Naproxen

A rapid, simple, selective, and specific reverse phase high performance liquid chromatography (RP-HPLC) method was developed and validated for estimation of Naproxen and Sumatriptan from tablet using spiked human plasma. The chromatographic separation was performed on Phenomenex Luna C18 column (5μm, 25cmx4.6mm id)  with a mobile phase comprised of Acetonitrile: Methanol: phosphate buffer pH 6 (50:10:40 v/v), at a flow rate of 1.0ml/min. The calibration curve was linear in the range of 1-3 µg/ml. The developed method was found to accurate and sensitive. Results of recovery studies prove the extraction efficiency. Stability data indicated that Sumatriptan and Naproxen was stable in plasma after three freeze thaw cycles and upon storage at −20°C for 30 days.

A series of pyridinamide-containing naproxen derivatives were synthesized through different routes starting with naproxenoyl chloride (2) which, upon reaction with 2-or 3-aminopyridine, gave the corresponding naproxenamide derivatives 3a,b. Also, urea derivatives 5a,b were obtained through the reaction of compound 2 with sodium azide followed by reaction with 2-or 3-aminopyridene via Curtius rearrangement. In addition, naproxenoyl isothiocyanate was synthesized and reacted with 2- or 3-aminopyridine, where the thiourea derivatives 7a,b were obtained. Furthermore, cyanoacetanilide 9 was synthesized and reacted with acetylacetone, arylidenemalononitriles or arylidenecyanoacetate to furnish the corresponding pyridine amide derivatives 10-13. All compounds were screened for anti-inflammatory activity using an in vivo rat paw edema model, from which six of them exhibited higher potency than naproxen. The ulcerogenic effect of most of the active compounds was also screened. In ulcerogenicity screening, the potent anti-inflammatory compounds 3b, 5a and 5b were devoid of any ulcerative effect. This is contrary to naproxen which caused 100% ulcerative effect on all tested animals. Structure-based molecular modeling described that the virtual screening agrees with the SAR of in vivo anti-inflammatory and ulcerogenic activities. Furthermore, all the synthesized compounds were screened for their anti-microbial activity.

Naproxen is a non-steroidal anti-inflammatory drug (NSAID) commonly used for the reduction of mild to moderate pain, fever, inflammation and stiffness caused by conditions such as osteoarthritis, rheumatoid arthritis, psoriatic arthritis, gout, ankylosing spondylitis, injury, menstrual cramps, tenditis, bursitis and the treatment of primary dysmenorrheal. The reason behind incorporation of Naproxen in Niosomes as this non-ionic surfactants vesicles offer several advantages over other drug carriers like liposome with respect to its biocompatibility, simple and controllable preparation, their capacity to carry large amount of drug, commercially availability, capable of entrapping hydrophilic and hydrophobic drug, cheaper in cost, any special condition not require for the use of the surfactant. The niosome system which achieves the site specific delivery of drug with controlled release kinetics of drug in predictable manner. Before this preparation, prior preparations had been made known as Pro-niosomes with Cholesterol, Surfactant, and Ethanol which later on converting to Niosomes.