Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) - Volume 23, Issue 3, 2024

Emulgel dosage form is an advanced form of transdermal drug delivery. It is a combination of emulsion and gel in a definite ratio. Emulsions are incorporated into the gel with proper mixing. The emulsion present in emulgel can be either oil/water or water/oil, which is thickened by mixing it with a gelling agent.

On the basis of the solubility of lornoxicam in various oils, a surfactant and a co-surfactant were selected for further research. For the preparation of emulgel, the emulsion was prepared with Smix (surfactant and co-surfactant) in a ratio of 1:2. The prepared emulsion was incorporated into different concentrations of carbapol 934 in a 1:1 ratio to make a homogenous emulgel.

The emulgel was inspected visually to see if it had any phase behaviour, spreadability, or grittiness by applying it to a slide. All formulations were evaluated for pH, physical properties, drug content, spreadability, extrudability, swelling index, viscosity, and centrifugation. Franz diffusion cell was used to perform in-vitro release of formulation with the help of egg membrane. Among all formulations, F3 showed 83% release after 6 hours and showed acceptable physical properties like homogeneity, colour, consistency, pH value, spreadability, extrudability, and drug content.

Thus, emulgel can be regarded as a more feasible drug delivery system for hydrophobic drugs (lornoxicam) than the currently marketed formulation. Optimized emulgel formulation consists of a microemulsion of lornoxicam, 1% of carbopol 934, propylene glycol, sodium benzoate, lemon grass oil, glycerin, and distilled water. In the in-vitro release studies, pH 7.4 phosphate buffer emulgel formulation (F3) showed 83% after 6 hours. Emulgel was found to be stable under stable conditions.

The emulgel of the poorly water-soluble drug (lornoxicam) was formulated. The components and their optimum ratio for the formulation of microemulsion were obtained by solubility studies and droplet size analysis. Thus, microemulsion can be regarded as a more feasible dose delivery system for lornoxicam than the currently marketed tablet, capsule, and injection formulations. Optimized microemulsion of lornoxicam was incorporated into the gel base. Therefore, it may be concluded that emulgel of lornoxicam can be used as a controlled-release dosage form of the drug for local application in rheumatoid arthritis.

Non-communicable diseases are chronic systemic inflammation in humans that occurs because of enhanced inflammatory mediators of the arachidonic acid cascade. We aimed to explore whether the lead chalcone compounds could exhibit anti-inflammatory activity via dual blockage of COX-2/5-LOX enzymes and their regulatory mechanism.

RAW 264.7 macrophages were collected from NCC, Pune, for in-vitro experiments. The IC50 values of chalcone compounds C45 and C64 were calculated. RAW 264.7 macrophages were treated with C45 and C64 (10%, 5%, 2.5%, 0.125%, and 0.0625% concentration). The cell viability was carried out with an MTT assay. The COX-1, COX-2, 5-LOX, PGE2, and LTB4 levels were detected by ELISA-based kits. The in-vivo evaluation was carried out in Male Wistar rats (250-300 g, 7-8 weeks old) with acute and chronic anti-inflammatory models and histopathological studies on the stomach, liver, and kidney.

The present study described the in-vitro and in-vivo biological evaluation of dual COX-2/5-LOX inhibitors in chalcone derivatives (C45 and C64) compounds showed the most effective COX-2 and 5-LOX inhibition with IC50 values 0.092 and 0.136 µM respectively. Simultaneously, compound C64 showed comparable selectivity towards COX-2 with a Selectivity Index (SI) of 68.43 compared to etoricoxib, with an SI of 89.32. In-vivo carrageenan-induced rat paw oedema activity, the compound C64 showed a significant reduction in oedema with 78.28% compared to indomethacin with 88.07% inhibition. Furthermore, cotton pellet-induced granuloma activity revealed that compound C64 significantly reduced 32.85% compared with standard 40.13% granuloma inhibition.

The chalcone compound C64, (E)-1-(4-Amino-2-hydroxyphenyl)-3-(3,4,5-trimethoxyphenyl)-prop-2-en-1-one was proved to be a potent and novel Dual COX-2/5-LOX inhibitor with improved gastric safety profiling.

This research aims to create a gel formulation of Brassica juncea leaf extract and assess its anti-inflammatory properties using an in silico study. The anti-inflammatory activity has been compared with Diclofenac molecules in PDB id: 4Z69. Further, the Absorption, Distribution, Metabolism, Excretion, and Toxicity analysis has been performed to ensure the therapeutic potential and safety of the drug development process. The Quality by Design tool has been applied to optimize formulation development.

The extracted gel is characterized by performing Fourier transformer infrared, zeta potential, particle size, Scanning Electron Microscope, and entrapment efficiency. Further, the formulation is evaluated by examining its viscosity, spreadability, and pH measurement. An In vitro study of all nine extract suspensions was conducted to determine the drug contents at 276 nm.

The optimized suspension has shown the maximum percentage of drug release (82%) in 10 hours of study. Animal study for anti-inflammatory activity was performed, and results of all five groups of animals compared the % inhibition of paw edema at three hours; gel (56.70%), standard (47.86%), and (39.72%) were found.

The research could conclude that the anti-inflammatory activity of gel formulation is high compared to extract, and a molecular docking study validates the anti-inflammatory therapeutic effects. ADMET analysis ensures the therapeutic effects and their safety.