布洛芬注射液的制备及其稳定性考察

目的:通过影响因素试验和配伍稳定性试验考察自制布洛芬注射液的稳定性.方法:以精氨酸作为助溶剂,与布洛芬按1∶1摩尔比配制布洛芬注射液;通过影响因素试验(强光、高温和冻融试验),考察注射液稳定性;与0.9%氯化钠注射液和5%葡萄糖注射液配伍,考察24 h内的配伍稳定性.结果:制得的布洛芬注射液无色澄明,pH值在7.8左右;经影响因素试验考察,各指标无明显变化;配伍稳定性实验结果显示,与两种输液配伍后24 h内,配伍液外观和pH值均无明显变化,布洛芬含量基本没有变化,有关物质检查合格.结论:制备的布洛芬注射液经影响因素考察稳定性良好,与两种输液在25℃、24 h内配伍稳定.     

阿司匹林精氨酸盐注射液的制备及其稳定性研究

目的　制备阿司匹林精氨酸盐及其注射液 ,并测定含量 ,考察稳定性。方法　阿司匹林与精氨酸反应生成阿司匹林精氨酸盐 ,精制后以注射用水为溶剂制成阿司匹林精氨酸盐注射液 ,用紫外 -可见分光光度法测定其含量 ,考察阿司匹林精氨酸盐及其注射液在 30 ,4 5 ,6 0℃及 30 ,35 ,4 0 ,4 5℃的稳定性。结果　阿司匹林精氨酸盐在高温下不稳定 ,初步确定其注射液的有效期为 1.32年。结论　阿司匹林精氨酸盐及其注射液制备方法可行 ,其原料及制剂在常温下稳定     

复方曲马多注射液的制备及稳定性检定

目的:研究复方曲马多注射液的处方及制备工艺,并进行稳定性考察.方法:以曲马多、奈福泮含量、pH值为考察指标,筛选处方及制备工艺;并考察3批样品的稳定性.结果:最适pH值为5.0～6.0,制备的3批样品经加速试验6个月、室温留样24个月考察,质量稳定.结论:处方合理,工艺可行,质量稳定.     

右旋布洛芬β-环糊精包合物分散片的制备

目的: 优选右旋布洛芬β-环糊精包合物分散片的处方组成与制备工艺。方法: 单因素试验考察填充剂、崩解剂的选择;比较崩解时间;根据分散片的要求,以10 min的累积溶出度和崩解时间为评价指标,采用L₉(3⁴)正交试验对处方进行筛选;优选制备工艺并对处方与工艺进行重复性考察。结果: 右旋布洛芬β-环糊精包合物分散片的最佳处方组成:右旋布洛芬β-环糊精包合物 50%,MCC 22.5%,乳糖10.5%,PVPP 10%,L-HPC 5%。结论: 右旋布洛芬β-环糊精包合物分散片处方设计简单合理,工艺稳定,重复性好。     

布洛芬氯化钠注射液的研制

目的根据临床需要研究开发布洛芬氯化钠注射液,按照药品注册有关办法,筛选制剂处方和确定工艺参数,并建立其质量控制方法,考察其初步稳定性。方法对助溶剂、渗透压、pH值、活性炭用量等进行筛选,优化处方组成;对活性炭吸附条件和灭菌条件等参数进行验证,确认制备工艺;对制剂的性状、鉴别、pH值、有关物质和含量等项目进行研究,建立质量控制方法;影响因素试验考察其初步稳定性。结果通过处方筛选、工艺的参数验证以及影响因素试验,确定了最佳处方和制备工艺。按照优化出来的最佳处方及工艺,制备3批样品,并对其产品质量进行检测,结果均合格。结论该制剂处方合理,制备工艺可行,质量可控,初步稳定性良好。     

布洛芬液体胶囊的处方筛选及体外溶出的评价

目的筛选布洛芬液体胶囊处方,并采用高效液相色谱法对其进行溶出度考察。方法以液体胶囊的稳定性、崩解时限、体外溶出度为指标进行正交试验。结果最佳工艺处方为：甘油50mg,聚乙二醇100mg,吐温8010mg,氢氧化钠14mg。所制得的液体胶囊稳定,药物溶出快。结论布洛芬液体胶囊处方主要与氢氧化钠的用量有关。布洛芬液体胶囊与市售片剂相比,其溶出速率有明显提高。     

左卡尼汀注射液的制备及质量控制

目的：制备左卡尼汀注射液,并对该制剂进行质量控制。方法：拟定处方组成与制备工艺,进行性状、鉴别、pH、含量测定等质量研究,加速试验考察其稳定性。结果:按照优化的处方工艺,制备三批中试样品样品,并对质量进行检测,结果均合格;三批样品经6个月加速试验考察,该方法制备的左卡尼汀质量无明显变化。结论：本品处方设计合理,工艺可行,质量稳定。     

硫酸庆大霉素注射液处方和工艺研究

目的 研究硫酸庆大霉素注射液的处方和工艺,提高其Ph稳定性.方法 考察了配制浓料的注射用水温度、抗氧剂用量及其加入顺序对Ph稳定性的影响,按照最终确定的处方和工艺配制3批样品进行加速试验及长期稳定性试验.结果 在硫酸庆大霉素注射液生产中,配制浓料的注射用水温度和抗氧剂的加入顺序对Ph稳定性有影响,抗氧剂用量对Ph稳定性几乎无影响.结论 最终确定的处方和工艺比较合理,适用于大规模生产.     

布洛芬注射液的制备及与常用输液配伍的稳定性考察

目的考察布洛芬注射液与5%葡萄糖注射液和0.9%氯化钠注射液配伍的稳定性的研究。方法首先制备布洛芬注射液并考察其稳定性。通过与0.9%氯化钠注射液和5%葡萄糖注射液配伍,测定异物、微粒、pH以及指纹图谱,考察8 h内的配伍稳定性。结果布洛芬注射液无色、澄明,pH为7.82,经影响因素试验,各考察指标无明显变化。布洛芬注射液与0.9%氯化钠注射液或5%葡萄糖注射液配伍后,8 h内配伍液可见异物、不溶性微粒均符合规定,指纹图谱几乎没有变化,相似度均大于0.99。结论布洛芬注射液稳定性好,与0.9%氯化钠注射液或5%葡萄糖注射液配伍在8 h内稳定。     

依达拉奉注射液的制备工艺研究

目的 研究依达拉奉注射液的制备工艺.方法 采用HPLC筛选处方,通过相关试验考察工艺的稳定性.结果 依达拉奉注射液的最佳处方为每100ml溶液中添加亚硫酸钠200mg、L-盐酸半胱氨酸100mg,该品在pH为3.1～4.5下较稳定.结论 按照筛选出的处方和确定的工艺制备的依达拉奉注射液质量稳定.     

布洛芬L-抗坏血酸酯的合成及镇痛活性

布洛芬和L-抗坏血酸在叔丁醇中,用Novozym 435固定化脂肪酶催化制得布洛芬L-抗坏血酸酯,收率30%,纯度大丁98%.热板试验和乙酸扭体试验的结果表明,与布洛芬和布洛芬精氨酸盐相比,布洛芬L-抗坏血酸酯镇痛作用显著.     

A comparative study of the pharmacokinetics of ibuprofen arginate versus dexibuprofen in healthy volunteers

OBJECTIVE: Ibuprofen arginate is a salt formulation of ibuprofen designed to reach target concentrations rapidly. The primary objective of this study was to compare the 12-h pharmacokinetic profile of S(+)-ibuprofen following administration of single doses of ibuprofen arginate (600 mg) and dexibuprofen (400 mg) in healthy volunteers. METHODS: Twenty-four volunteers were recruited into an open-label, randomised, two-period, single-centre study with crossover design. RESULTS: Both treatments were well tolerated. Ibuprofen arginate and dexibuprofen showed similar bioavailability for S(+)-ibuprofen. Compared with dexibuprofen, ibuprofen arginate demonstrated a 45% higher maximum concentration (C(max)), and a time to peak concentration (T(max)) 2 h sooner. CONCLUSION: Ibuprofen arginate approaches maximum concentrations of S(+)-ibuprofen faster and higher than dexibuprofen.     

精氨洛芬片剂与颗粒剂在健康受试者体内的生物等效性

目的 研究精氨洛芬(非甾体抗炎药)片剂与颗粒剂在中国健康志愿者体内的生物等效性.方法 20名健康男性受试者分别随机交叉口服精氨洛芬片(试验制剂)及其颗粒(参比制剂)0.4 g,用HPLC-UV法测定给药后不同时间点的血浆布洛芬浓度;用DAS程序对试验数据进行统计处理,评价2种制剂的生物等效性.结果 试验制剂和参比制剂的药代动力学参数如下:Cmax分别为(50.60±9.12)、(50.53±8.58)nag·L-1,tmax分别为(0.51±0.20)、(0.34±0.11)h,AUC0～t分别为(118.63±21.42)、(115.75±20.23)mg·h·L-1,AUC0～∞分别为(121.18±22.18)、(118.55±21.83)mg·h·L-1.试验制剂与参比制剂AUC0-t之比和Cmax之比的90%可信区间分别为97.5%～107.6%和93.3%～107.2%.结论 试验制剂和参比制剂吸收程度等效(AUC0-t,AUC0-∞和Cmax均生物等效性);但吸收速度不等效(tmax不等效).     

L-精氨洛芬的制备

以布洛芬和L－精氨酸为原料，95％乙醇为反应溶剂，并在反应结束后以丙酮析晶得到L－精氨洛芬，收率可达90％以上。     

Pharmacokinetics of ibuprofen sodium dihydrate and gastrointestinal tolerability of short-term treatment with a novel, rapidly absorbed formulation

OBJECTIVE: This paper describes four studies investigating the dissolution, plasma pharmacokinetics and safety of a novel, fast-acting ibuprofen formulation, ibuprofen sodium dihydrate. MATERIAL AND METHOD: Four separate studies investigated: the in vitro dissolution rates of ibuprofen sodium dihydrate (at pH 1.2, 3.5 and 7.2); the bioavailability of ibuprofen sodium dihydrate (in two pharmacokinetic studies; combined n = 38) compared with conventional ibuprofen, ibuprofen lysinate, ibuprofen arginate and ibuprofen liquagels (all 2 x 200 mg ibuprofen); and the gastroduodenal tolerance of ibuprofen sodium dihydrate and ibuprofen arginate (both 2 x 200 mg ibuprofen t.i.d.) in an endoscopy safety study, where endoscopy was performed at baseline and at the end of each treatment period using a five-point scale to assess the integrity of the gastric and duodenal mucosa. RESULTS: Ibuprofen sodium dihydrate dissolved significantly more rapidly at pH 1.2, 3.5 and 7.2 than conventional ibuprofen, ibuprofen lysinate and ibuprofen liquagels. Ibuprofen sodium dihydrate had similar C(max) to ibuprofen lysinate and ibuprofen liquagels and significantly higher Cmax than conventional ibuprofen (p = 0.002). The mean plasma concentration for ibuprofen sodium dihydrate was significantly higher than for conventional ibuprofen (p = 0.028) 10 minutes post-dose and the t(max) for ibuprofen sodium dihydrate was reached significantly earlier than for conventional ibuprofen (p = 0.018). All three formulations were bioequivalent according to the acceptable boundaries (90% confidence intervals). No statistically significant difference was observed between the ibuprofen formulations in terms of adverse events and specifically with respect to hemorrhagic scores; 41 (46.0%) adverse events (AEs) occurred after administration of ibuprofen sodium dihydrate, and 46 (52.9%) after ibuprofen arginate. One occurrence of an invasive ulcer was observed after administration of ibuprofen arginate. CONCLUSIONS: The new formulation of ibuprofen sodium dihydrate dissolves quickly in vitro, has the same extent of absorption as other fast-acting ibuprofen formulations, and is absorbed into plasma more rapidly than conventional ibuprofen. In addition, the present studies suggest that the tolerability and safety profile of ibuprofen sodium dihydrate is comparable to existing ibuprofen formulations.     

Simultaneous fitting of R- and S-ibuprofen plasma concentrations after oral administration of the racemate

AIMS: To assess the pharmacokinetic equivalence of two different formulations of ibuprofen lysinate with special focus on the expected effects. METHODS: Sixteen healthy volunteers received cross-over ibuprofen lysinate as either one tablet of 400 mg ('test') or two tablets of 200 mg ('reference'). Ibuprofen plasma concentrations were followed up for 10 h. Bioequivalence was assessed by standard noncompartmental methods. Ibuprofen plasma concentrations were fitted with a model that took bioinversion of R- to S-ibuprofen into account. RESULTS: Peak plasma concentrations of R- and S-ibuprofen were 18.1 and 20 microg ml(-1) (test), and 18.2 and 20 microg ml(-1) (reference). Areas under the plasma concentration vs. time curves were 39.7 and 67.5 microg ml(-1) h (test), and 41.1 and 68.2 microg ml(-1) h (reference). Clearance of R-ibuprofen was 5.2 (test) and 5 l h(-1) (reference). A specific plasma concentration was reached with the test formulation about 5 min later than with the reference. Parameters from compartmental modelling were (given for R-and then for S-ibuprofen): body clearance: 4.9 and 4.64 l h(-1), central volume of distribution: 2.8 and 4.1 l, intercompartment clearance: 5.1 and 5.45 l h(-1), peripheral volume of distribution: 4.1 and 5.2 l. The absorption rate constant was 1.52 h(-1), and the test but not the reference formulation had a lag time of 0.1 h. Simulations showed similarity between formulations of the expected effects except for a calculated delay of 6 min with the test formulation. CONCLUSIONS: Ibuprofen formulations were bioequivalent. The pharmacokinetic model may serve as a basis for future pharmacokinetic/pharmacodynamic calculations after administration of racemic ibuprofen.     

Controlled release injectable liposomal gel of ibuprofen for epidural analgesia

The epidural administration is used commonly in the treatment of pain. Nonsteroidal anti-inflammatory drugs, especially ibuprofen, would have potential in epidural use. Like many epidurally useful drugs it, however, has a short duration of action, which is a limiting factor. To improve epidural pain treatment, a long-acting, single-dose gel injection is being developed. In the present study, the possibility of using liposomal systems to control the release and dural permeation of ibuprofen was investigated in vitro. Liposomal solutions of ibuprofen.Na (20 mg/ml) were prepared by high-pressure homogenization from egg phosphatidylcholine. The liposomal gel consisted of poloxamer 407 and the liposomal solution. No signs in the 1H-NMR spectroscopy of line broadenings or chemical shifts were observed. The liposomal formulations were reproducible and stable. Ibuprofen release in phosphate buffer, pH 7.4, at 37 degrees C from the liposomal solution and the liposomal gel were prolonged significantly compared with their respective solution and gel controls. The liposomal gel controlled ibuprofen release and dural permeation in vitro and showed a permeation pattern favourable for maintaining constant drug levels. The liposomal poloxamer gel represents a new formulation approach to increase the local epidural availability of ibuprofen. It appeared to be a promising injectable controlled-release drug delivery system.     

正交设计法优化布洛芬缓释骨架片的处方工艺

目的:制备布洛芬缓释骨架片并筛选其最佳工艺条件。方法:以累积释放百分率为考察指标,以羟丙甲纤维素(HPMC)、微晶纤维素(MCC)处方中用量及片剂的硬度等为考察因素,采用正交试验设计L9(34)进行处方和工艺优化。结果:优化布洛芬缓释骨架片处方工艺中HPMC、MCC处方中用量分别为12.5%、3.0%,片剂硬度为80 N;制备的3批布洛芬缓释骨架片可持续释放24 h,具有明显的缓释效果,其释放符合Higuchi方程(r>0.980 0)。结论:优化的工艺可行,可延长布洛芬的释药时间。     

Ibuprofen arginate provides effective relief from postoperative dental pain with a more rapid onset of action than ibuprofen

Ibuprofen is a safe and effective analgesic, but some formulations have a slow onset of action. Ibuprofen arginate is a rapidly absorbed salt designed to promote more rapid onset of analgesia. A clinical trial was conducted in 226 patients with postoperative dental pain to assess the analgesic efficacy and speed of onset of the arginine salt of ibuprofen compared with one of the commercially available forms of ibuprofen. Patients were administered a single dose of either ibuprofen arginate (200 mg or 400 mg), ibuprofen (200 mg or 400 mg), or placebo in this double-blind, randomized trial. To determine the onset of action of the study medication patients were required to note time to "any" pain relief and then time to "meaningful" pain relief, using the two-stopwatch method. Pain intensity and relief were assessed using traditional categorical scales over a 6-h period. Meaningful pain relief was achieved in 42 min and 24 min for ibuprofen arginate 200 mg and 400 mg, respectively, compared with 50 min and 48 min for ibuprofen 200 mg and 400 mg, respectively ( P<0.05). The results for the measurements of analgesic effectiveness [sum of pain intensity difference, total pain relief (TOTPAR), peak pain relief and overall evaluation of treatment] all showed that both doses of ibuprofen arginate and both doses of ibuprofen were significantly better than placebo and both 200-mg and 400-mg ibuprofen arginate doses were significantly better than ibuprofen 200 mg for peak pain relief. Mean plasma ibuprofen concentrations at 30 min and 60 min, respectively, were: ibuprofen arginine 200 mg, 13.9 micro g/ml and 15.7 micro g/ml; ibuprofen arginine 400 mg, 29.5 micro g/ml and 29.3 micro g/ml; ibuprofen 200 mg 2.5 micro g/ml and 5 micro g/ml; ibuprofen 400 mg, 2.3 micro g/ml and 7.4 micro g/ml. ( P<0.05). Adverse event profiles were similar across treatment groups. These results overall suggest that ibuprofen arginate when taken at doses equivalent to commercially available ibuprofen formulations produces analgesia that is faster in onset.