Bioinspired co-crystals of Imatinib providing enhanced kinetic solubility.

摘要: Realizing the full potential of co-crystals enhanced kinetic solubility demands a comprehensive understanding mechanisms dissolution, phase conversion, nucleation and crystal growth, complex interplay between active pharmaceutical ingredient (API), coformer co-existing forms in aqueous media. One blueprint provided by nature to keep poorly water-soluble bases solution is complexation with phenolic acids. Consequently, we followed bioinspired strategy for engineering molecule - Imatinib acid, syringic acid (SYA). The dynamics dissolution solution-mediated transformations were monitored Nuclear Magnetic Resonance (NMR) spectroscopy, providing mechanistic insights into 60 fold-increased long lasting concentrations achieved syringate as compared base mesylate. This effect was linked SYA's ability delay formation hydrate thermodynamically stable form media through metastable association SYA solution. Results from permeability studies evidenced that did not impact Imatinib's across membranes while suggesting improved bioavailability higher at biological barriers. These results reflect some degree hydrophobicity might be key extend hydrophobic APIs. Understanding how supersaturation can shaped selection an interactive may help achieving needed performance new water-soluble, slowly dissolving