水包油型微乳形成因素的考察

目的考察影响O/W型微乳形成的主要因素。方法选用丁酸乙酯、油酸乙酯和豆油作为油相 ,Tween 80、Tween 2 0和Labrasol作为表面活性剂 ,乙醇、1,2 -丙二醇和正丁醇为助表面活性剂 ,通过滴加法绘制假三元相图 ,以O/W型微乳区大小为指标考察各因素对微乳形成的影响。结果油相、表面活性剂、助表面活性剂、表面活性剂与助表面活性剂的质量比、离子强度、添加剂和温度对微乳的形成均有一定影响。结论O/W型微乳能够作为药用载体。     

不同助表面活性剂对o/w型微乳形成的影响

在微乳配方开发过程中,通常选用短链醇作为助表面活性剂,然而有些药物在这些助表面活性剂中的溶解度或相容性并不理想.因此,选用非醇类物质(Plurol(R) Oleique CC 497、CapyrolTM 90或Transcutol(R))为助表面活性剂,并以Labrasol(R)为表面活性剂,Labrafil(R) M 1944为油相,分别绘制了空白微乳的伪三元相图.结果表明,这些助表面活性剂的种类和表面活性剂/助表面活性剂比例(Km)对o/w型微乳的形成有影响.     

卵磷脂微乳的制备与理化性质考察

目的：对25℃各卵磷脂系统中微乳的形成区域以及微乳理化性质随系统中各组分的变化情况进行研究。方法：卵磷脂作表面活性剂,短链醇类作助表面活性剂,采用不同油相考察相图中油包水型微乳形成区域的变化;选择不同处方组分的微乳测定微乳理化性质。结果：各个系统均可形成油包水型微乳,室温下放置数月未见分层。卵磷脂/醇质量比(K_m)与水相量对微乳的粘度有显著影响;电导率随着水相含量增加而增大;微乳的粒径随着体系中水相的增加而增大。结论：K_m较大,水相含量适中的微乳体系较为适合制备药物载体。     

非离子表面活性剂微乳的制备及抗菌性考察

目的:制备一种药用非离子表面活性剂空白微乳,并评价其抗菌性.方法:采用拟三元相图考察表面活性剂、助表面活性剂及其质量比、添加剂、温度等对微乳区的影响;高速离心法和37℃恒温1个月考察微乳稳定性;抗菌试验考察其抗菌能力.结果:油酸乙酯为油相、聚氧乙烯蓖麻油为表面活性剂、异丙醇为助表面活性剂的微乳区范围较大,可无限稀释;稳定性试验未见相分离;水相中的添加剂及温度的变化对微乳区范围无显著性影响;微乳均能有效杀灭绿脓杆菌、金黄色葡萄球菌、大肠杆菌、白色念珠菌,其中作用8 h后绿脓杆菌杀灭完全.结论:本品能自身抗菌,有可能成为适合眼用、注射等的潜在给药载体.     

利多卡因——卵磷脂微乳处方的初步研究

目的 :以卵磷脂微乳为载体 ,制备利多卡因透皮给药系统。方法 :伪三元相图考察油包水型微乳形成区域 ;测定微乳黏度 ,正交分析法筛选微乳处方 ;紫外分光光度法直接测定微乳中盐酸利多卡因浓度。结果 :助表面活性剂的种类和Km(表面活性剂 /助表面活性剂用量比 )对微乳形成区域有显著性影响 ,正丙醇和异丙醇所形成的微乳区较大 ;低纯卵磷脂微乳形成区域较高纯卵磷脂大 ;醇的种类对微乳的黏度均有显著的影响 ,Km 对微乳的黏度有较大影响。选定紫外检测波长为 2 6 2nm ,盐酸利多卡因浓度在 0 .0 2～ 0 .5mg/mL范围内线性关系良好 (R =0 .9999)。平均回收率 ( 10 0 .17± 0 .16 ) %。日内差与日间差分别为 0 0 137±0 0 12 1,0 0 119± 0 0 115。结论 :选择混合表面活性剂利于制备微乳 ,醇的种类与用量对于利多卡因透皮微乳体系处方的选择具有重要意义。     

萘普生口服微乳的制备及质量评价

目的：研制萘普生口服微乳制剂,并对其质量进行评价。方法考察萘普生在不同油相、表面活性剂和助表面活性剂中的溶解度,并通过滴定法绘制伪三元相图,根据相图优选处方,并初步考察微乳制剂的稳定性、形态粒径和理化性质。结果适宜的油相、表面活性剂和助表面活性剂分别为中链甘油三酯（ MCT）、聚山梨酸酯80（吐温80）和PEG400,三者之间的最适比例是1∶4.5∶1.5。结论该普生口服微乳制备简单,性质稳定,可显著增加萘普生的溶解度,为开发萘普生口服微乳提供了依据。     

微乳液相色谱法及其研究进展

微乳是由表面活性剂、油相、助表面活性剂、水相在适当比例下自发形成的一种透明或半透明的、低黏度的、各向同性且热力学稳定的水油混合系统。油相液滴（droplets）包裹于表面活性剂和助表面活性剂层并均匀分散在水相中,形成O／W型微乳;表面活性剂包裹水性液滴并分散在油相体系中形成W／O型微乳。微乳的研究主要集中在药剂学方面,用于药物分析方面的研究还比较少。微乳的粒径通常小于100nm,用于色谱流动相的微乳粒径可以小于10nm。微乳可以作为薄层色谱的展开剂和毛细管电泳的分离介质,也可以作为高效液相色谱的流动相,通常我们将以微乳为流动相的高效液相色谱法称为微乳液相色谱法（microemulsion liquid chromatography,MELC）。     

光学异构20（R）-人参皂苷Rg3微乳的相图研究

目的:筛选人参皂苷Rg3空白微乳处方组成.方法:通过滴定法绘制伪三元相图,以微乳区面积大小为指标,考察各系统的相图行为及各因素对微乳区形成的影响.结果:不同的表面活性剂、助表面活性剂、Km值、油相物质的种类、温度等对微乳形成均有较大影响.结论:Km=2,25℃时形成的曲拉通X-100/异丙醇/油酸乙酯/水微乳体系为最优的微乳体系.     

油酸微乳对利多卡因透皮吸收的影响

目的研究油酸微乳对利多卡因透皮吸收的影响。方法在制备相图的基础上，考察了微乳的组分对微乳形成的影响。选择适当的表面活性剂/助表面活性剂比例，制备利多卡因的油酸微乳处方，考察微乳、乳剂、胶束和饱和水溶液在透皮吸收方面的差异。结果以Labrasol为表面活性剂，吐温80为助表面活性剂所得油酸微乳的区域较大，微乳对利多卡因有明显的促透作用，透皮速率依次为微乳＞乳剂＞饱和水溶液＞胶束。结论油酸微乳可促进利多卡因的透皮吸收。     

鸦胆子油微乳的制备及稳定性研究

目的研究鸦胆子油微乳的制备、稳定性及微乳中药物含量的测定方法。方法选用MCT(辛葵酸甘油三脂)为油相,大豆卵磷脂为表面活性剂,乙醇为助表面活性剂,在制备三元相图的基础上,考察微乳的组分对微乳形成的影响。结果大豆卵磷脂为乳化剂形成微乳系统所需表面活性剂的量为20%～30%。结论采用微乳作为药物载体制备口服鸦胆子油微乳是一种很好的药物传递系统。     

头孢泊肟酯自乳化制剂的研究

目的 优化制备头孢泊肟酯自乳化最佳处方条件使其达到目标浓度50mg·g-1.方法 通过溶解度实验、相图绘制、以及形成乳剂的乳化程度、乳滴粒径大小,对头孢泊肟酯自乳化体系中的油相、表面活性荆、助表面活性剂进行筛选,寻找最佳处方条件.结果 优选的头孢泊肟酯自乳化制剂处方中油相为Lauroglycol FCC,表面活性剂为Labrasol,助表面活性荆为Labrafil M1944 CS.结论 初步成功地制备了头孢泊肟酯自乳化传递体系.     

索拉非尼自微乳化给药系统的制备及药物动力学研究(英文)

索拉非尼(Sorafenib)是一种新型抗肿瘤药物,但其在水中难溶,生物利用度低。为了增加索拉非尼的生物利用度,本研究制备了索拉非尼自微乳化给药系统,并以大鼠为实验动物测定了该给药系统的口服相对生物利用度。该给药系统以油酸乙酯(20%,w/w)为油相,聚氧乙烯蓖麻油(48%,w/w)为主要乳化剂,聚乙二醇400(16%,w/w)和乙醇(16%,w/w)为助乳化剂,索拉非尼的终浓度为20 mg/mL。该制剂自微乳化后粒径为20-25 nm。与索拉非尼混悬液相比,自微乳化给药系统可以显著增加索拉非尼的AUC,C_(max)和MRT,降低清除率,T_(max)没有明显变化。尤其是与口服混悬液相比,其相对生物利用度提高近25倍,说明索拉非尼自微乳化给药系统有望开发成为增加其口服吸收的药物制剂。     

Self-Nanoemulsifying Drug Delivery System of Lutein: Physicochemical Properties and Effect on Bioavailability of Warfarin

Objective of present study was to prepare and characterize self-nanoemulsifying drug delivery system (SNEDDS) of lutein and to evaluate its effect on bioavailability of warfarin. The SNEDDS was prepared using an oil, a surfactant, and co-surfactants with optimal composition based on pseudo-ternary phase diagram. Effect of the SNEDDS on the bioavailability of warfarin was performed using Sprague Dawley rats. Lutein was successfully formulated as SNEDDS for immediate self-emulsification and dissolution by using combination of Peceol as oil, Labrasol as surfactant, and Transcutol-HP or Lutrol-E400 as co-surfactant. Almost complete dissolution was achieved after 15 min while lutein was not detectable from the lutein powder or intra-capsule content of a commercial formulation. SNEDDS formulation of lutein affected bioavailability of warfarin, showing about 10% increase in C_max and AUC of the drug in rats while lutein as non-SNEDDS did not alter these parameters. Although exact mechanism is not yet elucidated, it appears that surfactant and co-surfactant used for SNEDDS formulation caused disturbance in the anatomy of small intestinal microvilli, leading to permeability change of the mucosal membrane. Based on this finding, it is suggested that drugs with narrow therapeutic range such as warfarin be administered with caution to avoid undesirable drug interaction due to large amount of surfactants contained in SNEDDS.     

维生素E烟酸酯自乳化制剂处方研究

目的研究维生素E烟酸酯(简称VEN)自乳化制剂,探求其最佳处方配比。方法通过溶解度实验、正交筛选和假三角相图的绘制,以形成自乳化区域的大小、溶出度和所得乳滴粒径的大小为指标,对VEN自乳化制剂中的油相、乳化剂及助乳化剂的组成、用量进行筛选,找出最佳的搭配和处方配比。结果在VEN自乳化制剂处方中,以油酸乙酯为油相,聚氧乙烯蓖麻油(EL20)为乳化剂,乙二醇单乙基醚(transcutol)为助乳化剂时,可以获得较好的乳化效果。结论VEN自乳化制剂的最佳处方比例为m(VEN)∶m(油酸乙酯)∶m(EL20)∶m(transcuto1)=1∶0.75∶1.35∶0.9。     

Effect of process and formulation variables on the preparation of parenteral paclitaxel-loaded biodegradable polymeric nanoparticles: A co-surfactant study

The purpose of this study was to evaluate the effect of process (homogenization speed and evaporation time) and formulation (aqueous/organic phase ratio, surfactant concentration, polymer type and concentration, and drug amount) variables on the preparation of paclitaxel-loaded biodegradable polymeric nanoparticles using modified solvent evaporation technique. Thereafter, a formulation was selected and subjected to evaluation of inclusion of a co-surfactant for further reduction of particle size. Particle size, encapsulation efficiency and in-vitro drug release kinetics were evaluated. It was observed that the inclusion of vitamin E TPGS (0.01%), Poloxamer 188 (0.5%) or Tween 80 (0.25%) reduced the particle size of nanoparticles to 230, 244 or 301 nm from 438 nm, respectively. Encapsulation efficiency increased for both vitamin E TPGS and Poloxamer 188 up to concentration at 0.010% and 0.25%, respectively, while this was not the case for Tween 80. Comparison of drug release kinetics demonstrated that drug release accelerated from paclitaxel-loaded biodegradable nanoparticles prepared with the inclusion of Tween 80 but was delayed for Poloxamer 188 and vitamin E TPGS. Thus, it was concluded that the particle size of the nanoparticles could be reduced further and the paclitaxel release kinetics could easily be adjusted by taking advantage by the inclusion of a co-surfactant.     

Preparation and evaluation of andrographolide-loaded microemulsion

Andrographolide has a low aqueous solubility and oral bioavailability, which limits its clinical application. Reform the dosage forms of andrographolide to improve its aqueous solubility and oral bioavailability. The formulation, characterisation, stability, anti-inflammatory effect, pharmacokinetics and oral toxicity of andrographolide-loaded microemulsion, were studied. An formulation of O/W microemulsion consisting of an oil phase of isopropyl myristate, a surfactant phase of Tween 80, a co-surfactant of alcohol, and water was found to be ideal, with mean droplet size of 15.9?nm, a high capacity of solubilisation for andrographolide (8.02?mg?mL^?1). Such an andrographolide-loaded microemulsion is stable by monitoring the time, temperature and gravity-dependent change, and has a much better anti-inflammatory effect and a higher biological availability than andrographolide tablets. Besides, it also shows a very low acute oral toxicity. The andrographolide-loaded microemulsion is a promising dosage form of andrographolide.     

亚甲蓝油包水微乳的制备及其淋巴示踪特性的考察

目的研究亚甲蓝油包水微乳的处方工艺,并对其淋巴示踪特性进行研究。方法助表面活性剂浓度法绘制伪三元相图,考察油相、表面活性剂、助表面活性剂及其浓度对微乳形成的影响,正交设计优化处方,透射电镜观察形态,激光散射法测定粒径。通过小鼠右后脚掌皮下注射,观察小鼠腘淋巴结、髂淋巴结及腹主动脉(右肾)淋巴结的蓝染情况。结果亚甲蓝微乳的最终处方为m(大豆油)∶m[Span80-Tween80(HLB=8)]∶m(Transcutol P)∶m(质量分数为5%的葡萄糖溶液)=54.0∶36.0∶5.4∶3.6,载药质量分数为1%。亚甲蓝微乳外观圆整而呈球状,平均粒径为74.11 nm,30 m in内可将小鼠三级淋巴结蓝染。结论亚甲蓝微乳是一种具有开发前景的淋巴示踪剂,可使示踪更加准确、有效。     

白藜芦醇纳米乳的制备

采用伪三元相图法筛选了o/w型白藜芦醇纳米乳处方中的油相、表面活性剂和助表面活性剂.所得优选处方组成为三乙酸甘油酯-聚氧乙烯蓖麻油EL-烷基葡萄糖苷-1,2-丙二醇-水(0.08∶0.07∶0.14∶0.11∶0.60).透射电镜观察表明制品外观圆整、均匀.纳米乳平均粒径为(9.2±1.6) nm,其中白藜芦醇含量为(647±1)μg/ml.     

Characterization and evaluation of self-nanoemulsifying sustained-release pellet formulation of ziprasidone with enhanced bioavailability and no food effect

The purpose of this work was to develop self-nanomulsifying drug delivery systems (SNEDDS) in sustained-release pellets of ziprasidone to enhance the oral bioavailability and overcome the food effect of ziprasidone. Preformulation studies including screening of excipients for solubility and pseudo-ternary phase diagrams suggested the suitability of Capmul MCM as oil phase, Labrasol as surfactant, and PEG 400 as co-surfactant for preparation of self-nanoemulsifying formulations. Preliminary composition of the SNEDDS formulations were selected from the pseudo-ternary phase diagrams. The prepared ziprasidone-SNEDDS formulations were characterized for self-emulsification time, effect of pH and robustness to dilution, droplet size analysis and zeta potential. The optimized ziprasidone-SNEDDS were used to prepare ziprasidone-SNEDDS sustained-release pellets via extrusion-spheronization method. The pellets were characterized for SEM, particle size, droplet size distribution and zeta potential. In vitro drug release studies indicated the ziprsidone-SNEDDS sustained-release pellets showed sustained release profiles with 90% released within 10?h. The ziprsidone-SNEDDS sustained-release pellets were administered to fasted and fed beagle dogs and their pharmacokinetics were compared to commercial formulation of Zeldox as a control. Pharmacokinetic studies in beagle dogs showed ziprasidone with prolonged actions and enhanced bioavailability with no food effect was achieved simultaneously in ziprsidone-SNEDDS sustained-release pellets compared with Zeldox in fed state. The results indicated a sustained release with prolonged actions of schizophrenia and bipolar disorder treatment.