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Aims: To optimize, formulate, and evaluate a Nanostructured Lipid Carrier (NLC) based transdermal gel of Etodolac (ETD). Objective: To avoid issues of conventional route ETD administration like first pass metabolism, gastric ulceration, hemorrhage, and being a class-II drug with less solubility. A transdermal gel of nanostructured lipid carrier for ETD has been developed. Formulation will execute faster onset of action, increased penetration, permeation with extended release of the drug for a longer duration. Methods: A central composite 32 factorial design is used to plan experiments. NLCs are prepared by the method of melt emulsification and ultrasonication. Compritol 888ATO and Miglyol are used as solid and liquid lipid phases. Surfactant Pluronic F68 showed a significant effect on particle size, entrapment efficiency, and drug release. Particle size characterized using photon correlation spectroscopy and scanning electron microscopy. Cumulative drug release studied using an artificial diffusion cell and a dialysis membrane. A skin permeation study was performed using goat skin at 32°C ± 0.5°C. The efficacy of the NLC gel was verified using a pharmacodynamic study followed by stability study for 3 and 6 months. Results: The optimized batch of ETD NLC found spherical with a 241.3 nm particle size with 0.392 PDI,-29 mV zeta potential. Entrapment efficiency and cumulative drug release were found to be 64.21 ± 1.23% and 70.12 ± 2.10% (after 12 hours), respectively. All batches followed zeroorder drug release kinetics and non-Fickian (Super Case II transport) with 0.1619 mg/cm2/hr transdermal flux. The NLC gel of ETD showed a quick onset and lengthened therapeutic activity until 24 hours compared to the micellar ETD gel. Conclusion: Etodolac NLC batch successfully optimized using central composite design. The relationships between the components of the NLC-total lipid:drug and surfactant-and the outcomes- particle size,%entrapment and% drug release-were better understood by examining several contour plots. The results of the experimental and predicted formulations were found to be in good agreement with slight bias, demonstrating the reliability of the optimization process.

The inflammatory mechanisms are complex due to the involvement of multiple pathways. The messengers like PIP2 and IP3 are phosphonate containing biomolecules which are desirable for the delivery of biological responses. In the present study, we designed a novel series of nitrogen and non-nitrogen containing bisphosphonates fused with more lipophilic chalcone moiety. We assume to maintain the hydrophilic ratio of BPs with hydrophobic chalcone substitution. The synthesized compounds 1–11, demonstrated potential anti-inflammatory activity against carrageenan-induced rat paw edema model and in-vitro COX-2 assay. The modifications over the synthesized derivatives were supported by in silico studies and SAR of bisphosphonates. In vitro study was carried out at concentration of 1µM while in vivo study was performed using the carrageenan-induced rat paw edema model. From the study it was concluded that the binding pattern of synthesized derivatives was remarkably similar to the co-crystallized ligand, and also the anti-inflammatory effect of compound was based on the interactions between bisphosphonates and amino acids. The distance between the P-C-P linkage of bisphosphonates to nitrogen and free carbon attached to nitrogen were found to be important for the maximum interaction and biological response considering the co-crystalized ligand in another enzyme. An assessment of cyclooxygenase inhibitory activity (in vitro) of compounds (1, 9, and 11) revealed a structure activity relationship while in vivo inhibitory action of compound 9, 11, 1, 10, and 3 is indicative of its inhibitory action on the prostaglandin synthesis which may be mediated through the inhibition of COX-2 enzyme.

Lafutidine (LTD) is a histamine H2 receptor antagonist, with anti-ulcer and mucosal protective activity. A sensitive and selective stability-indicating reversed- phase high -performance thin-layer chromatography (RP-HPTLC)/Densitometry method is suggested for the determination of LTD in the presence of its acid, alkaline, oxidative and dry heat degradation products. Stress testing of LTD was done according to the International Conference on Harmonization (ICH) guidelines in order to validate the stability-indicating power of the analytical procedures. Stress testing demonstrated that LTD underwent acid, alkaline, oxidative and dry heat degradation; on the other hand, it showed stability towards neutral and photo degradation. Chromatography was performed on aluminum-backed silica gel 60 RP-18 F254 S plates with Methanol: Water: Triethylamine 8: 2: 0.5 (v/v) as mobile phase. Densitometric scanning was performed at 276 nm. The system gave compact bands for LTD (Rf 0.67 ? 0.02). Linear regression analysis data for the calibration plots discovered a good linear relationship with r2 > 0.99 in the working concentration range 500 to 3000 ng per band. The limits of detection and quantification were 23.51 ng and 71.26 ng, respectively. The developed method can routinely be used for analysis of LTD in bulk and pharmaceutical formulations.