Please use this identifier to cite or link to this item: https://idr.l4.nitk.ac.in/jspui/handle/123456789/12843
Title: Salt/Cocrystal of Anti-Fibrinolytic Hemostatic Drug Tranexamic acid: Structural, DFT, and Stability Study of Salt/Cocrystal with GRAS Molecules
Authors: Nechipadappu, S.K.
Reddy, I.R.
Tarafder, K.
Trivedi, D.R.
Issue Date: 2019
Citation: Crystal Growth and Design, 2019, Vol.19, 1, pp.347-361
Abstract: Tranexamic acid (TXA) is an important and essential medicine needed in a health system and is approved by the US FDA for the treatment of excessive blood loss from trauma, postpartum bleeding, surgery, tooth removal, nosebleeds, and heavy menstruation. One of the notable disadvantages of the TXA drug is that has low absorption ( 35-40%) in the gastrointestinal tract, possibly due to its amphoteric nature. In the present work, nine molecular salts and two cocrystals of the TXA molecule have been synthesized by a simple water-mediated solvent evaporation method. The coformers/counterions used were salicylic acid (SAL), 3-hydroxybenzoic acid (3HBA), 2,4-dihydroxybenzoic acid (2,4HBA), 2,5-dihydroxybenzoic acid (2,5HBA), 2,6-dihydroxybenzoic acid (2,6HBA), gallic acid (GAA), oxalic acid (TXA), tartaric acid (TTA), fumaric acid (FUM), succinic acid (SUA), and crotonic acid (CRA). The synthesized salts/cocrystals were characterized by various spectroscopic, thermal, and XRD techniques. The crystal structures of all of the molecular adducts were determined by SC-XRD techniques. In the synthesized salts, charge-assisted acid amine heterosynthons and O-H O hydrogen bonds between the acid group of TXA and the coformer are favored, and the salts TXA-FUM and TXA-SUA were found to be isostructural on the basis of the isostructural parameters π and ? . In the cocrystal, molecules interacted through the acid group of the coformer with the carboxyl group of the TXA molecule. Further, these salts/cocrystals were found to be stable for a period of 6 months under ambient conditions ( 25-30 C, 60-65% RH). Furthermore, density functional theory (DFT) calculations were carried out to better understand the geometric structure of the molecules presented in our study. The interaction energies of the molecular salts and cocrystals were calculated, and they supported the reported structure of the crystalline adducts. The cocrystal formation in the case of TXA-GAA and TXA-CRA has been confirmed by a DFT calculation study, as the salt formation in these cases resulted in a higher interaction energy in comparison to the cocrystal. Consequently, these molecular salts offer promise for the development of new drug products of TXA, and a few salts, namely TXA-SAL and TXA-2,5HBA, offer the possibility of development of combination drugs. 2018 American Chemical Society.
URI: http://idr.nitk.ac.in/jspui/handle/123456789/12843
Appears in Collections:1. Journal Articles

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