Spectroscopic studies of microenvironment dictated structural forms of piroxicam and meloxicam

Long acting non-steroidal anti-inflammatory drugs (NSAIDs) belonging to the oxicam group have attracted special interest because of their diverse biological functions. In this study we present the influence of microenvironment on the spectral properties of two oxicam drugs viz. piroxicam and meloxicam. For the two drugs, a high energy shift of the UV absorption maxima was observed with increasing drug concentrations both in protic solvent like ethanol and aprotic solvent like dimethyl sulfoxide (DMSO). Studies involving variation of percentage volume of water as well as pH, using absorption and steady state fluorescence spectroscopy, allow us to identify the principal species present at different concentrations of the drugs. It is found that even trace quantity of water present in the solvent becomes significant at low concentration of the drug making the water/drug ratio sufficiently large to support the formation of anion. As the concentration of the drug increases, the number of water molecules available per drug molecule decreases and most of the drug molecules face a relatively apolar environment in which zwitterionic/neutral species become predominant. This results in a concentration-dependent high-energy shift of the absorption maximum. This study demonstrates how microenvironments of these drugs guide the nature of the predominant form present in solution.     

美洛昔康的合成

从糖精钠出发,经４步反应合成美洛昔康,总收率４３．５％,首次分离,纯化了甲基化反应的重要副产物,经元素分析、氢谱,质谱确定为双甲基化产物。用重结晶方法对单甲基化物进行纯化。     

Determination of Meloxicam in Tablet Formulations by Ultraviolet Spectrophotometry and High-Performance Liquid Chromatography

ABSTRACT

Assay procedures based on UV spectrophotometry and high-performance liquid chromatography (HPLC) have been developed for the determination of meloxicam in tablet formulations. The HPLC method used a reversed-phase C18 column with 0.05M Tris acetic acid buffer - tetrabutylammonium reagent–acetonitrile as eluent, and UV detection at 360nm with isoxicam as the internal standard. The UV method was based on measuring an acidic solution of the drug at 341nm. A comparison was established in terms of linearity, sensitivity, precision, and accuracy. Both methods were simple and rapid. HPLC was more precise and more accurate, the UV technique was slightly faster.     

The interactions of metal ions with nonsteroidal anti-inflammatory drugs (oxicams)

Much work has been focused on interactions of metal ions with nonsteroidal anti-inflammatory drugs (oxicams). Numerous attempts to synthesize several metal complexes have been published. This review highlights the synthesis and properties of the synthesized metal complexes. Different physico-chemical methods (IR, UV–Vis, measurement, thermal analysis, and NMR spectroscopy) as well as the bioactivity of the metal compounds are mentioned.     

Physical characterization of meloxicam-β-cyclodextrin inclusion complex pellets prepared by a fluid-bed coating method

Meloxicam-β-cyclodextrin (ME-β-CD) inclusion complex was prepared by a fluid-bed coating technique upon solvent removal and simultaneous depositing onto the surface of nonpareil pellets and using PVP K30 as a binding agent to facilitate good coating. The resultant pellets were spherical and intact in shape with good flowability and friability. SEM analysis showed that the pellets were smooth and had a tightly coated inclusion complex layer. In vitro dissolution of the inclusion complex pellets in pH 7.4 pho...     

美洛昔康-Cu(Ⅱ)-牛血清白蛋白三元配合物的荧光光谱法研究

应用荧光光谱法研究了生理条件下美洛昔康对牛血清白蛋白,Cu(Ⅱ)对牛血清白蛋白以及Cu(Ⅱ)对美洛昔康和牛血清白蛋白荧光光谱特性的影响.结果表明:Cu(Ⅱ)和美洛昔康均可使牛血清白蛋白的荧光强度发生静态猝灭,并且在Cu(Ⅱ)存在下,美洛昔康对牛血清白蛋白的荧光猝灭作用显著增强.根据荧光猝灭双倒数图计算美洛昔康和牛血清白蛋白的结合常数为1.91×10~5,结合位点数为0.95;Cu(Ⅱ)与牛血清白蛋白之间的结合常数为1.70×10~4,结合位点数为0.78.     

Physical characterization of meloxicam-β-cyclodextrin inclusion complex pellets prepared by a fluid-bed coating method

Meloxicam-β-cyclodextrin （ME-β-CD） inclusion complex was prepared by a fluid-bed coating technique upon solvent removal and simultaneous depositing onto the surface of nonpareil pellets and using PVP K30 as a binding agent to facilitate good coating. The resultant pellets were spherical and intact in shape with good flowability and friability. SEM analysis showed that the pellets were smooth and had a tightly coated inclusion complex layer. In vitro dissolution of the inclusion complex pellets in pH 7.4 phosphate buffer was dramatically enhanced at an ME/CD ratio of 1/1. DSC and powder X-ray diffractometry proved the absence of crystallinity in the ME/CD inclusion complexes. Moreover, Fourier transform-infrared spectrometry together with Raman spectrometry indicated that the thiazole ring of ME was possibly included in the cavity of β-CD.     

Analysis of meloxicam by high-performance liquid chromatography with cloud-point extraction

A simple cloud-point extraction method for the determination of meloxicam in human serum was developed. Meloxicam was extracted from serum sample after adding 1 mL of 3% (v/v) Triton X-114 aqueous solution in the presence of 1M HCl and 60 mg NaCl. The meloxicam, present in the surfactant-rich phase, was enriched again with acetonitrile. Tenoxicam was used as the external standard. The separation was achieved on a C18 analytical column with a mobile phase consisting of aqueous acetic acid (1%, v/v) and acetonitrile (54:46, v/v). UV detection was performed at 360 nm. The response was linear over the range 45–2000 ng mL⁻¹ in human serum, and intra- and interday precisions of less than 15.0% were obtained. The relative error was within ±3.0%. The recoveries of meloxicam were larger than 92.0%. The method was compared with liquid–liquid extraction. The results showed that the new method has a considerable LOQ and higher recoveries but poorer precision than liquid–liquid extraction, which exhibited poor recoveries of less than 86.0%, precisions of less than 5.0% and relative errors of less than 7.0%. The method was used for the determination of meloxicam in healthy human volunteers.     

美洛昔康示差脉冲伏安法测定蛋白质的研究

在pH 4.8的NaAc-HAc缓冲液中,美洛昔康与蛋白质能够相互作用形成超分子复合物,使美洛昔康在0.584V处的氧化峰电流下降,在最佳条件下,峰电流的下降值同牛血清白蛋白(BSA)的浓度在2.0×10-8-6.0×10-7mol/L范围内呈线性关系,相关系数为0.9980,检出限为1.2×10-8mol/L,可应用于血清样品的测定.