Particle engineering/different film approaches for earlier absorption of meloxicam

Meloxicam (Mel) is a non-steroidal potent anti-inflammatory drug with effective analgesic effect for various situations; e.g. postoperative pain. The early systemic exposure to Mel and hence the rapid onset of pharmacological action is limited by its poor water solubility; a situation which may be more pronounced during acute pain episode because of reduced gastric motility that affects disintegration and dissolution of solid dosage forms. To overcome delayed absorption of Mel, improvement in the dissolution behavior of Mel is essential. Firstly, Mel spherical crystalline agglomerates (SCA) were prepared. Secondly, selected Mel SCA were integrated into intraoral fast disintegrating (OF) and edible (EF) films, they possess larger surface area that leads to rapid disintegration and release of the drug into the oral cavity within seconds and hence a rapid onset of action could be achieved. Stability study of formulations resulting in faster and higher extent of dissolution and suitable mechanical properties (G3 and G12) revealed their physical and chemical stability after three months of storage under different conditions. Both G3 and G12 successfully offered rapid absorption rate and accordingly an earlier systemic exposure to Mel compared to Mobic tablets as revealed by significantly earlier T _max and higher AUC_0–0.5h and AUC_0–4h. T _max following G3 fast disintegrating film administration was comparable to that reported following Mel parenteral administration but avoiding patient inconvenience. Both films may be suitable alternative to conventional oral and intramuscular Mel especially when earlier onset of action is required (in acute conditions).     

美洛昔康口腔崩解片中美洛昔康含量测定方法研 究简

目的 建立测定美洛昔康口腔崩解片中美洛昔康含量的反相高效液相色谱法.方法 色谱柱为KromasilC18柱（250 mm×4.6mm,5 μm）,流动相为0.1 mol/L醋酸铵溶液-甲醇（50：50）,柱温为室温,流速为1.0 mL/min,检测波长为271 nm.结果 美洛昔康质量浓度在40 ～ 60 μg/mL范围内与峰面积呈良好线性关系（r=0.999 8）,平均回收率为100.45％,RSD为0.55％（n=9）.结论 该方法简便、灵敏、准确、专属性强、重现性好,为产品的质量标准研究提供了理论依据.     

活血化瘀法联合来氟米特片、美洛昔康分散片治疗类风湿关节炎临床疗效观察

目的：通过观察活血化瘀法联合来氟米特片、美洛昔康分散片治疗类风湿关节炎的临床疗效,探讨中西医结合治疗类风湿关节炎的优势。方法：对确诊的159例患者随机分为两组,对照组服用来氟米特片和美洛昔康分散片治疗,治疗组在此基础上加服自拟活血化瘀中药方剂治疗。两组均连续服用3个月为1个疗程,1个疗程后观察并统计疗效。结果：治疗组总有效率为87.5%,显著高于对照组的74.68%。治疗组治疗后RF、ESR、补体C3等指标改善程度明显,统计学有显著性差异（P〈0.05）。结论：活血化瘀法联合来氟米特片、美洛昔康分散片治疗类风湿关节炎疗效较好,且较单纯西医治疗效果显著。     

美洛昔康对老年痴呆模型大鼠学习记忆能力及脑组织SOD，MAO-B，MDA的影响

目的探讨美洛昔康对老年痴呆模型大鼠抗痴呆作用及其作用机制。方法采用慢性铝过负荷建立大鼠脑损伤老年痴呆动物模型,通过每天给予大鼠灌胃葡萄糖酸铝（Al3＋200 mg.kg-1）溶液,每周持续5 d,连续灌胃20周建立老年痴呆大鼠动物模型;根据大鼠体重每千克给予3mg或1mg美洛昔康的比例,在大鼠灌胃给予铝后进行美洛昔康溶液灌胃。建模成功后,分别观察大鼠空间学习记忆能力、海马病理形态学变化及大鼠脑组织SOD,MAO-B活性和MDA含量。结果老年痴呆模型大鼠学习记忆能力明显下降、海马神经元损伤,而在大鼠脑组织中MDA含量及MAO-B活性则呈现明显升高趋势,同时大鼠脑组织SOD活性则显著降低。给予美洛昔康能明显改善老年痴呆模型大鼠的学习记忆能力,减轻大鼠海马神经元细胞损伤,同时使老年痴呆大鼠脑组织MDA含量明显减少,而大鼠脑组织MAO-B活性升高及SOD活性降低的趋势得到明显遏制。结论美洛昔康使老年痴呆模型大鼠学习记忆能力有明显的改善,对老年痴呆模型大鼠有显著的保护作用。     

Specific COX-2 inhibitor, meloxicam, suppresses proliferation and induces apoptosis in human HepG2 hepatocellular carcinoma cells

BACKGROUND AND AIMS: Cyclooxygenase-2 (COX-2) is associated with carcinogenesis. The aim of this study was to investigate the expression of COX-2 in four hepatocellular carcinoma (HCC) cell lines, and evaluate the effect of a selective COX-2 inhibitor, meloxicam, in HepG2, a high COX-2 expressing cell line. METHODS: Expression of COX-2 was detected using RT-PCR, Western blotting and immunohistochemical analysis. Cell proliferation was measured using MTT assay. Cell cycle distribution was determined by flow cytometry. Apoptosis was detected with TUNEL method. Expression of proliferating cell nuclear antigen (PCNA), cell cycle regulatory proteins including cyclins A, B1, D1 and E, and apoptosis-related proteins including Fas, Fas ligand and Bcl-2 were examined using Western blotting. RESULTS: Cyclooxygenase-2 was intensely expressed in HepG2, HLE and BEL7402 cells, but weakly expressed in SMMC-7402 cells. Meloxicam suppressed proliferation of HepG2 cells in a dose- and time-dependent manner, resulting in cell cycle arrest in S phase and cell accumulation in G0/G1 phase. Expression of PCNA, cyclin A but not cyclin B1, cyclin D1 or cyclin E was down-regulated by meloxicam. Meloxicam also induced apoptosis of HepG2 cells, with increased expression of Fas ligand, but the expression of Fas and Bcl-2 was not affected by meloxicam treatment. CONCLUSIONS: The present study demonstrates that the specific COX-2 inhibitor meloxicam suppresses proliferation and induces apoptosis in HCC cells that express COX-2, suggesting that COX-2 inhibition may offer a novel chemopreventive and therapeutic approach for HCC.     

膝关节镜术后关节腔内注射芬太尼和口服美洛昔康的镇痛效果比较

目的：研究膝关节镜术后关节腔内注射芬太尼和口服非甾体类药物（NSAIDs）美洛昔康的镇痛效果。方法：选取择期行膝关节镜手术患者180例,随机分为3组,每组60例,A组术后关节腔内注入芬太尼,并在术后给予美洛昔康口服;B组术后关节腔内注入芬太尼;C组术后给予美洛昔康口服。分别在术后2、8、24、48、72h,以VAS评估患者术后的疼痛水平。结果：2hA组较B组的评分差异无显著性意义。2h后A组评分较B组更低（P〈0.05）,A组和B组较C组的评分明显降低（P〈0.05）。结论：芬太尼与美洛昔康联合使用可以有效缓解膝关节镜术后疼痛,镇痛效果优于单独使用;芬太尼较美洛昔康效果更佳。     

美洛昔康和萘丁美酮双盲对照治疗骨关节炎的比较

目的 :比较美洛昔康和萘丁美酮治疗骨关节炎的疗效和安全性。方法 :为随机、双盲、多中心、平行对照研究。共完成病例 60例 ,美洛昔康组 31例 (男性 3例 ,女性 2 8例 ,年龄 5 4a±s 8a) ,用美洛昔康 7.5mg ,qd ;萘丁美酮组 2 9例 (男性 5例 ,女性 2 4例 ,年龄 5 5a± 7a) ,用萘丁美酮 10 0 0mg ,qd ,均在晚餐后口服给药 ,疗程 4wk。结果 :美洛昔康组总有效率为 89% ;萘丁美酮组为 83% (P >0 .0 5 )。不良反应发生率 ,美洛昔康组为 13% ;萘丁美酮组为 10 % (P >0 .0 5 ) ,以胃肠道反应为主。结论 :美洛昔康对骨关节炎具有明显抗炎镇痛作用 ,其疗效和安全性与萘丁美酮相似     

美洛昔康血药浓度的HPLC测定及其分散片的相对生物利用度

建立了人血浆中美洛昔康的 HPL C测定法 ,以测定其分散片的相对生物利用度。血样经盐酸酸化后以乙醚提取 ,进行 HPL C分析 ,色谱柱为 Hypersil ODS2 (2 5 0× 4.6 m m,5 μm) ,流动相为甲醇 -水 -三乙胺 -冰醋酸 (2 5 0 0∶15 0 0∶ 15∶ 7)检测波长为 35 5 nm,尼美舒利为内标。结果表明在 0 .0 3～ 8.0 μg/ ml范围内峰面积与浓度线性关系良好 (r=0 .9999) ,最低检出浓度为 2 .5 ng/ ml,回收率为 93.6 %～ 97.7%。 2 0名健康受试者随机交叉口服国产和进口美洛昔康分散片后 ,其体内过程符合一室模型 ,统计学结果表明两种制剂生物等效     

Pharmacokinetic studies of meloxicam following oral and transdermal administration in Beagle dogs

Aim： The potential for topical delivery of meloxicam was investigated by examining its pharmacokinetic profiles in plasma and synovial fluid following oral and transdermal administration in Beagle dogs.
Methods： The experiment was a two-period, crossover design using 6 Beagle dogs. Meloxicam tablets were administered orally at a dose of 0.31 mg/kg, and meloxicam gel was administered transdermally at a dose of 1.25 mg/kg. Drug concentrations in plasma and synovial fluid were determined by liquid chromatography-tandem mass spectrometry （LC/MS/MS）. The pharmacokinetic parameters were calculated using the Topfit 2.0 program. Results： The pharmacokinetic results showed that AUC0-t （23.9±8.26 pg·h·mL^-1） in plasma after oral administration was significantly higher than after transdermal delivery （1.00±0.43 pg·h·mL^-1）. In contrast, the ratio of the average concentration in synovial fluid to that in plasma following transdermal administration was higher than that for an oral delivery. The synovial fluid concentration in the treated leg was much higher than that in the untreated leg, whereas the synovial fluid concentration in the untreated leg was similar to the plasma concentration.
Conclusion： The high concentration ratio of synovial fluid to plasma indicates direct penetration of meloxicam following topical administration to the target tissue. This finding is further supported by the differences observed in meloxicam concentrations in synovial fluid in the treated and untreated joints at the same time point. Our results suggest that transdermal delivery of meloxicam is a promising method for decreasing its adverse systemic effects.