芹菜素茶油微乳的制备及其透皮性能的考察

通过溶解度实验和不同辅料之间的配伍实验确定芹菜素茶油微乳的组成成分。通过绘制伪三元相图确定芹菜素茶油微乳的微乳区域。通过星点设计-效应面法确定芹菜素茶油微乳的最优处方:即由22.71%的茶油/GTCC(1∶1,w/w),60.19%Cremorphor RH40,17.1%PEG400组成油相混合物,每克油相混合物中加入35 mg芹菜素,经蒸馏水稀释20倍后得到最终微乳液。初步透皮实验表明,芹菜素茶油微乳12 h单位面积累积经皮渗透量(Q_(12 h))为79.47μg·cm~(-2),透皮速率常数(J)为6.45μg·cm~(-2)·h~(-1),较芹菜素茶油溶液有所提高。     

当归油对白及多糖微凝胶贴片中α-熊果苷体外透皮行为的影响

研究了当归油对白及多糖微凝胶贴片中α-熊果苷的促渗透作用,为挥发油作为透皮促进剂在日化、医药领域的进一步应用提供依据。采用涂膜法制备以白及多糖为基质的α-熊果苷微凝胶贴片,采用HPLC法测定α-熊果苷含量;采用立式扩散池考察当归油对α-熊果苷经皮渗透的影响规律;采用DSC分析给药前后皮肤角质层的结构特征变化,以揭示当归油促进药物透皮吸收的机理。所制备的白及多糖微凝胶贴片外观细腻,柔软,有韧性,体外透皮试验显示,随着处方中当归油浓度的增加,α-熊果苷的累积透过量逐渐增加,促渗作用增强,当当归油浓度达到1.0%时,α-熊果苷的累积透过量较对照组提高了1.89倍。DSC分析显示,随着处方中当归油浓度的增大,皮肤的特征峰逐渐变弱,当当归油的加入量达1.0%时,皮肤角质层的特征峰消失。当归油具有良好的透皮促进作用,1.0%当归油对α-熊果苷促渗作用最佳,当归油可作为一种天然透皮促进剂,具有良好的应用前景。     

几种挥发油对黄藤素透皮给药的促渗作用研究

为给黄藤素透皮给药选择合适的挥发油促渗剂,以高效液相色谱法测定黄藤素的含量,采用立式扩散池法研究桉叶油、艾叶油、当归油、连翘油对黄藤素透皮给药的影响;实验结束后,用DSC扫描观察皮肤的特征峰变化。结果表明,5 h时,艾叶油组药物的累积透过量分别是被动扩散组、桉叶油组、当归油组、连翘油组的1.82,1.16,1.48,1.63倍,药物的累积渗透量随着艾叶油浓度的增加而增加,艾叶油浓度1.5%时,其促渗能力最强。DSC图谱表明,不同挥发油对皮肤的特征峰具有不同的影响,促渗能力较好的挥发油使皮肤的特征峰消失;当艾叶油的浓度由0.5%增加到1.5%,DSC图谱发生相应变化,浓度为1.5%和2.0%时具有相似的图谱,而浓度为2.5%时的DSC图谱与0.5%的图谱相似。艾叶油能够显著促进黄藤素的透皮给药,且最佳的浓度为1.5%,其机理可能是通过扰乱或破坏皮肤角质层的有序结构来增强皮肤对药物的渗透性,因此,艾叶油可作为黄藤素透皮给药的理想促渗剂而具有广泛的应用前景。     

几种挥发油对黄藤素透皮给药的促渗作用研究

为给黄藤素透皮给药选择合适的挥发油促渗剂,以高效液相色谱法测定黄藤素的含量,采用立式扩散池法研究桉叶油、艾叶油、当归油、连翘油对黄藤素透皮给药的影响;实验结束后,用DSC扫描观察皮肤的特征峰变化。结果表明,5 h时,艾叶油组药物的累积透过量分别是被动扩散组、桉叶油组、当归油组、连翘油组的1.82,1.16,1.48,1.63倍,药物的累积渗透量随着艾叶油浓度的增加而增加,艾叶油浓度1.5%时,其促渗能力最强。DSC图谱表明,不同挥发油对皮肤的特征峰具有不同的影响,促渗能力较好的挥发油使皮肤的特征峰消失;当艾叶油的浓度由0.5%增加到1.5%,DSC图谱发生相应变化,浓度为1.5%和2.0%时具有相似的图谱,而浓度为2.5%时的DSC图谱与0.5%的图谱相似。艾叶油能够显著促进黄藤素的透皮给药,且最佳的浓度为1.5%,其机理可能是通过扰乱或破坏皮肤角质层的有序结构来增强皮肤对药物的渗透性,因此,艾叶油可作为黄藤素透皮给药的理想促渗剂而具有广泛的应用前景。     

O/W型微乳的制备及其对皮肤刺激性的检测

通过拟三元相图微乳区大小筛选微乳制备组分的较佳配比,电导率法检测微乳的类型,研究了以十四酸异丙酯、十六酸异丙酯、大豆油为油相,吐温80和卵磷脂质量比以及乙醇、1,2-丙二醇为助表面活性剂对微乳形成区域的影响。结果表明:选用十六酸异丙酯作油相,吐温80和卵磷脂质量比为2∶1作混合表面活性剂,乙醇为助表面活性剂时能形成较大的O/W型微乳区。经动物实验证实能够满足药用无毒、无刺激性要求,适合作为透皮吸收药物载体。     

新型纳米级乳膏的处方研究

目的:制备乳粒为纳米级的纳米乳膏。方法:通过油相组成的筛选、混合乳化剂的筛选以及绘制伪三元相图确定微乳区,确立纳米乳膏的最终处方。结果:选取水相和油相(6:1)共占60%,乳化剂Cremophor EL为25%,辅助乳化剂为15%为最终处方。其中油相为单硬脂酸甘油酯:硬脂酸:液体石蜡(4:2:1,w/w/w),水相为水:甘油(20:1,w/w),制得的乳膏中乳粒的平均粒径为115.7 nm。结论:通过处方筛选,我们制得的乳膏其乳粒的粒径位于纳米级水平。     

当归精油的促透皮吸收作用研究

当归为伞形科多年生草本植物当归Angelica sinensis (Oliv.)Diels的根。研究发现超临界萃取法提取当归得率较高为2.5%,且对进行动物皮肤刺激性实验,结果表明均为中等刺激。以黄芩苷为模型药物进行透皮吸收促进作用研究,结果表明当归油对黄芩苷均有一定的促透作用,在化妆品行业中具有较好的开发应用前景。     

二醇型人参皂苷W/O纳米乳的制备及其抗皮肤衰老机制研究

制备二醇型人参皂苷W/O纳米乳,研究其抗皮肤衰老机制。根据伪三元相图形成的纳米乳区和二醇型人参皂苷的溶解性,筛选二醇型人参皂苷纳米乳的处方;测定纳米乳的形态、粒径分布、载药量及稳定性。采用Franz扩散池研究纳米乳的体外透皮特性,HE染色法考察雄性小鼠局部给药对皮肤微观结构的影响,并考察纳米乳的抗皮肤衰老功效。二醇型人参皂苷W/O纳米乳的最佳处方为棕榈酸异丙酯(油相)、司盘80(乳化剂)、1,2-丙二醇(助乳化剂)、K_m值=2、油相与混合乳化剂比例为7.5∶2.5;制得的纳米乳外观圆整、均匀,平均粒径为17 nm,粒径分布系数为0.064,二醇型人参皂苷含量为4.2 mg/m L,且物理稳定性良好。体外透皮实验结果表明,给药12 h后二醇型人参皂苷纳米乳的累计透过量为1.640 7 mg/cm~2,皮肤滞留量为0.018 4 mg/cm~2,分别为二醇型水溶液的2.832 2倍和1.179 5倍;HE染色实验发现,使用人参皂苷纳米乳后结构基本完整,无病理学病变,真皮胶原纤维致密丰富,多排列成束。动物实验结果表明,二醇型人参皂苷纳米乳高、中、低剂量组的羟脯胺酸、Ⅰ型胶原、Ⅲ型胶原、基质金属蛋白酶抑制剂1(TIMP-1)、基质金属蛋白酶抑制剂2(TIMP-2)含量均显著大于空白组和二醇型人参皂苷水溶液组,基质金属蛋白酶1(MMP-1)含量显著小于空白组和二醇型人参皂苷水溶液组。制备的人参皂苷纳米乳稳定性好,透皮性能优良,能通过抑制皮肤内胶原蛋白分解,提高皮肤中胶原蛋白含量达到抗皮肤衰老功效。     

面膜中荧光增白剂的透皮吸收特性及对皮肤刺激性的实验研究

为了研究含脂溶性荧光增白剂（FWAs）面膜的透皮吸收特性及其对皮肤刺激性,采用改良的Franz透皮扩散池,以离体雄性大鼠腹部皮肤为模型,通过高效液相色谱-三重四极杆液质联用法测定接收液中5种吡唑啉型荧光增白剂的含量,计算其不同透皮时间段的累计渗透量,并对试验终期皮肤中FWAs的贮留量进行检测;按《化妆品安全技术规范》（2015年版）中皮肤刺激性实验要求,采用家兔进行皮肤刺激性试验。结果显示,5种脂溶性FWAs呈现良好的线性关系,相关系数（r²）均大于0.999,检出限为0.5～10.0 pg,定量限为2.0～30.0 pg,平均回收率和相对标准偏差分别为95.2%～102.1%和1.8%～4.2%。面膜中的脂溶性荧光增白剂C.I.162有较强的透皮能力可以进入皮下,在0～36 h内透皮扩散符合零级动力学方程;而C.I.135、C.I.185、C.I.367、C.I.368四种FWAs短期内均被皮肤吸收而未透过皮肤。结果提示,脂溶性FWAs较易迁移到皮肤的角质层或皮下,对哺乳动物皮肤没有刺激作用。     

复方丁香油自微乳化 给药系统的制备及体外评价

目的:研究复方丁香油自微乳化给药系统的处方并对其进行质量评价。方法:通过油相和表面活性剂配伍试验、伪三元相图的工艺初步筛选,以乳化时间、平均粒径及分散指数(PDI)为指标,确定复方丁香油自微乳的处方组成;通过复方丁香油自微乳的粒径、Zeta电位和不同温度条件下的稳定性评价其体外质量。结果:复方丁香油自微乳处方中油相为复方丁香油(14.6%),乳化剂为吐温-80(68.3%),助乳化剂为1,2-丙二醇(17.1%)。自微乳化后粒径为23nm,zeta电位为-35±5.7。结论:制备的复方丁香油自微乳的粒径小、粒径分布均匀、乳化后系统稳定性好,为其临床应用推广奠定基础。     

Formulation and Evaluation of Polymeric Nanoparticulate Gel for Topical Delivery

The aim of the present study was to enhance the permeation of drug into the skin and to reduce the skin irritation. To achieve the objective the drug was formulated in to nanoparticles using chitosan as a polymer and these drug loaded nanoparticles were incorporated in gel. The prepared nanoparticles were characterized by FTIR, DSC, SEM, and particle size. The particle size for optimized nanoparticulate gel (NPG-4) was found to be between 49–305nm. SEM photographs showed that nanoparticles were roughly spherical in shape and free from cracks. The NPG-4 showed 43.9% of encapsulation efficiency and 18.9% drug loading. At the end of 24h the in vitro drug release was found to be 90.1% in pH 7.4 phosphate buffer saline (PBS) and in vitro skin permeation studies NPG-4 showed 2.1mg/cm² of drug permeation, which was better than the marketed formulation (NIZRAL 2%) cream, which showed only 1.2mg/cm² of drug permeation. The NPG-4 showed no primary skin irritation when tested on rabbit skin.     

MMA反相微乳液体系的稳定性及相结构表征

采用电导率法,测定了以表面活性剂丁二酸-2-乙基己基磺酸钠(AOT)与甲基丙烯酸甲酯(MMA)和水构成的反相微乳液体系的稳定性,考察了油相极性、表面活性剂浓度、分散相浓度及离子价态、助乳化剂丙烯酰胺(AM)对反相微乳液体系的影响,确定了反相微乳液体系体系的局部相图,初步表征了反相微乳液体系的相结构。结果表明,以极性单体作为油相的微乳液体系电导率与增溶水量的变化关系中不存在突变点,有别于一般的以低极性或非极性烷烃(或混合烷烃)作为油相的微乳液体系。当体系中AOT浓度0.1~0.3 M,分散相(盐溶液)浓度≤0.05 M,增溶水量([H2O]/[AOT]摩尔比)w≤9时,可以得到稳定的反相微乳液体系,AM的存在能够增大体系的增溶能力。     

纳米微乳化薄荷香精的制备及应用研究

采用纳米微乳化技术,经单因素和正交试验筛选得到了优化的制备工艺。得到优化制备条件为：在30℃恒温水浴下,薄荷油载量为12%（质量分数,下同）,乳化剂用量为12%（其中T20为10%,P1570为2%）,助乳化剂PG用量为20%,PEG-400用量为5%,去离子水为51%,剪切乳化速度为5 800r/min。产品理化指标为：外观澄清泛蓝光,水溶性良好,为O/W型微乳,粒径≤100nm,相对密度为1.0270,折光率为1.3944,薄荷油实际载量为（11.0±0.5）%,30℃时包封率为90%,在60℃条件下较稳定。     

40％敌敌畏·毒死蜱复配制剂的研究

通过对乳化剂、助乳化助剂、稳定剂、溶剂以及助溶剂的研究筛选,确定了适合的制备工艺,并测定热贮前后敌敌畏分解率变化。结果表明,该制剂在的分解率在14％-16％左右,低于目前市场上已有产品30％-50%A的分解率。该优化配方为敌敌畏（40％）、毒死蜱（10％）、20LOCX（8％）、D625（4％）、抗氧101（3％）、抗水1≠≠（3％）、稳1撑（3％）、150#溶剂油补至100％。     

Phase Behavior of Non-Ionic Surfactant-Medium Chain Triglyceride-Water Microemulsion Systems

Microemulsion systems have garnered tremendous interest in the pharmaceutical sector for a variety of drug delivery applications. Non-ionic surfactants are often the preferred surfactant class given their uncharged nature, enhanced oral safety profile, and generally regarded as safe status as compared to other surfactant classes (Myers, Surfactant science and technology, 2005, p. 29), (Malmsten, Handbook of microemulsion science and technology, 1999, p. 755), (Grove & Mullertz, Chapter 5-liquid self-microemulsifying drug delivery systems, 2007), (Liu et al., Water-insoluble drug formulation, 2008), (Hauss, Advanced Drug Delivery Reviews, 2007, 59, pp. 667–676), (Balazs, Solubility, delivery and ADME problems of drugs and drug-candidates, 2011, p. 68). In this work, the phase behavior and microemulsion formation potential of four commonly used non-ionic surfactants, PEG-40 hydrogenated castor oil, Poloxamer 188, Polysorbate 80, and d -α-tocopherol polyethylene glycol succinate were studied via ternary phase diagram (TPD) mapping using a medium chain triglyceride, Miglyol 812. Results indicated notable differences in phase behavior despite similarities in hydrophilic–lipophilic balance value (13–15). All surfactants produced Winsor Type I, oil-in-water microemulsions at water concentrations above 40% wt/wt. Winsor Type II water-in-oil microemulsions were difficult to obtain even at high oil concentrations of ≥70% wt/wt. Winsor III microemulsions, though rare, were generally obtained in the middle regions of the TPD between 10% and 30% wt/wt water while Winsor IV microemulsions dominated at high surfactant concentrations of ≥45% wt/wt. Opaque emulsion areas were particularly notable in wax state surfactants. Polysorbate 80 and PEG-40 hydrogenated castor oil demonstrated a high degree of synergism as well as the largest oil-in-water (o/w) and water-in-oil (w/o) microemulsion formation potential rendering them suitable for a number of enteral and parenteral applications.     

Development of Phospholipids Vesicular Nanocarrier for Topical Delivery of Tea Tree Oil in Management of Atopic Dermatitis Using BALB/c Mice Model

This work aims to develop and evaluate the efficacy of tea tree oil (TTO) ethosomal cream with improved deposition in skin layers for treatment of atopic dermatitis (AD). Ethosomes of TTO are developed using phosphatidylcholine (2% and 3% w/v) and ethanol (20%, 30%, and 40% w/v). Ethosomes are evaluated for percent entrapment efficiency (%EE), vesicle size, zeta potential, and in vitro drug diffusion. Ethosomal creams with optimized ethosomal dispersion are developed and evaluated for physicochemical parameters, thermal stability, ex vivo permeation, skin retention, and in vitro cytotoxicity using HaCat skin cell lines in comparison to conventional creams of TTO. In vivo investigations of optimized creams are performed using BALB/c mice model. The %EE, vesicle size, and zeta potential for optimized ethosomes are found to be 76.19 ± 3.26%, 333.6 nm, and –35.3 mV, respectively. Ethosomal creams showed higher deposition in the epidermis and dermis. The optimized creams are non-cytotoxic to HaCat cell lines. The creams significantly reduce the inflammatory response by decreasing the clinical score and infiltration of white blood cells, eosinophils, and IgE antibodies. Overall efficacy of ethosomal cream is higher than conventional cream. In conclusion, optimized ethosomal cream of TTO shows good efficacy for treatment of AD. Practical applications : The method used for the formulation of ethosomes is simple and can be easily scaled up on the industrial level. The loading of TTO within ethosomes can increase the efficiency by enhanced drug deposition in the epidermis and might also improve its stability against oxidative degradation. Topical ethosomal cream of TTO can improve patient compliance by avoidance of adverse effects linked with corticosteroids and could be a possible complementary or alternative therapy in management of AD.     

Development of topical gel containing aceclofenac-crospovidone solid dispersion by “Quality by Design (QbD)” approach

This article describes the development, optimization, and evaluation of Carbopol 940 topical gel containing aceclofenac-crospovidone (1:4) solid dispersion using “Quality by Design (QbD)” approach based on 2³ factorial design. The effect of crospovidone, tri-ethanolamine, and ethyl alcohol amount on the drug permeation profile of the topical gel containing aceclofenac-crospovidone solid dispersion was optimized by 2³ factorial design. The optimized gel showed improved permeation profile with cumulative drug permeation of 26.262 ± 2.157%, and permeation flux of 0.059 ± 0.011 μg/cm²/h. These gels were characterized by pH, viscosity, gel strength and FTIR study. The in vivo anti-inflammatory activity of the optimized gel was evaluated in rats using carrageenan-induced rat-paw oedema model and found excellent anti-inflammatory comparable with a marketed gel without producing any skin irritation.     

磺化合成鲸蜡油/硫酸酯类表面活性剂复合体系的性能研究

以降膜式SO3磺化合成鲸蜡油(SSW)为对象,考察了磷酸酯类表面活性剂(PES)对SSW形成复合体系的影响。通过比较拟三元相图中油相区域比例,确定3种SSW/PES复合体系中PES的最优用量:w(A8EO5PNa)=1.5%,w(A9EO5PNa)=1.0%,w(A12EO3PNa)=0.5%。根据最优配方研究了复合体系的表面张力、革表面动态润湿角、乳液稳定性、临界胶束浓度(cmc)及粒度分布。结果表明:SSW/A9EO5PNa复合体系表面张力为27.39 mN/m,润湿渗透能力强,临界胶束浓度低,乳液稳定性好,乳液平均粒径为78.7 nm,更适合应用于皮革加脂剂。     

毛蕊花挥发油成分分析及其在卷烟中的应用

采用水蒸气蒸馏法,对毛蕊花中挥发油进行提取。测得毛蕊花挥发油得率为0.6%。并用气相色谱/质谱联用技术进行分析鉴定,鉴定出58种化学成分,应用峰面积归一法确定了各成分的相对含量。水蒸气蒸馏法提取的毛蕊花挥发油主要含苧烯(31.28%)、小茴香酮(22.17%)、桉叶素(9.25%)、反式石竹烯(6.63%)、α-艹律草烯(6.4%)、蒎烯(3.24%)、胡椒烯酮醚(3.01%)等。用毛蕊花挥发油进行了卷烟加香试验,结果表明毛蕊花挥发油具有改善卷烟香气、增加清香香韵、降低刺激性的作用,毛蕊花挥发油可用于卷烟加香。     

吐温-80/正丁醇/环己烷/水系微乳液性能及对木材的渗透能力

考察了吐温-80/正丁醇/环己烷/水系微乳液各组分及其质量比对其形成的影响,通过电导率、表面张力和动态光散射(DLS)表征体系的物化性质。结果表明,以吐温-80为表面活性剂,正丁醇为助表面活性剂,环己烷为油相形成的微乳区较大。微乳体系的电导率随含水量的增加呈现规律性变化,可以判断微乳液的3种类型(油包水型、双连续型和水包油型);不同类型的微乳液均具有较低的表面张力(约24.6 mN/m)和粒径(小于100nm),且粒径随体系含水量的增加而增大。此外,采用液体吸收法考察了微乳液对木材的渗透能力,与普通溶剂相比,微乳液具有很强的渗透能力,特别是对于双连续型微乳液,10 min时,对马尾松和桉木的渗透能力分别达70%和50%。