微乳及其在不同给药途径中的应用

<正>制备新颖和有效的给药载体,促进药物吸收进入体循环,是当前新药开发的重要研究方向,将药物包埋在微粒中给药的方法即是其中之一。该方法包括微囊、微球、纳米微球等,其中脂质体、乳剂、复乳、微乳等液体给药载体的发展非常迅速,其能够减少药物在体内、外的降解,控制其释放甚至实现靶向给药[1]。本文针对微乳结构、特点及其在不同给药途径中的应用进行综述。     

天然药物靶向给药系统的研究

采用新型药物载体使天然药物具有靶向作用是近年来药剂学的研究热点之一。综述脂质体、纳米粒、微球、微乳、药质体等新型载体在天然药物靶向给药系统研究中的应用,并介绍膜融合脂质体、纳米脂质载体、药脂结合物纳米粒以及分泌颗粒类似物等几种新型靶向给药系统的药物载体。     

不同纳米药物载体临床应用研究进展

目的 为不同纳米药物载体的临床应用提供参考。方法 查阅国内外相关文献,总结纳米药物载体类型及其适宜运载的药物类型。结果 常见的纳米药物载体类型包括纳米脂质体、微球、微囊、纳米乳和亚微乳等。纳米脂质体适宜运载紫杉醇及青蒿素类等水溶性较差的药物;微球适宜运载半衰期较短的局部麻醉药物和部分化学药物治疗药物,以降低其释放速率;微囊可固体化某些运输、应用和贮存不便的液体药物,并能减少和避免复方制剂中产生的配伍禁忌;纳米乳已被广泛应用于注射剂、口服剂、经皮贴剂和滴眼剂等,可提高难溶性药物的生物利用度;胃肠外给药常以亚微乳为载体,可提高药物的稳定性,大幅增加其在体内及经皮吸收量,并降低药物毒副作用。结论 结合不同类型纳米药物载体的特性与药物自身性质和给药途径,可避免传统剂型的弊端,提高临床疗效。     

微乳凝胶经皮给药制剂的研究与应用进展

目的 介绍微乳凝胶经皮给药制剂的研究与应用进展。方法 根据近年来国内外相关文献,对微乳凝胶作为经皮给药载体的处方筛选、制备、体外释药性能、质量检查、研究应用进展等方面进行介绍。结果 微乳凝胶具有显著增强药物的经皮渗透能力、降低药物刺激性和延缓药物释放等作用,且更便于给药。结论 微乳凝胶有望成为一种具有重要应用价值的经皮给药新剂型。     

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。     

纳米给药系统在难溶性药物制剂研究中的应用

近年来,难溶性药物给药系统一直是制剂学研究的重点和难点之一。纳米载体由于其良好的生物相容性及可装载大量难溶性药物等特点而被广泛应用于难溶性药物给药系统的研究,该类载体主要包括纳米粒、脂质体、纳米乳、聚合物胶束、纳米混悬剂等。本文结合近几年国内外文献报道,对纳米给药系统在难溶性药物制剂研究中的最新进展进行概述。     

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。     

我国微乳技术在药学领域中的研究进展

微乳是由油相、水相、乳化剂及助乳化剂在适当比例自发形成的一种透明或半透明、低黏度、各向同性且热力学稳定的油水混合系统,其作为药物载体的主要优点是可同时增溶不同溶解性能的成分,分散性好,利于吸收,提高生物利用度.现从微乳作为给药载体时不同类型配方、质量评价方法、各种微乳给药系统的优势,以及微乳在药学领域的其他应用情况等方面,对近年来国内进展状况进行综述,并对微乳在中药方面的应用提出建议.     

经皮给药系统中新型载体的应用

摘 要经皮给药相比于传统的口服给药和注射给药,有着使用方便、药物局部浓度高、安全性强的特点。本文综述了近几年国内外文献报道的有关经皮给药系统中,可以增加药物经皮转运效率的新型载体（微乳、醇质体、传递体、囊泡、前体脂质体、凝胶等）的组成、特点及应用。这些新型的经皮给药载体所呈现出来的优越性,使其具有良好的研究价值和广阔的发展空间。     

纳米乳与亚微乳给药系统(续)

4亚微乳的制备和影响因素 亚微乳常作为给药的载体,其特点包括:提高药物稳定性、降低毒副作用、提高体内及经皮吸收率、使药物具有靶向性.     

Multiple emulsions: an overview

Multiple emulsions are complex polydispersed systems where both oil in water and water in oil emulsion exists simultaneously which are stabilized by lipophillic and hydrophilic surfactants respectively. The ratio of these surfactants is important in achieving stable multiple emulsions. Among water-in-oil-in-water (w/o/w) and oil-in-water-in-oil (o/w/o) type multiple emulsions, the former has wider areas of application and hence are studied in great detail. Formulation, preparation techniques and in vitro characterization methods for multiple emulsions are reviewed. Various factors affecting the stability of multiple emulsions and the stabilization approaches with specific reference to w/o/w type multiple emulsions are discussed in detail. Favorable drug release mechanisms and/or rate along with in vivo fate of multiple emulsions make them a versatile carrier. It finds wide range of applications in controlled or sustained drug delivery, targeted delivery, taste masking, bioavailability enhancement, enzyme immobilization, etc. Multiple emulsions have also been employed as intermediate step in the microencapsulation process and are the systems of increasing interest for the oral delivery of hydrophilic drugs, which are unstable in gastrointestinal tract like proteins and peptides. With the advancement in techniques for preparation, stabilization and rheological characterization of multiple emulsions, it will be able to provide a novel carrier system for drugs, cosmetics and pharmaceutical agents. In this review, emphasis is laid down on formulation, stabilization techniques and potential applications of multiple emulsion system.     

Development of novel flurbiprofen-loaded solid self-microemulsifying drug delivery system using gelatin as solid carrier

To develop a novel flurbiprofen-loaded solid self-microemulsifying drug delivery system (solid SMEDDS) with improved oral bioavailability using gelatin as a solid carrier, the solid SMEDDS formulation was prepared by spray-drying the solutions containing liquid SMEDDS and gelatin. The liquid SMEDDS, composed of Labrafil M 1944 CS/Labrasol/Transcutol HP (12.5/80/7.5%) with 2% w/v flurbiprofen, gave a z-average diameter of about 100?nm. The flurbiprofen-loaded solid SMEDDS formulation gave a larger emulsion droplet size compared to liquid SMEDDS. Unlike conventional solid SMEDDS, it produced a kind of microcapsule in which liquid SMEDDS was not absorbed onto the surfaces of carrier but formed together with carrier in it. However, the drug was in an amorphous state in it like conventional solid SMEDDS. It greatly improved the oral bioavailability of flurbiprofen in rats. Thus, gelatin could be used as a carrier in the development of solid SMEDDS with improved oral bioavailability of poorly water-soluble drug.     

Releasing properties of water soluble drug in internal water phase of W/O/W multiple emulsions]

A stable water/liquid paraffin system water-in-oil-in-water (W/O/W) multiple emulsion was prepared by the two-step procedure of emulsification using a variety of nonionic emulsifying agents, such as Span 80 and Tween 20. After comparison of the releasing properties of such water soluble drugs as cefadroxil, cephradine, 4-aminoantipyrine and antipyrine which were entrapped separately in the inner aqueous phase of the W/O/W multiple emulsion, a large difference was observed. It was ascertained that the difference in these releasing properties was due to no physical rupture by the microscopic observation and the results of the release test of W/O/W multiple emulsion with two kinds of drugs entrapped simultaneously in an inner aqueous phase. This reason was presumed to be dependent on permeation in the oily phase of the drug itself. It was proved that the differences of releasing properties tended to depend on the molecular weight and were closely related to the drug concentration of outer aqueous phase of W/O/W multiple emulsion containing the drug in both aqueous phases prepared as an experimental model. Therefore, two possible mechanisms for the releasing of drugs in W/O/W multiple emulsion may be interpreted as follows: the first is that the mixed and inversed micelles formed by Span 80 and Tween 20 agents in the oily phase act as a carrier of drugs, and the second is that drug molecules diffuse through small pore existing in very thin lamella of the emulsifying agents partially formed in the oil layer owing to the fluctuation of the thickness.     

蓝萼甲素固体脂质纳米粒的制备工艺研究

目的以固体脂质纳米粒作为蓝萼甲素新型缓释给药系统,进行蓝萼甲素固体脂质纳米粒的制备工艺研究。方法采用乳化蒸发-低温固化法,均匀设计优化处方,按照优化工艺条件,以硬脂酸作为蓝萼甲素模型药物载体,制备得到蓝萼甲素固体脂质纳米粒,并对其包封率进行考察。结果本研究制得的蓝萼甲素固体脂质纳米粒的包封率达到80.4%。结论本研究方法可以作为蓝萼甲素固体脂质纳米粒的制备方法。     

高分子聚合物PLGE超声微泡的制备与体外显影研究

目的：应用新型高分子聚合材料聚乳酸/羟基乙酸/聚乙二醇嵌段共聚物（PLGE）制备超声微泡并观察其体外显影效果。方法：采用复乳法（W/O/W）制备超声微泡,使用光镜和扫描电镜观察形态、测定微泡的粒径分布,通过体外溶液超声显影实验观察显影效果。结果：采用该法制备的超声微泡呈球形,粒径分布均匀,平均粒径1.75μm,体外显影效果好。结论：以PLGE为外壳材料,采用复乳法制备的微泡可以作为超声造影剂,为下一步载药研究提供基础。     

依托泊甙复乳处方设计和稳定性考核

通过对油的品种、乳化剂及 HLB 值、稳定剂等辅料的筛选,并经正交设计试验获得较稳定的 W_1o/w_2型依托泊甙复乳处方和制备工艺条件,测定了药物包裹率并考核了稳定性。     

Comparison of solid self-microemulsifying drug delivery system (solid SMEDDS) prepared with hydrophilic and hydrophobic solid carrier

In order to compare the effects of hydrophilic and hydrophobic solid carrier on the formation of solid self-microemulsifying drug delivery system (SMEDDS), two solid SMEDDS formulations were prepared by spray-drying the solutions containing liquid SMEDDS and solid carriers. Colloidal silica and dextran were used as a hydrophobic and a hydrophilic carrier, respectively. The liquid SMEDDS, composed of Labrafil M 1944 CS/Labrasol/Trasncutol HP (12.5/80/7.5%) with 2% w/v flurbiprofen, gave a z-average diameter of about 100 nm. Colloidal silica produced an excellent conventional solid SMEDDS in which the liquid SMEDDS was absorbed onto its surfaces. It gave a microemulsion droplet size similar to that of the liquid SMEDDS (about 100 nm) which was smaller than the other solid SMEDDS formulation. In the solid SMEDDS prepared with dextran, liquid SMEDDS was not absorbed onto the surfaces of carrier but formed a kind of nano-sized microcapsule with carrier. However, the drug was in an amorphous state in two solid SMEDDS formulations. Similarly, they greatly improved the dissolution rate and oral bioavailability of flurbiprofen in rats due to the fast spontaneous emulsion formation and the decreased droplet size. Thus, except appearance, hydrophilic carrier (dextran) and hydrophobic carrier (colloidal silica) hardly affected the formation of solid SMEDDS such as crystalline properties, dissolution and oral bioavailability.     

口服干乳剂研究进展

干乳剂是新型的药物载体传递系统，理化稳定性好，再分散性好，能显著改善难溶性药物的溶出，增加体外释放，促进肠吸收，提高口服生物利用度。对近年来国外文献以喷雾干燥法制备干乳剂的最新研究进展，该文做了主要概述，表明喷雾干燥乳剂作为一种含油的粉末制剂，其应用前景广阔。     

Release of antiseptics from the aqueous compartments of a w/o/w multiple emulsion

A w/o/w multiple emulsion drug carrier system has been developed for local vaginal therapy. To improve its efficacy and to extend the antimicrobial spectrum activity of benzalkonium chloride (CBZ), which is introduced in the external aqueous phase, chlorhexidine digluconate (CHD) was added to the internal aqueous phase of the multiple emulsions. The minimal bactericidal concentrations (MBC) for the association of CHD and CBZ in emulsion were determined towards Escherichia coli and Staphylococcus aureus. The main release mechanism considered for the CHD encapsulated in the inner phase was a swelling-breakdown phenomenon which followed dilution of the emulsion under hypo-osmotic conditions. In order to demonstrate this release, the bactericidal effect of multiple emulsions undiluted and diluted 1-5 and 1-10 in hypo-osmotic conditions at two CHD concentrations was evaluated. To validate and quantify this release, rheological and release kinetics studies were used. The bactericidal activity of combination CBZ-CHD in the emulsion was synergistic on the two bacterial strains and the release of encapsulated CHD in the internal phase was obtained following its dilution in hypo-osmotic conditions. Vaginal administration could be carried out following dilution at 1-5 in sterile water for multiple emulsions containing the lower concentration of CHD.     

Development of drug delivery systems for the dermal application of therapeutic DNAzymes

DNAzymes are potent novel drugs for the treatment of inflammatory diseases such as atopic dermatitis. DNAzymes represent a novel class of pharmaceuticals that fulfil a causal therapy by interruption of the inflammation cascade at its origin. There are two challenges regarding the dermal application of DNAzymes: the large molecular weight and the sensitivity to DNases as part of the natural skin flora. To overcome these limitations suitable carrier systems have to be considered. Nano-sized drug carrier systems (submicron emulsions, microemulsions) are known to improve the skin uptake of drugs due to their ability to interact with the skin's lipids. To protect the drug against degradation, the hydrophilic drug may be incorporated into the inner aqueous phase of carrier systems, such as water-in-oil-in-water multiple emulsions. In the present study various emulsions of pharmaceutical grade were produced. Their physicochemical properties were determined and the influence of preservation systems on stability was tested. Drug release and skin uptake studies using various skin conditions and experimental set-ups were conducted. Furthermore, cellular uptake was determined by flow cytometric analysis. The investigations revealed that the developed multiple emulsion is a suitable and promising drug carrier system for the topical application of DNAzyme.