布洛芬丁香酚酯前体药物的合成及其水解动力学

目的合成布洛芬丁香酚酯并研究其在不同pH水溶液中及血浆、肝匀浆中的水解动力学。方法以布洛芬和丁香酚为原料,经过酯化反应合成了布洛芬前体药物布洛芬丁香酚酯,利用HPLC法测定不同pH值的缓冲溶液、血浆及肝均浆中药物水解动力学。经UV、IR、MS和NMR确证了目标化合物的结构。结果布洛芬丁香酚酯在pH为1.10~9.96时水解速率常数不受pH影响,pH为10.91~11.91时随pH值增加水解速率增大;在血浆及肝均浆中布洛芬丁香酚酯可迅速水解成布洛芬和丁香酚。结论布洛芬丁香酚酯是一个具有良好前景的非甾体抗炎前体药物。     

单扫描示波极谱法测定布洛芬

目的 建立研究测定布洛芬的新方法。方法 应用单扫描示波极谱法。结果 在0．08mol／L HAc—NaAc（pH=4．2）支持电解质中，布洛芬在-1．06V处产生一极谱波，当氧化剂K2S2O8存在时，K2S2O8氧化布洛芬羰基还原中间体自由基，使布洛芬再生，产生布洛芬的极谱催化波。在该波的基础上，建立一种测定布洛芬的新方法。结论 该方法灵敏，快速，简便。     

单剂量及多剂量口服布洛芬缓释胶囊的药物动力学与生物等效性研究

在20名健康男性志愿者中研究两种布洛芬缓释胶囊的药动学和生物等效性。采用双周期随机交叉试验设计,LC-MS法测定人血浆中布洛芬的浓度。单剂量口服受试和参比制剂后血浆中布洛芬的Cmax分别为(19.21±3.49)和(16.86±4.30)μg/ml,tmax分别为(5.00±0.73)和(4.85±0.67)h,t1/2分别为(2.45±0.52)和(3.42±1.17)h,以AUC0→24h计算得受试制剂的相对生物利用度为(101.74±10.52)%;多剂量试验的Cmax分别为(17.58±4.38)和(14.46±3.61)μg/ml,tmax分别为(4.68±1.13)和(4.68±1.46)h,t1/2分别为(3.01±0.77)和(3.60±0.82)h,DF分别为(176.05±32.33)和(138.00±25.55)%,以AUC0→24h计算得受试制剂的相对生物利用度为(99.09±11.13)%。表明两种布洛芬缓释胶囊生物等效。     

壳聚糖-海藻酸钠布洛芬缓释微球的制备工艺及性能

目的 研究以壳聚糖和海藻酸钠为基质材料,制备布洛芬缓释微球. 方法 以微球的药物包封率为制备工艺优化指标.利用复凝聚法,通过L16(45)正交实验得出微球的最佳制备工艺条件. 结果 壳聚糖浓度4.0 mg/mL,搅拌速度600 r/min,反应温度30℃,体系pH 4.5,交联剂戊二醛用量1.5 mL为最佳工艺.以最佳制备工艺条件制备的布洛芬缓释微球.粒径(31.6±1.7)μm,药物包封率(64.6±2.2)%. 结论 微球球形态及稳定性较好,有良好的缓释效果.     

美林混悬液的临床疗效观察

目的　为选择既能有效及时地控制高热、又能简便服用的药物,观察美林混悬液的临床疗效,并与安乃近注射液进行比较。方法　应用随机对照的方法,对有高热症状的急性上呼吸道感染患儿(直肠体温≥39.5℃),分别用美林混悬液和安乃近注射液治疗,并观察两药的临床疗效。结果　在第1h 内美林混悬液和安乃近注射液的退热效果及退热速度相同,美林混悬液在第2h 起使患儿体温降至接近正常体温,并能维持8h;安乃近注射液从用药后4h 起体温有回升。结论　美林混悬液退热作用强,维持时间长,对咽痛、头痛也有显著的缓解疗效     

The effect of combined therapy for treatment of monotherapy-resistant PDA in preterm infants

Objective: Hemodynamically significant PDA (hsPDA) is one of the most common problems in preterm infants. This study was conducted to investigate the effect of combined pharmacological (paracetamol?+?ibuprofen) therapy on monotherapy-resistant hsPDA in infants.

Subject and methods: The study included infants with persistent hsPDA, unresponsive to monotherapy. Combined treatment (paracetamol?+?ibuprofen) was started as paracetamol at a dose of 15?mg/kg every 6?hours for 5?days, and ibuprofen at an initial dose of 10?mg/kg followed by 5?mg/kg at 24 and 48?hours. Echocardiographic evaluation was performed at 2?days after the end of treatment. If hsPDA persisted after the combined treatment, a surgical PDA ligation was considered.

Results: A total of 12 infants were enrolled and 9 infants (75%) with monotherapy-resistant PDA were successfully treated with combined therapy. In three patients, no response was obtained to the combined treatment so surgical ligation was applied.

Conclusions: Combined therapy may be a useful treatment option for monotherapy-resistant hsPDA in preterm infants. Before surgical ligations, this combined therapy option should be considered.     

The efficacy of pain control following nonsurgical root canal treatment using ibuprofen or a combination of ibuprofen and acetaminophen in a randomized, double-blind, placebo-controlled study

AIM: To compare ibuprofen, to an ibuprofen/acetaminophen combination in managing postoperative pain following root canal treatment. It is hypothesized that the drug combination will provide more postoperative pain relief than the placebo or ibuprofen alone. METHODOLOGY: Patients presenting at the Texas A&M Baylor College of Dentistry's graduate endodontic clinic, experiencing moderate to severe pain, were considered potential candidates. Fifty-seven patients were included based on established criteria. Following administration of local anaesthesia, a pulpectomy was performed. The patients were administered a single dose of either: (i) placebo; (ii) 600 mg ibuprofen; or (iii) 600 mg ibuprofen and 1000 mg of acetaminophen. Patients recorded pain intensity following treatment on a visual analogue scale and a baseline four-point category pain scale as well as pain relief every hour for the first 4 h then every 2 h thereafter for a total of 8 h. A general linear model (GLM) analysis was used to analyse the outcome. RESULTS: Based upon the GLM analysis, there was a significant difference between the ibuprofen and the combination drug group, and between placebo and combination drug groups. There was no significant difference between the placebo and the ibuprofen. CONCLUSION: The results demonstrate that the combination of ibuprofen with acetaminophen may be more effective than ibuprofen alone for the management of postoperative endodontic pain.     

Encapsulation of water-insoluble drug by a cross-linking technique: Effect of process and formulation variables on encapsulation efficiency, particle size, and in vitro dissolution rate

Ibuprofen-gelatin micropellets were prepared by the cross-linking technique using formaldehyde. Spherical micropellets having an entrapment efficiency of 65% to 85% were obtained. The effect of core to coat ratio, speed of agitation, temperature, and volume of oil phase was studied with respect to entrapment efficiency, micropellet size, and surface characteristics. Fourier transform infrared spectroscopy and differential scanning calorimetric analysis confirmed the absence of any drug-polymer interaction. X-ray diffraction patterns showed that there is a decrease in crystallinity of the drug. The micromeritic properties of micropellets were found to be slightly changed by changing various processing parameters to give micropellets of good flow property. The in vitro release profile could be altered significantly by changing various processing parameters to give a controlled release of drug from the micropellets. The stability studies of the drug-loaded micropellets showed that the drug was stable at storage conditions of room temperature, 37 degrees C, 25 degrees /60% relative humidity (RH) and 45 degrees /60% RH, for 12 weeks.     

Influence of age on the enantiomeric disposition of ibuprofen in healthy volunteers

AIMS: To determine the influence of age on the enantioselective disposition of ibuprofen in humans. METHODS: Healthy young (n = 16; aged 20-36 years) and elderly (n = 16; aged 66-84 years) volunteers were given a 400-mg oral dose of racemic ibuprofen, and blood and urine samples were collected for 24 h post drug administration. Serum concentrations, total and free, and urinary excretion of both enantiomers of ibuprofen together with the urinary excretion of the stereoisomers of the two major metabolites of the drug, both free and conjugated, were determined by high-performance liquid chromatography. RESULTS: Ageing had little effect on the distribution and metabolism of R-ibuprofen, unbound clearance of the R-enantiomer via inversion being approximately two-fold that via noninversion mechanisms in both age groups. In contrast, the free fraction of S-ibuprofen was significantly greater [33%; young 0.48 +/- 0.10%; elderly 0.64 +/- 0.20%] mean difference -0.16; 95% confidence interval (CI) -0.05, -0.27; P < 0.01; and the unbound clearance of the drug enantiomer was significantly lower (28%; young 15.9 +/- 2.2 l min-1; elderly 11.5 +/- 4.1 l min-1; mean difference 4.4; 95% CI 2.12, 6.68; P < 0.001) in the elderly. The metabolite formation clearances of S-ibuprofen via glucuronidation, and oxidation at the 2- and 3- positions of the isobutyl side chain decreased by 24, 28 and 30%, respectively, in the elderly compared with the young, the differences between the two age groups being significant in each case (P < 0.05). CONCLUSIONS: Following administration of racemic ibuprofen age-associated stereoselective alterations in drug disposition have been observed, with the elderly having increased free concentrations and lower unbound clearance of the S-enantiomer in comparison with the young. In contrast, the handling of the R-enantiomer is essentially unaltered with age. The results of this study indicate that the elderly have an increased exposure to the active ibuprofen enantiomer and thus some caution may be required when using this drug in this age group.