Salts and Polymorph Screens For Bedaquiline
Salts and Polymorph Screens For Bedaquiline

Abstract

Bedaquiline is used to treat multi-resistant tuberculosis (TB) in adults. The fumarate salt is the commercially available option, so, to make the increase accessibility to the product, new salts were screened. This is especially important for low income economies, which have higher TB disease burden. The current experiments focus on the isolation of acetate, benzoate, benzenesulfonate, hydrobromide, succinate, hydrochloride, tartrate, lactate, maleate, malate, and mesylate salts of Bedaquiline.
Potential salts were screened by dissolving 1:1 ratios of the individual salt formers and Bedaquiline base (30 mg, 0.055 millimoles) in different solvents. To determine the most stable forms for the new salts, polymorph screen were conducted in solvents of various polarities. X-ray diffraction techniques, together with other spectroscopic and thermal analysis were employed to characterize the salts.
Structural identities for benzoate, maleate, hydrochloride, mesylate and besylate salts of bedaquiline were confirmed by powder X-ray diffraction patterns. TGA and DSC thermal analysis were further used to characterize the benzoate salts. Polymorph screen conducted on the salts suggested no presence of additional polymorphs at the current stage
A salt screen successfully generated five salts of Bedaquiline, namely benzoate, maleate, hydrochloride, besylate and mesylate.