双氯酚酸钠脂质体的制备及其眼部药代动力学

目的研究双氯酚酸钠脂质体的制备方法并考察其在家兔眼部的药代动力学特征。方法采用逆相蒸发法制备双氯酚酸钠正电荷脂质体。脂质体和滴眼液滴眼后家兔采用高效液相色谱法测定角膜前、角膜和房水中药物浓度。结果制得的脂质体平均粒径为226.5 nm，多分散度为0.214，ζ电位为+18.1 mV，经均匀设计优化处方，包封率可达到63%。0.1%双氯酚酸钠脂质体和滴眼液两种制剂家兔局部滴眼后的药代动力学研究显示，脂质体可延缓药物在角膜前的清除，增加角膜中药物的浓度，药物在房水中半衰期延长，以滴眼液为参比制剂，相对生物利用度为211%。结论双氯酚酸钠正电荷脂质体可以增加药物在角膜前的滞留时间，提高角膜渗透性及药物在眼部的生物利用度，减少滴眼次数。     

双氯芬酸钠肠溶微丸型片剂的研制

本文制备了双氯芬酸钠肠溶微丸型片剂。以丙烯酸树脂EudragitNE30D和EudragitL30D-55不同比例的混合物作为衣膜材料，对不同粒径大小的双氯芬酸钠速释丸芯进行不同增重水平的包衣，并与不同压缩特性和用量比例的缓冲微丸混合，压片。所得的双氯芬酸钠肠溶微丸型片剂在人工胃液中2 h内累积释放百分数<10%，在人工肠液中1 h内累积释放百分数为(83±2.42)%。结果表明EudragitNE30D与EudragitL30D-55以一定比例混合制备得到适合压片的肠溶微丸，硬脂酸制备的缓冲微丸可用于微丸型片剂的制备。     

The effect of terpene concentrations on the skin penetration of diclofenac sodium

Terpenes and sesquiterpenes have been suggested as promising non-toxic, non-irritating transdermal penetration enhancers. This investigation aimed to study the effect of terpene concentration on the transdermal absorption of diclofenac sodium from ethanol:glycerin:phosphate buffer solution (60:10:30). Therefore, enhancing effects of various terpenes (menthone, limonenoxide, carvone, nerolidol and farnsol) with different concentrations (0.25, 0.5, 1, 1.5 and 2.5%, v/v) on the permeation of diclofenac sodium were evaluated using Franz diffusion cells fitted with rat skin. Furthermore, solubility of diclofenac sodium in the vehicle in presence of different concentrations of terpenes was determined. The results showed that despite the negligible effect of terpenes on the drug solubility, there was a profound skin penetration enhancement effect, although the terpene enhancers varied in their ability to enhance the flux of diclofenac sodium. The results showed that at the highest concentration of terpene (2.5%, v/v) the rank order of enhancement effect for diclofenac sodium was nerolidol>farnesol>carvone>methone>limonenoxide, whereas at the low concentration of 0.25% the rank order was farnesol>carvone>nerolidol>menthone>limonenoxide. No direct relationship existed between terpene concentration and the permeation rate. The most outstanding penetration enhancer was nerolidol, providing an almost 198-fold increase in permeability coefficient of diclofenac sodium, followed by farnesol with a 78-fold increase.     

HPLC法测定双氯芬酸钠凝胶中双氯芬酸钠的含量

目的采用HPLC法测定双氯芬酸钠凝胶中双氯芬酸钠的含量。方法以十八烷基键合硅胶为填充剂;用甲醇-0.005 mol/L磷酸二氢钾溶液(p H=3.8)(70∶30)为流动相;检测波长:280 nm;流速:1.0 m L/min;外标法测峰面积定量。结果双氯芬酸钠在15.90~55.41μg/m L(r=0.999 0)范围内线性关系良好,平均回收率为100.48%,RSD为1.28%。结论本方法简便、快速、准确,可用于双氯芬酸钠凝胶中双氯芬酸钠的含量测定。     

The effect of polymer blends on release profiles of diclofenac sodium from matrices.

The purpose of this study was to evaluate the effect of polymer blends on the in vitro release profile of diclofenac sodium. Several controlled release matrices of diclofenac sodium with different proportions of hydroxypropyl methylcellulose (HPMC; viscosity grade 60 and 500 mPa.s), carbopol 940 and lactose as a water soluble filler were prepared. The results showed that when HPMC (viscosity grade 60 mPa.s) alone was used as matrix former, diclofenac sodium was released fast but the release rate became slower with HPMC (viscosity grade 500 mPa.s) at higher polymer/drug ratios (more than 0.8:1). However in lower polymer/drug ratios (lower than 0.7:1) the release rate still was fast. The results showed that carbopol can extend the release time appreciably but the release profiles had considerable fluctuations, and drug release in first hours was slow but increased appreciably with time at the end of profiles. When an appropriate blend of HPMC (viscosity grade 60 or 500 mPa.s) and carbopol 940 was used, the drug release became more uniform and its kinetic approached to zero order and release fluctuations were diminished. The results with these polymer blends showed that it is possible to reduce the total amounts of polymer in each formulation. According to kinetic analysis data, drug release from these matrix tablets did not follow Fick's law of diffusion and the results were in agreement with the earlier reports.     

双氯芬酸钠超前镇痛用于骨外科手术的临床效果观察

目的：观察骨科手术患者应用双氯芬酸钠超前镇痛的有效性和安全性。方法将50例骨科手术患者随机分为观察组与对照组各25例。观察组于术前36、24、12h 均给予双氯芬酸钠100mg 纳肛,对照组术前不给药物。术后患者使用自控镇痛泵。记录2组患者术后2、6、12、24、48h 的视觉模拟评分（VAS 评分）,并比较2组有效按压次数、镇痛满意度评分（NRS 评分）、术后48h 曲马多用量及不良反应。结果镇痛期间呼吸、循环功能稳定,无异常出血等严重并发症发生,2组患者在各时间点的 BP、SpO2、HR 和 RR 之间比较差异无统计学意义（P ﹥0.05）。观察组患者术后2、6、12h 的静息 VAS 评分低于对照组,差异有统计学意义（P ﹤0.05）;而2组24h 和48h 的静息 VAS 评分比较差异无统计学意义（P ﹥0.05）。术后观察组患者48h 内 PCA 按压次数低于对照组,镇痛满意度评分高于对照组,但2组差异均无统计学意义（P ﹥0.05）。术后48h 内,观察组曲马多的使用次数少于对照组,用量低于对照组,差异均有统计学意义（P ﹤0.05）。结论双氯芬酸钠超前镇痛用于骨外科手术,可有效缓解术后疼痛,提高患者镇痛满意度,减少术后镇痛药的使用。     

Enhancing effect of terpenes on the in vitro percutaneous absorption of diclofenac sodium

The enhancing effect of naturally occurring terpenes on the in vitro percutaneous absorption of diclofenac sodium (DFS) from carbopol gels containing propylene glycol was investigated. Permeation experiments were performed on excised abdominal rat skin. Terpenes varied in their activities: the alcohol terpenes were effective accelerants for the drug whereas the ketones were much less efficient, providing only a 2-to-3-fold increase in DFS diffusion; limonene showed mild accelerant activity and 1,8-cineole was a poor accelerant. Acyclic alcohols were found to be the best enhancers for DFS, being geraniol, with an almost 20-fold increase, the most outstanding penetration enhancer. However, although the addition of terpenes increased DFS flux, diffusional lag times were longer than for the control gel.     

Effect of sodium chloride on the gelation temperature, gel strength and bioadhesive force of poloxamer gels containing diclofenac sodium

Liquid suppository systems composed of poloxamers and bioadhesive polymers were easy to administer to the anus and mucoadhesive to the rectal tissues without leakage after the dose. However, a liquid suppository system containing diclofenac sodium could not be developed using bioadhesive polymers, since the drug was precipitated in this preparation. To develop a liquid suppository system using sodium chloride instead of bioadhesive polymers, the physicochemical properties such as gelation temperature, gel strength and bioadhesive force of various formulations composed of diclofenac sodium, poloxamers and sodium chloride were investigated. The mixtures of P 407 (15%) and P 188 (15-20%) existed as a liquid at room temperature, but gelled at physiological temperature. Diclofenac sodium significantly increased the gelation temperature and weakened the gel strength and bioadhesive force, while sodium chloride did the opposite. Furthermore, the poloxamer gels with less than 1.0% of sodium chloride, in which the drug was not precipitated, were inserted into the rectum of rabbits without difficulty and leakage, and retained in the rectum of rats for at least 6 h. Our results suggested that a thermosensitive liquid suppository system with sodium chloride and poloxamers was a more physically stable and convenient rectal dosage form for diclofenac sodium.     

氮酮对双氯灭痛透皮吸收的影响

以透皮吸收模型观察了氮酮浓度对双氯灭痛透皮吸收的影响。结果表明，搽剂中氮酮浓度为１％是其透皮吸收促进作用的适宜浓度，氮酮对软膏中双氯灭痛的透皮吸收无促进作用。     

The effect of glycyrrhizin on the release rate and skin penetration of diclofenac sodium from topical formulations

The influence of glycyrrhizin extracted from Glycyrrhiza glabra var. glandulifera (licorice roots) on the percutaneous absorption of diclofenac sodium from sodium carboxymethylcellulose (NaCMC) gels or oil-in-water (o/w) emulsion was investigated. Skin permeation experiments were carried out using excised abdominal rat skin. The results showed that the efficiency of glycyrrhizin as an enhancer agent is greater in gel formulations than it is in the emulsions. The enhancer with the concentration of 0.1% w/w in gel increased diclofenac sodium flux value to tenfold compared with the control gel.     

The effect of glycyrrhizin on the release rate and skin penetration of diclofenac sodium from topical formulations

The influence of glycyrrhizin extracted from Glycyrrhiza glabra var. glandulifera (licorice roots) on the percutaneous absorption of diclofenac sodium from sodium carboxymethylcellulose (NaCMC) gels or oil-in-water (o/w) emulsion was investigated. Skin permeation experiments were carried out using excised abdominal rat skin. The results showed that the efficiency of glycyrrhizin as an enhancer agent is greater in gel formulations than it is in the emulsions. The enhancer with the concentration of 0.1% w/w in gel increased diclofenac sodium flux value to tenfold compared with the control gel.     

齐多夫啶半乳糖神经酰胺脂质体的制备及理化性质研究

目的 制备齐多夫啶半乳糖神经酰胺脂质体并对其理化性质进行研究。方法 采用两次乳化法，以半乳糖神经酰胺为主要膜材制备齐多夫啶半乳糖神经酰胺脂质体并进行形态学观察、检测其包封率和稳定性。结果 透射电子显微镜下观察齐多夫啶半乳糖神经酰胺脂质体为粒径均匀的球形或近球形的小单层颗粒；粒径范围为60～270nm，D50为140nm；包封率达72．5％，但10d后快速下降。结论 齐多夫啶半乳糖神经酰胺脂质体制备方法可行，需进一步提高包封率和稳定性。     

The effect of dimensions on the compaction properties of sodium chloride

Using a tablet press instrumented with strain gauges, anhydrous particulate sodium chloride was compressed to form compacts of different lengths in three dies of different diameters. For the limited range of dimensions applicable to most pharmaceutical tablets, there was a common linear relation between the applied compaction pressure and the force lost to the die wall per unit area of apparent die wall contact, during compression. Ejection forces were correlated using a similar expression. The mechanical strength of compacts was determined by diametrical compression. A relation was proposed to express the strength (F_e), of the compacts of different sizes in terms of the diametrical cross-sectional area at zero porosity (D.L_o), the relative volume (V_r) and the mean compaction pressure (P_m): , where k and c are constants.     

双氯芬酸钠脂质体凝胶剂的研制

目的 :研制双氯芬酸钠脂质体凝胶 ,并进行评价。方法 :运用薄膜蒸发法制备了双氯芬酸钠脂质体 ,然后用卡波姆 (Carbopol)为基质制得凝胶。并建立了一阶导数紫外分光光度法进行测定。结果 :测得样品低、中、高 3个浓度的平均回收率分别为 (10 1 1± 0 86 ) % ,(99 90± 1 0 4 ) %和 (10 0 5± 0 91) %。脂质体经凝胶柱分离后测得平均包封率为 4 3 6 % ,经库尔特计数器测得平均粒径为 1 37μm。凝胶分别于冰箱 (4℃ )和室温下密封保存 0 5、1、3、6mo ,6mo后的包封率下降分别为 4 4 %、6 8%。结论 :经初步评价 ,将双氯芬酸钠制成脂质体凝胶剂是可行的     

Nanocapsule@xerogel microparticles containing sodium diclofenac: a new strategy to control the release of drugs

The aim of this work was to evaluate the potentiality to control the drug release of a new architecture of microparticles organized at the nanoscopic scale by assembling polymeric nanocapsules at the surface of drug-loaded xerogels. Xerogel was prepared by sol-gel method using sodium diclofenac, as hydrophilic drug model, and coated by spray-drying. After coating, the surface areas decreased from 82 to 28 m(2)/g, the encapsulation efficiency was 71% and SEM analysis showed irregular microparticles coated by the nanocapsules. Formulation showed satisfactory gastro-resistance presenting drug release lower than 3% (60 min) in acid medium. In water, the pure drug dissolved 92% after 5 min, uncoated drug-loaded xerogel released 60% and nanocapsule coated drug-loaded xerogel 36%. After 60 min, uncoated drug-loaded xerogel released 82% and nanocapsule coated drug-loaded xerogel 62%. In conclusion, the new system was able to control the release of the hydrophilic drug model.     

Effect of sodium diclofenac on the bioavailability of amoxicillin

The aim of this study was to evaluate the effect of sodium diclofenac on the bioavailability of amoxicillin. In this randomised, crossover study with a 1-week washout period, 20 volunteers received a 2g oral dose of amoxicillin (Amoxil) (Group 1) or a 2g oral dose of amoxicillin with 100 mg of sodium diclofenac (Voltaren) (Group 2). Blood samples were collected at 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 and 24h following drug administration. High-performance liquid chromatography with ultraviolet detection was used to quantify plasma amoxicillin concentrations. Bioassay (Micrococcus luteus ATCC 9341) was performed to verify the antimicrobial efficacy of amoxicillin in vitro. The pharmacokinetic parameters area under the plasma concentration-time curve (AUC), maximum plasma concentration observed during the 24-h study period (C(max)) and renal clearance (CL) were analysed by analysis of variance, and time at which C(max) occurred (T(max)) and volume of distribution (VD) were analysed by Wilcoxon test (P<0.05). For Group 1, the mean (+/- standard deviation) AUC(0-24), C(max) and T(max) values were 3391.8+/-1186.7 microg min/mL, 17.3+/-6.5 microg /mL and 121.5+/-20.6 min, respectively; and for Group 2, the values were 2918.4+/-1024.8 microg min/mL, 15.5+/-5.8 microg /mL and 136.5+/-30.0 min, respectively. Lower values of AUC and C(max) were observed for Group 2 (P<0.05). CL of amoxicillin increased (P< 0.05) by 18.5% in Group 2, suggesting that sodium diclofenac may interfere with amoxicillin renal excretion. In conclusion, sodium diclofenac can significantly reduce the bioavailability of amoxicillin.     

A study of the effect of aspirin on the pharmacokinetics of oral and intravenous diclofenac sodium

Summary Previous studies have shown that aspirin interacts with orally administered diclofenac sodium, causing reduced peak concentrations, lower levels and decreased areas under curves. In this study, diclofenac sodium was administered orally and intravenously with and without aspirin, to 6 healthy female volunteers. After intravenous dosing both plasma levels and areas under curves were significantly reduced although none of the rate constants was affected. The volume of distribution of diclofenac was increased as was the plasma clearance. Oral administration with aspirin also resulted in lower plasma levels, particularly peak levels, and areas under curves. Comparison of AUC's for both modes of administration with and without aspirin suggested that lower levels after oral administration were not due to impaired absorption. These observations are best explained by decreased protein binding and increased biliary excretion of diclofenac in the presence of salicylate.     

双氯芬酸钠缓释制剂的释放度考察

目的:考察双氯芬酸钠缓释制剂的体外释放度.方法:采用转篮法和pH6.8的人工肠液对市售4个厂家的双氯芬酸钠缓释片和缓释胶囊的释放度进行了测定,并对释放度数据进行方程拟合及t检验.结果:A、C厂家产品的释放规律较符合Weibull方程,而B、D厂家产品的释放规律较符合Higuchi方程.各厂家产品的释放度在1 h,6 h时差异有显著性,在12 h时差异无显著性.结论:不同厂家双氯芬酸钠缓释制剂的释放度差异存在显著性.