Recent Publication:

Novel Pharmaceutical Cocrystals and Salts of Bumetanide

New crystalline forms of bumetanide, namely four cocrystals, two salts and one salt-cocrystal were crystallized. Urea and lactams such as valerolactam, caprolactam, N-methyl caprolactam formed cocrystals with bumetanide whereas 4-aminopyridine gave a salt. Piperazine afforded a salt hydrate and 5-flurocytosine gave a salt-cocrystal. The supramolecular synthons in bumetanide-lactam cocrystals are amide dimer between drug and coformer, and acid homo dimer between bumetanide molecules. In bumetanide salts, the acid proton is transferred from bumetanide to coformer amine whereas in bumetanide salt-cocrystal proton transfer and free acid was observed in the crystal structure. Similar to the cytosine salt-cocrystal of bumetande, fluorocytosine also gave salt-cocrystal adduct. The acid proton of bumetanide is transferred to 2-amino pyridine base of cytosine as a salt, and on the other side of drug molecule the sulfonamide interacts with the syn amide part of cytosine. Furthermore, solubility, dissolution and diffusion membrane permeability experiments were performed on all new solid forms. Piperazine salt shows high dissolution and permeability cross-over when compared to other binary forms of bumetanide.

Authors:  Suryanarayana Allu, Geetha Bolla, Srinu Tothadi, Ashwini K Nangia*

 Publication date : Dec 16th, 2019