Background:
The present study reports the formation of a cocrystal of candesartan with the
coformer methyl paraben, its characterization and determination of its bioavailability. Candesartan is a
poorly water-soluble drug having an anti-hypertensive activity. The recent patents on the cocrystals of the
drugs Progesterone (US9982007B2), Epalrestat (EP2326632B1), Gefitinib (WO2015170345A1), and
Valsartan (CN102702118B) for enhancement of solubility, helped in selection of the drug for this work.
Methods:
Candesartan cocrystal was prepared by solution crystallization method. The formation of a
new crystalline phase was characterized by Differential Scanning Calorimetry (DSC), Fourier Transform
Infrared (FTIR) and Powder X-ray Diffraction (PXRD) studies. Saturation solubility studies were
carried out in ethanol: water (50:50 % v/v) mixture. The dissolution studies were conducted in 900 ml
of phosphate buffer at pH 7.4(I.P.) with 0.7% w/w of Tween 20 at 50 rpm, maintained at a temperature
of 37±0.5°C in a USP type II dissolution apparatus. The pharmacokinetic behavior of candesartan and
its cocrystal was thereof investigated in male Wistar rats.
Results:
There was 6.94 fold enhancement in the solubility of candesartan after its cocrystallization.
The dissolution profile of the cocrystal exhibited significant improvement in solubility at 60 and 120
minutes and it remained stable in ethanol: water (50:50%v/v) mixture for 48 h as confirmed by PXRD
studies. The AUC0-24of the cocrystal was found to be increased by 2.9 fold in terms of bioavailability
as compared to the pure drug.
Conclusion:
The prepared cocrystal was found to be relatively more soluble than the pure drug and
also showed an enhanced oral bioavailability as compared to the pure drug.
Antimicrobial agents (AMAs) are widely exploited nowadays to meet the high demand for animal-derived food. It has a significant impact on the food chain whose end consumers are human beings. The burden of AMAs on humans comes from either meat or crops cultivated on soil containing high residual antibiotics, which are responsible for the global crisis of antibiotic resistance. Thus, the objective of this study was to design a selective and sensitive liquid chromatography−mass spectrometry (LC-MS)/MSbased simultaneous bioanalytical method for estimation of twenty AMAs in human plasma, raw meat, and soil samples. The selective extraction of all analytes from the above matrices was performed by the solid-phase extraction clean-up method to overcome the interferences. Analytes were separated on a Waters Symmetry Shield C18 (150 × 4.6 mm 2 , 5 μm) column, using an isocratic solvent system of methanol−0.5% formic acid (80:20, v/v) with 0.75 mL/min flow rate. The average extraction recoveries for all analytes in plasma were ranged from 42.0 to 94.0% with relative standard deviations (RSDs) below ±15%. All of the validation parameters are in accordance with the United State Food and Drug Administration (USFDA) guidelines. Moreover, the method was also valid for a broad plasma concentration range and can be proposed as an excellent method for routine pharmacokinetic studies, therapeutic drug monitoring, clinical analysis, and detection and quantitation of AMA remnants in raw meat as a standard quality control test for human consumption.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.