药用微乳应用概况与发展趋势*

微乳作为一种新型的药物载体,具有极大的发展潜力。现综述微乳的定义、形成机制、制备方法和特点,并系统综述了近年来微乳在口服、注射、经皮、眼部、鼻腔转运给药制剂等方面的应用概况,以及作为一种技术用于制备固体脂质纳米粒的应用概况,分析了近年来微乳在发展过程中存在的问题,进一步展望了微乳的发展趋势。     

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.     

表面活性剂在药物载体中的应用

表面活性剂分子具有不对称结构,在溶液中能形成胶束、微乳液、囊泡、液晶等多种分子有序缔合结构.文章综述了表面活性剂的缔合结构在药物载体中的应用情况.     

利多卡因微乳的制备及性质考察

<正>利多卡因是一种酰胺类局部麻醉药,局部麻醉药作用起效快,维持时间长,穿透性、扩散性也较强,可以用于皮肤穿刺性检查、皮肤外科手术以及激光美容等各种医疗手段所引起的皮肤浅表创伤性疼痛的麻醉。微乳是一种液-液分散体系,一般由油相、水相、表面活性剂和助表面活性剂组成的,微乳具有稳定性好、制备简单、粒径小、缓释和靶向     

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。     

微乳透皮给药载体的制备及透皮影响因素研究进展

目的:介绍微乳透皮给药载体的制备及透皮吸收的影响因素。方法:根据文献,综述了微乳的形成机制、透皮给药载体的作用、微乳的制备及其载体的透皮吸收影响因素等方面的内容。结果与结论:微乳的形成机制主要有混合膜理论和增溶理论;其透皮给药载体的作用包括促透皮作用和缓释及降低药物刺激性作用;可通过基于相图的自发乳化法、转相乳化法、相转变温度乳化法、机械法制备微乳;药物、水相、油相、表面活性剂和助表面活性剂、化学促渗剂等因素可影响微乳载体的透皮吸收。微乳透皮给药载体在制备时要考虑其透皮吸收的效能,从透皮影响因素等方面综合考察,使其发挥透皮给药的独特优势。     

微乳在不同给药途径中的应用

微乳是一种热力学稳定的液-液分散体系，主要由水相、油相、表面活性剂和助表面活性剂4部分组成。微乳的形成是自发过程，只要各部分的组成合适，即可形成均匀透明或微呈乳光的液体。微乳粒径均匀，一般在10～100nm范围，根据结构可分为水包油型（O／W），油包水型（W／O）及双连续型。作为药物载体，微乳给药体系近年来已得到广泛研究与应用。通常来说，O／W型微乳可以增加亲脂性药物的溶解度，W／O型则可延长水溶性药物的释放时间，起到缓释作用。微乳还可对难溶性药物起增溶作用，以制成复方制剂。微乳粒径小，可采用过滤灭菌；热力学稳定，则易于制备和保存。微乳作为药物载体，还具有低黏度、吸收迅速、靶向释药的特点，并可提高药物的生物利用度，降低毒副作用。下面主要从口服、注射、经皮、眼部、鼻腔、齿根、胃内灌注等给药途径综述微乳在药物传递体系中的应用。     

固体自微乳载体、固体化方法及稳定性研究进展

目的：对国内外近年来固体自微乳的载体、固体化方法及稳定性的研究进展进行综述,为该剂型的进一步研究和开发提供参考。方法：搜集国内外相关文献进行综合分析。结果：新型的载体材料和新的固体化方法可进一步提高固体自微乳的自乳化性能、药物的分散度,提高难溶性药物的溶出度和生物利用度,还可以改善药物的稳定性。结论：固体自微乳制剂具有微乳和固体制剂的双重优势,是非常具有研发前景的新型固体制剂,随着新型载体材料和固体化方法的开发,该剂型将得到广泛的应用。     

固体自微乳药物递送系统的研究进展

作为一种新型的药物递送系统,固体自微乳药物递送系统可以显著提高水难溶性药物的口服生物利用度,且具有液态自微乳和固体制剂二者的优势。通过设计不同的辅料处方和包衣技术,可以控制药物释放使其具有靶向性,来达到不同的给药目的。固体自微乳药物递送系统的应用前景广阔,具有研究意义。本文对固体自微乳载体、固化技术、固体自微乳新制剂的应用进行了总结归纳,为提高水难溶性药物释放的固体自微乳化技术的研究提供了参考。     

Evaluation of microemulsion and liposomes as carriers for oral delivery of transforming growth factor alpha in rats

The aim of the present study is to develop microemulsion and liposome carrier systems for oral administration of transforming growth factor alpha (TGF-α) and to investigate the effects of these carrier systems on the gastrointestinal efficiency in rats. Microemulsion (w/o) and liposomes (MLV) were developed and characterised. The carrier systems were administered intragastrically by gastric cannula to male Wistar rats. The highest reduction in the basal acid secretion was observed in the microemulsion containing TGF-α and aprotinin group (TAME).The gastric mucus secretion in microemulsion containing TGF-α (TME) and TAME treatment groups increased significantly compared to the other groups. TGF-α levels in both stomach and duodenum were significantly increased in the TAME group. As a result, it was determined through confocal laser scanning microscope (CLSM) studies that exogenous-applied TGF-α attached to endogenous EGF receptors. The microemulsion formulation was found to be a more suitable carrier system for oral administration of TGF-α.     

Bicontinuous sucrose ester microemulsion: a new vehicle for topical delivery of niflumic acid

The bicontinuous sucrose ester based microemulsion microstructure was characterised by a freeze fracture electron micrograph (FFEM) technique. The relationship between the microstructure and the efficacy of the microemulsion (ME) as a drug carrier system was investigated. The bioavailability of niflumic acid, a potent anti-inflammatory drug, incorporated at different concentrations in the microemulsion vehicle was investigated in vivo and compared with Nifluril® ointment (3%), a commercially available form. The methyl nicotinate model was used to induce inflammation. Following topical application of methyl nicotinate, various niflumic acid forms were immediately applied to the skin. The vascular response to methyl nicotinate on the treated areas was monitored by a Laser Doppler Flowmetry technique. The results exhibit the performance of the microemulsion vehicle as a niflumic acid carrier compared to the marketed form. The 1% niflumic acid microemulsion is as efficient as the 3% niflumic acid ointment.     

Improved drug delivery using microemulsions: rationale, recent progress, and new horizons

Microemulsions are excellent candidates as potential drug delivery systems because of their improved drug solubilization, long shelf life, and ease of preparation and administration. The formulation of microemulsions for pharmaceutical use requires a thorough understanding of the properties, uses, and limitations of microemulsions. Three distinct microemulsions--oil external, water external, and middle phase--can be used for drug delivery, depending upon the type of drug and the site of action. In this article, we present an examination of microemulsions as drug carrier systems, starting with general information and moving to a thorough review of the microemulsion literature, with a special section devoted to microemulsion-based gels.     

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。     

A propofol microemulsion with low free propofol in the aqueous phase: Formulation, physicochemical characterization, stability and pharmacokinetics

The purpose of this study was to develop a propofol microemulsion with a low concentration of free propofol in the aqueous phase. Propofol microemulsions were prepared based on single-factor experiments and orthogonal design. The optimal microemulsion was evaluated for pH, osmolarity, particle size, zeta potential, morphology, free propofol in the aqueous phase, stability, and pharmacokinetics in beagle dogs, and comparisons made with the commercial emulsion, Diprivan(?). The pH and osmolarity of the microemulsion were similar to those of Diprivan(?). The average particle size was 22.6±0.2nm, and TEM imaging indicated that the microemulsion particles were spherical in appearance. The concentration of free propofol in the microemulsion was 21.3% lower than that of Diprivan(?). Storage stability tests suggested that the microemulsion was stable long-term under room temperature conditions. The pharmacokinetic profile for the microemulsion showed rapid distribution and elimination compared to Diprivan(?). We conclude that the prepared microemulsion may be clinically useful as a potential carrier for propofol delivery.     

水杨酸微乳的制备及质量评价

目的制备水杨酸微乳并进行质量评价。方法采用吐温-80作乳化剂,肉豆蔻异丙酯为油相,借助伪三元相图的研究手段确定乳化剂和助乳化剂的最佳配比,制成不同浓度的水杨酸微乳,并从含量测定、透光率、pH值、比重、黏度测定和稳定性方面进行了评价。结果吐温-80与1,2-丙二醇的配比为15：1,其微乳区最大,几种浓度的水杨酸制剂均能形成微乳且稳定分散于制剂中。结论微乳能增加水杨酸在制剂中的溶解度,方便于临床应用和提高了治疗效果。