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Effect of Deep Eutectic System (DES) on Oral Bioavailability of Celecoxib: In Silico, In Vitro, and In Vivo Study. | LitMetric

AI Article Synopsis

  • Different deep eutectic systems (DES) were created using choline chloride in combination with various substances like urea, glycerol, malonic acid, and ascorbic acid, and characterized using light microscopy and infrared spectroscopy.
  • Among these, the CC-malonic acid system significantly improved the solubility of the drug celecoxib, showing a 10,000-fold increase compared to deionized water, which facilitated further study of the drug within this system.
  • In vivo studies indicated that the DES-based delivery system enhanced drug absorption and bioavailability, suggesting its potential for improving the effectiveness of drugs with low solubility.

Article Abstract

Different deep eutectic systems (DES) of choline chloride (CC)-urea (UA) (1:2), CC-glycerol (GLY) (1:2), CC-malonic acid (MA) (1:1), and CC-ascorbic acid (AA) (2:1) were generated and characterized by polarized light microscope (PLM) and Fourier transform infrared spectroscope (FTIR). The equilibrium solubility of celecoxib (CLX) in DES was compared to that in deionized water. The CC-MA (1:1) system provided ~10,000 times improvement in the solubility of CLX (13,114.75 µg/g) and was used for the generation of the CLX-DES system. The latter was characterized by PLM and FTIR to study the microstructure and intermolecular interaction between the CLX and CC-MA (1:1) DES. FTIR demonstrated the retention of the chemical structure of CLX. In vitro drug release studies in FaSSIF initially demonstrated high supersaturation, which decreased by ~2 fold after 2 h. Density functional theory (DFT)-based calculations provided a molecular-level understanding of enhanced solubility. Gibbs free energy calculations established the role of the strongest binding of CLX with CC and MA. A phase solubility study highlighted the role of hydrotropy-induced solubilization of the CLX-DES system. Animal pharmacokinetic studies established 2.76 times improvement in C, 1.52 times reduction in t, and 1.81 times improvement in AUC. The overall results demonstrated the potential of developing a DES-based supersaturating drug-delivery system for pharmaceutical loading of drugs having solubility and dissolution rate-limited oral bioavailability.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10534828PMC
http://dx.doi.org/10.3390/pharmaceutics15092351DOI Listing

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