Multicomponent System of NPS-1034, an Orally Administered Lung Cancer Drug Candidate, with Sulfonic Acids and Solid State Characterization

NPS-1034 is a drug candidate targeted
for the regulation of c-MET/AXL
receptor tyrosin kinase activity. NPS-1034 was developed to improve
efficacy and reduce toxicity by targeting c-MET/AXL related signaling
pathways. However, NPS-1034 is practically insoluble in almost all
organic solvents as well as aqueous media (pH 1, 4.5, and 7.5). We
attempted to improve the physicochemical properties of NPS-1034 by
forming multicomponent systems with a wide variety of sulfonic acids
including methanesulfonic acid, 1,2-ethanedisulfonic acid, p-toluenesulfonic acid, and camphorsulfonic acid. Solid
state characterization of NPS-1034 salts and amorphous with sulfonic
acids was conducted, and the crystal structures of four salts and
NPS-1034 were compared and investigated. Sulfonic acid salts of NPS-1034
decreased the melting point of NPS-1034 as much as −155.43
°C. Solubilities of NPS-1034 and salts of NPS-1034 were measured
to develop lipid-based formulation for the GLP toxicity study. Solvents
studied include oleic acid, poly­(ethylene glycol) 400, and ethanol.
Solubility of amorphous of NPS-1034 with camphorsulfonic acid showed
a significant increase in all three solvents. This work will give
some insight into how various types of sulfonic acids interact with
pharmaceutically important compounds containing the pyrrolepyridine
moiety.