TY - JOUR
T1 - Cocrystallization of Trimethoprim and Solubility Enhancement via Salt Formation
AU - Zheng, Qixuan
AU - Unruh, Daniel
AU - Hutchins, Kristin
N1 - Funding Information:
K.M.H. gratefully acknowledges financial support from Texas Tech University. We acknowledge Prof. Sindee Simon and Dr. Yung Koh for assistance in running the samples for TGA and DSC analysis.
Publisher Copyright:
© 2021 American Chemical Society.
PY - 2021/1/28
Y1 - 2021/1/28
N2 - Trimethoprim (TMP) is an active pharmaceutical ingredient with poor aqueous solubility. Here, we describe the cocrystallization of TMP with five co-formers, three bipyridines and two monopyridines. Cocrystallization of TMP with the bipyridines yields neutral cocrystals, and while both components are present in the lattice, they do not interact with each other via any strong intermolecular forces. Conversely, cocrystallization of TMP with the monopyridines yields salts, and included water or solvent molecules that play a key role in supramolecular assembly. Moreover, the salts exhibit significantly higher aqueous solubility than that of TMP. Two solids feature a compound on the Generally Recognized as Safe list, making them promising as ionic pharmaceutical cocrystals.
AB - Trimethoprim (TMP) is an active pharmaceutical ingredient with poor aqueous solubility. Here, we describe the cocrystallization of TMP with five co-formers, three bipyridines and two monopyridines. Cocrystallization of TMP with the bipyridines yields neutral cocrystals, and while both components are present in the lattice, they do not interact with each other via any strong intermolecular forces. Conversely, cocrystallization of TMP with the monopyridines yields salts, and included water or solvent molecules that play a key role in supramolecular assembly. Moreover, the salts exhibit significantly higher aqueous solubility than that of TMP. Two solids feature a compound on the Generally Recognized as Safe list, making them promising as ionic pharmaceutical cocrystals.
UR - http://www.scopus.com/inward/record.url?scp=85100693693&partnerID=8YFLogxK
U2 - 10.1021/acs.cgd.0c01197
DO - 10.1021/acs.cgd.0c01197
M3 - Article
VL - 21
SP - 1507
EP - 1517
JO - Crystal Growth & Design
JF - Crystal Growth & Design
IS - 3
ER -