Salt Formation and Crystal Forms of Pyronaridine Phosphate salts: Single Crystal X-Ray Structures of New Triphosphate crystalline forms and Structural Proof of a Hemiheptaphosphate salt

<jats:p>Pyronaridine is an antimalarial API first developed in the 1970s and is sold as a material historically described as the tetraphosphate salt, which is said not to exhibit polymorphism. Our study indicates that there are multiple salt forms of pyronaridine phosphate and that no structurally confirmed true tetraphosphate has yet been reported. Single-crystal X-ray structures of crystalline forms reveal several triphosphate forms (including hydrated and solvate forms) and one hemiheptaphosphate salt (with 3.5 phosphate units per molecule of pyronaridine). Other crystalline forms have been obtained but have not yet been fully characterized by single-crystal X-ray crystallography and are therefore tentatively assigned as probable hydrated hemiheptaphosphate-related forms. The relevance of these different forms to API manufacturing and stability is discussed.</jats:p>