Solubility Enhancement of Lumefantrine by Co-crystallization Method Using Amino Acids as Potential Coformers

Lumefantrine, an anti-malarial drug, has a slow onset of action, erratic absorption, and low bioavailability owing to its poor water solubility. The present study explored the possibility of crystal engineering to improve the solubility of lumefantrine.

Solvent drop grinding method was used to prepare the cocrystals of lumefantrine. Seven amino acids were selected as coformers. The best coformer was selected using Dunnett's test on solubility data. Solubility was estimated at pH 1.2, 4.5, and 6.8. The drug dissolution medium was determined based on Gibbs' free energy and the lowest dose-solubility ratio. The best cocrystals were evaluated for compatibility, physical, surface, and thermal properties, and stability studies.

The screening study of coformers revealed that isoleucine and valine were the best. Solubility studies at three different pHs revealed that the valine cocrystals of lumefantrine exhibited significantly greater solubility than the isoleucine-lumefantrine cocrystal. Nuclear magnetic resonance spectroscopy proved the formation of a non-covalent bond between valine and the drug. Surface characterization and thermal analysis revealed the conversion of the drug from crystalline to amorphous form, supporting the observed solubility enhancement of lumefantrine. The cocrystal of lumefantrine and valine in a 1:2 ratio showed the best performance, and its stability was also confirmed.

It can be concluded that cocrystals of the drug and valine at a 1:2 stoichiometric ratio can serve as a promising cocrystal of the drug for the development of dosage forms with high bioavailability.