Abstract
BackgroundCocrystallization is one of the crystal engineering strategies used to alter the physicochemical properties of drugs that are poorly water-soluble. Gliclazide (GLZ), an antidiabetic drug, belongs to Biopharmaceutical Classification System class-II (low solubility and high permeability) and has low bioavailability, resulting in poor therapeutic effects in patients. Therefore, to impart better solubility and bioavailability of GLZ, the study was carried out by preparing GLZ cocrystals using liquid-assisted grinding method with three coformers [3,5-dinitrosalicylic acid (DNS), 2,6-pyridine dicarboxylic acid (PDA), and L-proline (LPN)], and these were characterized using Differential Scanning Colorimetry (DSC), Powder X-ray diffraction (PXRD), Fourier Transform Infra-red spectroscopy (FTIR), and Raman spectral studies. Further, Scanning electron microscopy (SEM) analysis, accelerated stability, solubility, in vitro dissolution studies, and in vivo pharmacokinetic studies were performed in male Wistar rats.ResultsDSC and PXRD analysis confirmed the formation of the GLZ cocrystals. Hydrogen bonding between pure GLZ and its coformers was demonstrated based on FTIR and Raman analysis. SEM data showed morphological images for GLZ cocrystals differed from those of pure GLZ. In comparison with pure GLZ, these GLZ cocrystals have greatly improved solubility, in vitro dissolution, and in vivo profiles. Among the three, GLZ–DNS cocrystals outperformed the pure drug in terms of solubility (6.3 times), degradation (1.5 times), and relative bioavailability (1.8 times).ConclusionHence, cocrystallization of GLZ leads to improved physicochemical properties of poorly soluble drug gliclazide.
Highlights
Cocrystallization is one of the crystal engineering strategies used to alter the physicochemical properties of drugs that are poorly water-soluble
In continuation of our attempts to improve the solubility of poorly soluble yet biologically significant drugs, using cocrystallization as a suitable technique [27, 28], we focused our attention on gliclazide (GLZ) (Fig. 1)
The potential functional groups which are essential for the non-covalent interactions between molecules of GLZ and coformers were NH of GLZ, COOH and OH moieties of DNS, and COOH groups of LPN and pyridine dicarboxylic acid (PDA)
Summary
Cocrystallization is one of the crystal engineering strategies used to alter the physicochemical properties of drugs that are poorly water-soluble. Drug discovery is a dynamic process resulting in a diverse set of new molecules as new chemical entities (NCE). Developing these NCEs as suitable drugs into. Eesam et al Future Journal of Pharmaceutical Sciences (2021) 7:124 of these techniques depends on the specific physicochemical nature of the molecule in question. Some of these techniques suffer from inherent problems, viz. Crystal engineering through cocrystallization is a potential approach to address the problems associated with these poorly soluble drug candidates. Some more like Steglatro [25], and TAK-20 [26], Co-crystal E-58425 [26] are under different phases of clinical development
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
