Issue 39, 2020

Exploring the novel green eutectic solvent for the synthesis of 4-hydroxy-2-methyl-N-2-pyridinyl-2H-1,2,-benzothiazine-3-carboxamide 1,1-dioxide with benzoic acid cocrystal using a co-grinding technique

Abstract

In the present study, the suitability of a green eutectic solvent, a mixture of menthol and camphor for cocrystal synthesis has been investigated to improve the biopharmaceutical properties of poorly water-soluble drugs. To explore this, piroxicam (PRX) (4-hydroxyl-2-methyl-N-2-pyridinyl-2H-1,2,-benzothiazine-3-carboxamide 1,1-dioxide), a non-steroidal anti-inflammatory drug was taken as a model drug and benzoic acid (BA) used as a co-former. An equimolar proportion of PRX and BA was ground in a mortar pestle with dropwise addition of the green eutectic solvent, and the ground solids were then dried and characterized to confirm the formation of the PRX–BA cocrystal. Powder X-ray diffraction and differential scanning calorimetry showed the potential formation of the cocrystal from the appearance of new peaks in the diffraction pattern and a change in thermal behavior, respectively. Fourier transform infrared spectroscopy revealed the formation of C–H⋯O and C–H⋯N hydrogen bonds between the OH or NH group of PRX with the carbonyl group of BA at the ratio of 1 : 1. PRX–BA cocrystals showed a 3-fold increase in the solubility, and an intrinsic dissolution rate with 15-fold improvement in the oral bioavailability in rats compared to the pure PRX. Thus, the green eutectic solvent-based grinding technology is a selective single step method for the continuous manufacturing of the cocrystal that can serve as an alternative to traditional methods of cocrystal synthesis.

Graphical abstract: Exploring the novel green eutectic solvent for the synthesis of 4-hydroxy-2-methyl-N-2-pyridinyl-2H-1,2,-benzothiazine-3-carboxamide 1,1-dioxide with benzoic acid cocrystal using a co-grinding technique

Article information

Article type
Paper
Submitted
15 Jul 2020
Accepted
09 Sep 2020
First published
11 Sep 2020

New J. Chem., 2020,44, 17088-17098

Exploring the novel green eutectic solvent for the synthesis of 4-hydroxy-2-methyl-N-2-pyridinyl-2H-1,2,-benzothiazine-3-carboxamide 1,1-dioxide with benzoic acid cocrystal using a co-grinding technique

R. Solaimalai, G. Shinde, A. Dharamsi and C. Kokare, New J. Chem., 2020, 44, 17088 DOI: 10.1039/D0NJ03570J

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