Evaluation of blank film forming polymeric dispersions based on Eudragit RL 30D and RS30D for transdermal drug delivery

The first approved transdermal drug delivery system in the United States in 1979 is a scopolamine patch for treatment of motion sickness. Transdermal drug delivery system has many advantages over oral route such as it is useful for vomiting and unconscious patients. It can avoid first pass metabolism by the liver. It is non-invasive way and self-administered system compared to injections. The film forming polymeric solutions are a novel transdermal drug delivery system. This system consists of an active drug, film forming polymer, plasticizer.

Shear-augmented solute dispersion during drug delivery for three-layer flow through microvessel under stress jump and momentum slip-Darcy model

Nanoparticle(drug particle) dispersion is an important phenomenon during nanodrug delivery in the bloodstream by using multifunctional carrier particles. The aim of this study is to understand the dispersion of drug particle(nanoparticle) transport during steady blood flow through a microvessel. A two-phase fluid model is considered to define blood flow through a microvessel. Plug and intermediate regions are defined by a non-Newtonian Herschel-Bulkley fluid model where the plug region appears due to the aggregation of red blood cells at the axis in the vessel. The peripheral(porous in nature)region is defined by the Newtonian fluids. The wall of the microvessel is considered to be permeable and characterized by the Darcy model. Stress-jump and velocity slip conditions are incorporated respectively at the interface of the intermediate and peripheral regions and at the inner surface of the microvessel. The effects of the rheological parameter, the pressure constant, the particle volume fraction, the stress jump constant, the slip constant,and the yield stress on the dispersion are analyzed and discussed. It is observed that the non-dimensional pressure gradient and the yield stress enhance the dispersion rate of the nanoparticle, while the opposite trends are observed for the velocity slip constant, the nanoparticle volume fraction, the rheological parameter, and the stress-jump constant.

1例鼻-眶-脑型毛霉菌病患者的药学监护

目的 为鼻-眶-脑型毛霉菌病(ROCM)的临床诊疗和药学监护提供思路。方法 临床药师参与1例ROCM患者的诊断和治疗过程,结合相关治疗指南及药物可及性、经济性等实际情况,协助医生制定两性霉素B胆固醇硫酸酯复合物联合泊沙康唑的抗真菌治疗方案,并监测临床疗效、肝肾功能及电解质变化。根据外周血和脑脊液检查结果,临床药师建议给予两性霉素B脱氧胆酸盐鞘内注射、滴鼻、滴眼以提高感染灶局部药物浓度,并协助医生确定给药剂量及药液配制方法;针对泊沙康唑血药谷浓度不达标的问题,临床药师建议将泊沙康唑口服混悬液更换为泊沙康唑肠溶片,并对患者进行治疗药物监测(TDM)、个体化用药指导及出院长期随访。结果 医生采纳了临床药师的建议。患者经治疗后,病情好转,准予带药出院。结论 临床药师通过调整药物剂量和剂型、开展用药监护和TDM等药学服务手段,为ROCM患者制定个体化治疗方案,有助于保障患者用药的安全性。

首都国医名师王沛基于固摄法辨证治疗卵巢癌之经验

文中总结王沛教授基于固摄法治疗卵巢癌之经验。王沛教授认为卵巢癌病因病机为下焦不通-癌毒内生而失固,肝郁肾虚-正气亏虚而耗散,癌毒生长发展而成卵巢癌。肝郁肾虚为卵巢癌之根本病机,外寒、湿热、瘀血、痰饮为卵巢癌形成主要病理因素,癌毒生而失固属卵巢癌发生发展之关键环节。基于“散”与“失固”理论,王沛教授提出了固摄法治疗卵巢癌,以固癌摄瘤防转移,配合攻毒祛邪除癌毒,兼滋肾疏肝固正气为根本原则。并善用虫药,兼顾护脾胃,临床疗效显著。文末附验案1则以佐证。

固体分散体在改善药物溶出度方面的研究进展

固体分散体技术可用于改善难溶性药物的溶出和吸收,本文作者概述了固体分散体的概念、重要性和发展概况以及存在的问题。结合美国橙皮书对已上市的以固体分散体技术制备的药物进行了总结。对应用较多的热熔挤出法和喷雾干燥法及发展较快的超临界流体技术的原理、关键工艺参数及特点加以说明,说明了相应方法制备得到的固体分散体对药物溶出度的影响,并对其他部分方法进行补充。最后,分析了固体分散体老化问题。旨在为研究固体分散体在改善溶出方面的科研工作者提供方向和科研思路。

载多西紫杉醇米替福新固体分散体的表征

目的考察米替福新固体分散体中多西紫杉醇的载药、增溶和溶出行为。方法以米替福新为载体材料,通过共溶液-溶剂挥发法制备载多西紫杉醇的固体分散体,差示热分析和热重分析考察米替福新和多西紫杉醇的复合行为、X-射线衍射分析考察材料表面的复合情况,高效液相色谱-紫外分光光度法测定多西紫杉醇的增溶和溶出量并绘制累积释放量经时曲线。结果差示热分析-热重分析曲线和X-射线衍射图谱结果均显示随着米替福新中多西紫杉醇的从无到有、从少到多,曲线和图谱中米替福新的特征逐渐减少,而多西紫杉醇的特征逐渐增多。当多西紫杉醇载量为40%以下时,其能够完全被米替福新增溶,当多西紫杉醇载量在50%及以上时,只有部分多西紫杉醇能够被增溶,且增溶过程需要约2 h。结论以米替福新为固体分散体的载体材料可以复合多西紫杉醇,并且可以在一定载量下对多西紫杉醇进行完全或部分增溶。

基于改性壳聚糖膜净化的超高效液相色谱-四极杆/静电场轨道阱质谱法测定牛奶中5种兽药残留

本研究通过在壳聚糖膜(chitosan membrane,CSM)表面接枝长碳链,获得了十八烷基三甲氧基硅烷改性的壳聚糖膜(C_(18)-CSM),将其作为分散固相萃取吸附剂对牛奶基质进行净化,并结合超高效液相色谱-四极杆/静电场轨道阱质谱(UHPLC-Q/Exactive Orbitrap MS)建立了牛奶中氧氟沙星、恩诺沙星、环丙沙星、地西泮和甲硝唑的测定方法。利用扫描电子显微镜、傅里叶变换红外光谱仪和接触角测试仪对C_(18)-CSM材料进行表征。对牛奶样品的前处理条件进行优化,最优条件如下:提取溶剂为5%甲酸乙腈,NaCl用量为1 g,萃取次数为1次,C_(18)-CSM用量为20 mg。采用Hypersil GOLD VANQUISH色谱柱(100 mm×2.1 mm,1.9μm)进行分离,以0.1%甲酸水溶液和0.1%甲酸乙腈作为流动相进行梯度洗脱,流速为0.3 mL/min,进样量为1μL,柱温为25℃,在电喷雾电离源正离子模式下进行检测。在优化的前处理条件下,5种兽药在0.5~100μg/L范围内具有良好的线性关系,相关系数(r^(2))≥0.9970,检出限(LOD)为0.2μg/L,定量限(LOQ)为0.5μg/L。5种兽药在3个加标水平(0.5、1、5μg/L)下的回收率为79.5%~115%,日内精密度为7.0%~13%(n=6),日间精密度为1.3%~11%(n=3)。实验结果表明,本文所建立方法操作简便,准确可靠,能够满足牛奶中5种兽药残留的同时检测。

基于“玄府-络脉”理论探讨糖尿病性勃起功能障碍的病机及治疗方法

基于“玄府-络脉”理论,阐述玄府-络脉的生理功能及病理表现,提出玄府闭塞,络脉瘀血为糖尿病性勃起功能障碍的核心病机。玄府闭塞,脏腑功能失调,精微失布,发为消渴,病程日久,内生糖毒,损伤络脉,衍生阳痿。因此,治疗时引入风类药辛散开玄以治其本,虫类药活血通络以治其标,标本兼治,则诸症皆除,为中医从微观结构层次治疗该病提供新思路。

基于R语言的专利中药复方防治呼吸道传染病的用药规律研究

【目的】挖掘专利中药复方防治呼吸道传染病的遣方用药规律,为呼吸道传染病的防治提供参考。【方法】在国家专利数据库中收集防治呼吸道传染病的中药复方,经数据筛选与规范化后,利用R语言进行数据挖掘。【结果】共纳入429首中药专利复方,涉及中药846味;高频中药有26味,使用频次居前10位的药物分别为甘草、金银花、黄芩、连翘、桔梗、百部、苦杏仁、黄芪、柴胡、薄荷。高频中药主要为清热解毒药和补气药;所涉中药药性以寒为主,药味多为苦、甘、辛,主归肺经;关联规则分析得到19条核心关联规则、多个药物组合;聚类分析得到3个药物聚类。【结论】专利中药复方防治呼吸道传染病时注重寒温相配、宣降相伍,着重宣散肺邪、清热解毒,同时不忘益气和中、滋阴润燥,使祛邪不伤正、扶正不敛邪。

Improved dissolution of Kaempferia parviflora extract for oral administration by preparing solid dispersion via solvent evaporation

Kaempferia parviflora, a plant in the family Zingiberaceae, has been used in Thai traditional medicines for treating hypertension and promoting longevity with good health and wellbeing. However, its limited aqueous solubility and low dissolution restrict its bioavailability.The aim of the study was therefore to improve the dissolution rate of K. parviflora extracted with dichloromethane(KPD) by solid dispersions. Different water-soluble polymers were applied to improve dissolution of KPD. The solid dispersions in different ratios were prepared by solvent evaporation method. Only hydroxypropyl methylcellulose(HPMC) and polyvinyl alcohol-polyethylene glycol grafted copolymer(PVA-co-PEG) could be used to produce homogeneous, powdered solid dispersions. Physical characterization by scanning electron microscopy, hot stage microscopy, differential scanning calorimetry and powder X-ray diffractometry, in comparison with corresponding physical mixtures, showed the changes in solid state during the formation of solid dispersions. Dissolution of a selected marker,5,7,4′-trimethoxyflavone(TMF), from KPD/HPMC and KPD/PVA-co-PEG solid dispersions was significantly improved, compared with pure KPD. The dissolution enhancement by solid dispersion was influenced by both type and content of polymers. The stability of KPD/HPMC and KPD/PVA-co-PEG solid dispersions was also good after 6-month storage in both longterm and accelerated conditions. These results identified that the KPD/HPMC and KPD/PVAco-PEG solid dispersions were an effective new approach for pharmaceutical application of K. parviflora.

Dispersive liquid-liquid microextraction,an effective tool for the determination of synthetic cannabinoids in oral fluid by liquid chromatography-tandem mass spectrometry

In the present work,dispersive liquid-liquid microextraction(DLLME)was used to extract six synthetic cannabinoids(JWH-018,JWH-019,JWH-073,JWH-200,or WIN 55,225,JWH-250,and AM-694)from oral fluids.A rapid baseline separation of the analytes was achieved on a bidentate octadecyl silica hydride phase(Cogent Bidentate C18;4.6 mm×250 mm,4μm)maintained at 37℃,by eluting in isocratic conditions(water:acetonitrile(25:75,V/V)).Detection was performed using positive electrospray ionization-tandem mass spectrometry.The parameters affecting DLLME(pH and ionic strength of the aqueous phase,type and volume of the extractant and dispersive solvent,vortex and centrifugation time)were optimized for maximizing yields.In particular,using 0.5 mL of oral fluid,acetonitrile(1 mL),was identified as the best option,both as a solvent to precipitate proteins and as a dispersing solvent in the DLLME procedure.To select an extraction solvent,a low transition temperature mixture(LTTM;composed of sesamol and chlorine chloride with a molar ratio of 1:3)and dichloromethane were compared;the latter(100μL)was proved to be a better extractant,with recoveries ranging from 73%to 101%by vortexing for 2 min.The method was validated according to the guidelines of Food and Drug Administration bioanalytical methods:intra-day and inter-day precisions ranged between 4%and 18%depending on the spike level and analyte;limits of detection spanned from 2 to 18 ng/mL;matrixmatched calibration curves were characterized by determination coefficients greater than 0.9914.Finally,the extraction procedure was compared with previous methods and with innovative techniques,presenting superior reliability,rapidity,simplicity,inexpensiveness,and efficiency.

Polymer-based nanoparticulate solid dispersions prepared by a modified electrospraying process

A modified electrospraying process is exploited to enhance the dissolution profiles of a poorly water-soluble drug. With polyvinylpyrrolidone (PVP) as a hydrophilic polymer matrix and ketoprofen (KET) as a model drug, polymer-drug composites in the form of nanoparticles were prepared and characterized. The surface morphologies, the physical status of the drug, and the drug-polymer interactions were studied using FESEM, DSC, XRD, and ATR-FTIR. FESEM observations demonstrated that the nanoparticles gradually decreased in size from 640 ± 350, to 530 ± 320, 460 ± 200 and 320 ± 160 nm as the KET content increased from 0, to 9.1%, 16.7% and 33.3% w/w, respectively. Results from DSC and XRD suggested that KET was distributed in the PVP matrix in an amorphous manner at the molecular level. This is thought to be due to their compatibility, arising through hydrogen bonding as demonstrated by ATR- FTIR spectra. In vitro dissolution tests showed that the nanoparticles released the incorporated KET within 1 min, evidencing markedly improved dissolution over pure KET and a KET-PVP physical mixture. Electrospraying can hence offer a facile route to develop new polymer composites for biomedical applications, in particular for improving dissolution rate of poorly water-soluble drugs.

Development and characterization of nifedipine-amino methacrylate copolymer solid dispersion powders with various adsorbents

Solid dispersions of nifedipine(NDP), a poorly water-soluble drug, and amino methacrylate copolymer(AMCP) with aid of adsorbent, that is, fumed silica, talcum, calcium carbonate,titanium dioxide, and mesoporous silica from rice husks(SRH), were prepared by solvent method. The physicochemical properties of solid dispersions, compared to their physical mixtures, were determined using powder X-ray diffractometry(PXRD) and differential scanning calorimetry(DSC). The surface morphology of the prepared solid dispersions was examined by scanning electron microscopy(SEM). The dissolution of NDP from solid dispersions was compared to NDP powders. The effect of adsorbent type on NDP dissolution was also examined. The dissolution of NDP increased with the ratio of NDP:AMCP:adsorbent of 1:4:1 when compared to the other formulations. As indicated from PXRD patterns, DSC thermograms and SEM images, NDP was molecularly dispersed within polymer carrier or in an amorphous form, which confirmed the better dissolution of solid dispersions. Solid dispersions containing SRH provided the highest NDP dissolution, due to a porous nature of SRH, allowing dissolved drug to fill in the pores and consequently dissolve in the medium.The results suggested that solid dispersions containing adsorbents(SRH in particular) demonstrated improved dissolution of poorly water-soluble drug when compared to NDP powder.

液相色谱-串联质谱法同时测定鸡蛋中4种抗病毒药物残留

建立液相色谱-串联质谱法同时测定鸡蛋样品中4种抗病毒药物(金刚烷胺、金刚乙胺、利巴韦林和吗啉胍)残留量的分析方法。鸡蛋样品残留的目标物质通过1%甲酸乙腈提取,经MgSO4、N-丙基乙二胺(primary secondary amine,PSA)、十八烷基硅胶C18和石墨化炭黑(graphitized carbon black,GCB)分散固相萃取净化,40℃水浴中氮气吹干后复溶。采用色谱柱Shim-pack Velox HILIC(2.1×150 mm,2.7μm),流动相A为乙腈,B为20 mM甲酸铵+0.1%甲酸溶液,进行梯度洗脱,4种目标物质正离子模式监测,内标法定量进行分析。结果显示,4种抗病毒药物在一定浓度范围内线性良好,相关系数(R2)均大于0.9960,检出限在0.1~1.5μg/kg范围之间,定量限在0.3~4.0μg/kg范围之间。4种药物在各自定量限1、1.5、2倍添加浓度水平下添加回收率在75.9%~110.1%之间,相对标准偏差(relative standard deviations,RSDs)为3.2%~6.9%。该方法操作简单、灵敏度高、回收率好,可用于日常鸡蛋样品中抗病毒类药物的残留检测。

脂肪酸基天然低共熔溶剂悬浮固化分散液-液微萃取/液相色谱法检测水样和人尿中抗真菌药

建立了基于新制备的天然低共熔溶剂悬浮固化(SFNADES)分散液-液微萃取结合高效液相色谱法(HPLC)检测环境样品中酮康唑、克霉唑、特比萘芬和益康唑4种抗真菌药的分析方法。选用月桂酸为氢键供体,正辛醇为氢键受体合成的天然低共熔溶剂(NADES)作为萃取剂。通过优化萃取剂的种类与摩尔比、萃取剂体积、样品体积、样品pH值与离子强度、涡旋时间及离心时间等获得了最佳萃取效率。在最优条件下,方法的线性范围为0.56~500μg/L,线性系数(r^(2))≥0.999 8,检出限为0.17~0.80μg/L,定量下限为0.56~2.67μg/L,富集倍数为101~114,日内和日间相对标准偏差(n=6)分别不大于4.8%和5.4%。该方法已成功用于实际水样和人尿中抗真菌药的检测,回收率为91.5%~107%。

分散固相萃取技术在动物源性食品兽药残留检测中的应用进展

高效的样品前处理是实现准确分析的前提条件。分散固相萃取(dispersive solid-phase extraction,DSPE)是一种通过将固体吸附剂分散在液体分析物中,从复杂基质中分离和净化不同的分析物的方法。这种方法具有高效、快速、选择性强、易操作等优点,已经被广泛应用于环境、食品、药物、生物等领域的样品前处理中。本文首先对DSPE做了概述,然后以DSPE的设计原理为切入点,阐述固体吸附剂的不同分散方式、固体吸附剂的种类和性质对样品前处理过程的影响。随着纳米科技的蓬勃发展,尤其是磁性纳米材料、分子印迹聚合物、碳质材料及金属有机框架化合物等新材料的发现为DSPE注入了新的活力。本文重点讨论了这几种新材料在动物源性食品兽药残留方面的应用情况,并对DSPE的未来发展方向进行了预测,以期为相关技术人员提供新的思路。

分散液液微萃取/超高效液相色谱-四极杆/静电场轨道阱质谱法快速筛查化妆水中139种药物残留

建立了分散液液微萃取(DLLME)结合超高效液相色谱-四极杆/静电场轨道阱质谱(UPLC-Q Exactive Orbitrap MS)同时测定化妆水中抗生素、激素、禁用染料、农药以及真菌毒素5大类共139种药物残留的分析方法。考察了DLLME各条件对萃取效果的影响,确定最佳萃取条件为:取样量5.0 g,萃取剂为四氯乙烷(50μL)、分散剂为乙腈(300μL)、氯化钠用量为0.30 g、超声时间为8 min。样品经萃取后,采用岛津Shimpack XR-ODS II(150 mm×2.0 mm,2.2μm)色谱柱分离,通过Q-Exactive Orbitrap MS以全扫描确定母离子精确质量数的离子丰度,实现多种类目标物的定量,结合保留时间和子离子数据依赖模式扫描(DD-MS2)确定子离子的精确质量数,并配合谱库检索进行快速确证与筛查。结果表明:139种化合物的质量浓度在10~1000 ng/mL范围内与峰强度呈良好线性关系(r>0.99),检出限为10~30μg/kg,回收率为63.0%~95.9%,相对标准偏差(RSD)为3.0%~9.5%;各精确质量数偏差小于3×10^(-6)。该方法稳定、简单、快速、精确,有机试剂用量少,环境友好,适用于化妆水的快速筛查。

Fundamental aspects of solid dispersion technology for poorly soluble drugs

The solid dispersion has become an established solubilization technology for poorly water soluble drugs.Since a solid dispersion is basically a drug-polymer two-component system,the drug-polymer interaction is the determining factor in its design and performance.In this review,we summarize our current understanding of solid dispersions both in the solid state and in dissolution,emphasizing the fundamental aspects of this important technology.

分散固相萃取-超高效液相色谱-串联质谱法同时测定豆芽中96种药物残留

建立了优化的分散固相萃取前处理方法,结合超高效液相色谱-串联质谱法同时测定豆芽中植物生长调节剂类、抗生素类、杀菌剂类共96种药物残留的方法。样品经1%(体积分数)甲酸乙腈提取,无水硫酸钠及氯化钠盐析,C18吸附剂净化。采用C18色谱柱分离,以乙腈-5 mmol/L乙酸铵溶液(含体积分数为0.1%的甲酸)为流动相进行梯度洗脱,正负离子同时扫描,动态多反应监测模式,基质匹配标准曲线外标法定量。结果表明,96种化合物在各自质量浓度范围内线性良好,相关系数均大于0.990,方法定量限在5~50μg/kg,样品在10、50、200μg/kg 3个添加水平的平均加标回收率分别为75.8%~117.7%、64.3%~114.5%和64.3%~114.4%,相对标准偏差分别为2.3%~12.9%、1.2%~14.1%和2.4%~17.5%。应用建立的方法对72批次的豆芽样品进行筛查分析,检出19批次阳性样品,有8种药物检出。该方法简便快捷,准确可靠,目标物覆盖范围广,能有效地评估豆芽中药物残留的种类和含量水平,为豆芽中药物残留的风险监控提供技术支持。

模块药盒装填位置及药粒散布状态对内弹道特性影响的数值模拟研究

为了优化模块装药的装药设计,深入分析单模块装药的内弹道稳定深层机理,针对单模块装药模块药盒的不同装填位置及药盒破碎后火药颗粒的散布状态对压力波等内弹道特性的影响规律展开研究,基于经典内弹道理论建立模块装药一维气-固两相流内弹道模型,采用MacCormack差分方法进行数值计算,对比分析其内弹道参量在时间、空间上的变化规律。对模块药盒初始位置距膛底距离为0,100,200,300,400和500 mm的6种工况下的内弹道过程进行了数值计算及分析对比,发现模块药盒不同初始装填位置对内弹道特性有一定的影响。随着模块药盒离开膛底距离增大,膛内最大压力先增大后减小、弹丸初速也先提高后降低,在药盒初始位置距膛底100 mm时达到最大压力和最高弹丸初速;对模块药盒破碎后药粒在膛内的均匀散布、线性散布和后堆式散布等3种状态下的内弹道过程进行了数值模拟及分析。结果表明,药粒的均匀散布与线性散布对内弹道参量影响不大,而药粒的后堆散布会延长整个燃烧过程,同时降低膛压峰值和弹丸出口速度。