New Polymorphs of Huperzine A: Preparation, Structures, and Physicochemical Properties of Anhydrous Crystal Forms

Abstract

Three new polymorphs (forms I, II, and III) of natural cholinesterase inhibitor Huperzine A were discovered through a comprehensive polymorph screening experiment. Their structures were elucidated by single-crystal structure analysis and characterized by powder X-ray diffraction, Fourier transform-infrared spectroscopy, and DXR Raman microscope. The physicochemical properties of these new forms were investigated by thermal analysis (TGA and DSC) and dynamic vapor sorption (DVS) isotherms. The powder dissolution rates were compared with the marketed monohydrate form. Thermodynamic stability, phase transformation, E–T diagram, and drugability properties are also discussed in detail.