1.Sodium mefenamate as a solution for the formulation and dissolution problems of mefenamic acid.
Bani-Jaber A1, Hamdan I, Al-Khalidi B. Chem Pharm Bull (Tokyo). 2007 Aug;55(8):1136-40.
Sodium salt formation of mefenamic acid (MA) was studied as a way to solve the formulation and dissolution problems of MA. For this purpose, sodium salt of mefenamic acid (Na-MA) was prepared by reacting MA powder with equimolar sodium hydroxide in an aqueous phase, and consequently, Na-MA solution was obtained. The resultant solution was lyophilized and Na-MA powder was collected. The salt formation was confirmed by the results of fourier transformation-infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) studies on Na-MA powder in comparison to MA powder. Na-MA powder was assessed for direct compressibility, in comparison to MA powder, when formulated as a mixture with minimum amount of Avicel((R)) pH 101 and then compressed into tablets using a hydraulic tablet press. Na-MA tablets exhibited satisfactory hardness and friability, and did not show capping or lamination. On the other hand, some MA tablets showed capping or lamination upon compression and all the tested MA tablets for friability capped.
2.Salicylate enables cochlear arachidonic-acid-sensitive NMDA receptor responses.
Ruel J1, Chabbert C, Nouvian R, Bendris R, Eybalin M, Leger CL, Bourien J, Mersel M, Puel JL. J Neurosci. 2008 Jul 16;28(29):7313-23. doi: 10.1523/JNEUROSCI.5335-07.2008.
Currently, many millions of people treated for various ailments receive high doses of salicylate. Consequently, understanding the mechanisms by which salicylate induces tinnitus is an important issue for the research community. Behavioral testing in rats have shown that tinnitus induced by salicylate or mefenamate (both cyclooxygenase blockers) are mediated by cochlear NMDA receptors. Here we report that the synapses between the sensory inner hair cells and the dendrites of the cochlear spiral ganglion neurons express NMDA receptors. Patch-clamp recordings and two-photon calcium imaging demonstrated that salicylate and arachidonate (a substrate of cyclooxygenase) enabled the calcium flux and the neural excitatory effects of NMDA on cochlear spiral ganglion neurons. Salicylate also increased the arachidonate content of the whole cochlea in vivo. Single-unit recordings of auditory nerve fibers in adult guinea pig confirmed the neural excitatory effect of salicylate and the blockade of this effect by NMDA antagonist.
3.General trends in the desolvation behavior of calcium salts.
Atassi F1, Byrn SR. Pharm Res. 2006 Oct;23(10):2405-12. Epub 2006 Aug 23.
PURPOSE: This paper is concerned with the solid-state characterization of dehydrated calcium salts as well as the effect of dehydration on the physical properties of these salts.
4.Biological evaluation of bismuth non-steroidal anti-inflammatory drugs (BiNSAIDs): stability, toxicity and uptake in HCT-8 colon cancer cells.
Hawksworth EL1, Andrews PC2, Lie W1, Lai B3, Dillon CT4. J Inorg Biochem. 2014 Jun;135:28-39. doi: 10.1016/j.jinorgbio.2014.02.012. Epub 2014 Mar 1.
Recent studies showed that the metal-coordinated non-steroidal anti-inflammatory drug (NSAID), copper indomethacin, reduced aberrant crypt formation in the rodent colon cancer model, while also exhibiting gastrointestinal sparing properties. In the present study, the stability and biological activity of three BiNSAIDs of the general formula [Bi(L)3]n, where L=diflunisal (difl), mefenamate (mef) or tolfenamate (tolf) were examined. NMR spectroscopy of high concentrations of BiNSAIDs (24h in cell medium, 37°C) indicated that their structural stability and interactions with cell medium components were NSAID specific. Assessment of cell viability using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium]bromide (MTT) assay showed that the toxicity ranking of the BiNSAIDs paralleled those of the respective free NSAIDs: diflH<mefH<tolfH. While the IC50 values of the BiNSAIDs (ranging between 16 and 81μM) were lower than the free NSAIDs, it was apparent that the toxicity of the BiNSAIDs was due to the molar ratio of the three NSAID molecules contained in the BiNSAIDs, with the exception of [Bi(difl)3].