemical properties. Amodiaquine hydrochloride (AQ) is an antimalarial active pharmaceutical ingredient used in artemisinin-based combination therapy and is known to occur as a hydrated crystalline form. This study evaluated the solid-state characteristics of AQ and the effects of recrystallization, heating, and milling on its crystal structure, crystallinity, thermal behavior, and morphology. AQ samples before and after treatment were characterized using powder X-ray diffraction (PXRD), thermal analysis, Fourier-transform infrared spectroscopy (FT-IR), hot-stage/polarized-light microscopy, scanning electron microscopy (SEM), and single-crystal X-ray diffraction. Recrystallization from methanol, chloroform, and acetone did not produce new PXRD peaks or meaningful changes in crystal habit. Heating at 170 °C for 1 hour produced thermal changes consistent with dehydration, without evidence of polymorphic conversion. Milling for 10, 30, and 60 minutes reduced crystallinity and thermal enthalpy, indicating lattice defects rather than formation of a new polymorph. FT-IR spectra retained the main absorption bands after thermal and mechanical treatments, suggesting that no major spectroscopic changes indicating chemical degradation were detected. Single-crystal analysis confirmed a monoclinic crystal system with space group P21/c, consistent with amodiaquine hydrochloride dihydrate. Overall, AQ maintained the same crystalline phase under the evaluated recrystallization, heating, and milling conditions, although hydration-state changes after heating should be interpreted cautiously.]]>
