W／O／W型甘草酸单胺盐口服复乳的处方设计及其理化特性研究

采用均匀设计，以乳剂的稳定性参数为考察指标，考察了初乳乳化剂、复乳乳化剂、乳化时间等因素对复乳稳定性的影响；筛选出Ｗ／Ｏ／Ｗ型甘草酸单胺盐口服复乳的优化处方和工艺，并对复乳的主要理化特性和物理稳定性进行了考察。     

W/O/W型复乳配方的优选及性质考察

目的优选W/O/W型复乳较佳的配方。方法在前期预实验的基础上筛选出油水相比例、乳化剂Ⅰ的用量、辅助乳化剂的种类与用量、稳定剂的用量、稳定剂Ⅱ的用量、内外渗透压等8个影响复乳配方质量的因素,以复乳产率和离心分离时间为指标,选用L18(2×37)表进行正交试验。同时考察优选配方所制复乳的理化性质和稳定性。结果 8个因素对复乳质量的影响大小依次为:D>G>F>B>E>H>A>C,其中辅助乳化剂和乳化剂Ⅱ的用量是主要的影响因素。结论按照优选的配方可以制备出性状较好的复乳,且所得复乳理化性质和稳定性均良好。     

外用O／W型乳剂基质的制备

本文论述了油、水两种不相溶的成分通过计算形成Ｏ／Ｗ型乳剂油相所需最适ＨＬＢ，选择相应的乳化剂，使制成稳定的外用Ｏ／Ｗ型砷剂。     

提高W/O/W复合型乳剂稳定性的研究进展

目的:了解提高W/O/W复合型乳剂稳定性的各种手段和方法。方法:查阅近几年国内外有关文献资料进行分析综述。结果:乳化剂、油相、制备工艺、内水相、稳定剂均是影响复乳稳定性的因素。结论:国内外学者采取了各种相应的稳定措施,以为复乳的应用开辟一个更广阔的空间。     

大分子乳化剂对复乳稳定性的影响及应用

综述了大分子乳化剂改善复乳稳定性的作用机制及其在复乳中的应用现状.复乳是复杂的液体分散体系,为热力学不稳定系统,易发生分层、絮凝和合并,通常加入单体乳化剂以提高其稳定性.近年来大分子乳化剂如生物聚合物、嵌段聚合物、高分子乳化剂因能较好地改善复乳稳定性,在复乳中得到广泛应用.     

自乳化复乳给药系统的制备

目的 筛选自乳化复乳处方并考察其制备工艺.方法 以伪三元相图、自复乳的显微结构和粒径为指标,考察内水相质量分数、亲水乳化剂的种类和用量以及高速分散强度对自乳化复乳处方的影响,并研究其稳定性.结果 内水相-油相-Span80-Cremophor EL比例为12.5:75:25:10,高速分散强度为12×103 r·min-1时所得自复乳的显微形态及抗稀释能力较好.结论 制备了由油包水及亲水乳化剂构成的自乳化复乳给药系统.     

W/O/W型甘草酸单铵盐口服复乳的药物释放研究

Ｗ／Ｏ／Ｗ型甘草酸单铵盐口服复乳的药物释放研究高晓黎，孙殿甲，邱洪卓（新疆医学院药学系，乌鲁木齐８３００５４；天山制药工业有限公司，乌鲁木齐８３００００）甘草酸及其盐有广泛的药理作用，并在临床上用于病毒性肝炎的治疗。甘草酸单铵盐易溶于热水，冷后成凝胶...     

乳化剂后加法制备O/W型乳膏基质及质量考察

目的 探讨乳化荆后加法对O／W型乳膏基质质量的影响。方法 用乳化剂分相加入法和乳化剂后加法分别制备O／W型乳膏基质．并对稳定性和释放度进行评价。结果 乳化剂后加法所制得的乳滴粒径小，分散均匀，质量稳定，释放度高。结论 本法可在生产中推广应用。     

复乳处方设计及其物理稳定性的初步研究

通过对油、乳化剂、稳定剂等辅料的选择,确定了理想的w/o/w复乳处方和制备工艺,测定了复乳的理化性质如显微结构、粒度分布、流变性和荷电性。物理稳定性预测说明:在复乳内外水相中加入大分子物质作稳定剂能有效地提高复乳的稳定性。     

艾塞那肽W/O/W复乳的处方工艺优化及性质考察

摘 要 目的：对艾塞那肽复乳的处方及工艺进行优化,并评价其体外主要性质,为研发其长效制剂奠定基础。方法: 以复乳产率及分离时间为综合评价指标,采用正交试验优化艾塞那肽复乳的处方及制备工艺。对其形态、粒径分布、稳定性、包埋率及体外释药特性进行考察。结果:最佳处方为：W1相与O相体积比为1∶〖KG-*2〗1.2,乳化剂Ⅰ在O相中的质量浓度为10%,泊洛沙姆407在W2相中的质量浓度为10%,W1/O初乳与W2相的质量比1:1。最佳工艺为：初乳搅拌速度为10 000 r·min^-1,初乳搅拌时间为10 min,复乳搅拌速度为2 500 r·min^-1,复乳搅拌时间为3 min。艾塞那肽复乳形态圆整,平均粒径为（46.3±2.6）μm,离心稳定性及黏度稳定性均较好,包埋率高达90%以上,体外释药符合Higuchi方程Y=13.793X+5.598(r=0.988 3),具有明显的缓释长效性。结论:艾塞那肽复乳处方及制备工艺简单,稳定性较好,具有明显的缓释性。     

W/O/W型薄荷油复乳的制备及其性质初步研究

目的制备薄荷油W/O/W型复乳,并对其性质进行初步研究。方法采用二步法制备薄荷油W/O/W型复乳,对其物理性质如:外观、显微形态、乳剂类型、粘度、表面张力、相变温度、物理稳定性等方面进行初步研究。结果薄荷油W/O/W型复乳外观呈白色、外相能被曙红指示液染色、室温下的粘度为15.2 mPa.S,表面张力为30×10-3N.m-1,相变温度为84℃。结论二步法制备薄荷油W/O/W型复乳物理稳定性较好。     

内水相添加氯化钠对W/O/W型复乳性质的影响

目的探讨在内水相中添加氯化钠(NaCl)对W/O/W型复乳性质的影响。方法在前期试验优选出较佳W/O/W复乳处方的基础上,以1 g/L NaCl水溶液代替处方中的纯化水作为内水相,采用二步乳化法制备复乳,从显微结构、粒径分布、稳定性等方面比较复乳性质的变化。结果在内水相中添加NaCl(1 g/L)时,复乳主要为B型结构,外观较圆整,液滴大小较均匀,且乳滴不易聚集成一团,大部分粒子粒径在20～40μm之间,稳定性良好。结论在内水相中添加NaCl(1 g/L),有助于优化W/O/W型复乳物理化学性质,提高其稳定性。     

A study of the stability of W/O/W multiple emulsions.

The stability of W/O/W emulsions has been studied in batch agitators. The surfactants suitable for W/O/W emulsions were screened and the factors affecting the emulsion stability were also studied. Results showed that polyamine E644 was an excellent emulsifier for W/O emulsions since the emulsion stabilized by it has not only good stability but also shows smaller swelling. The stability of the emulsion increases with increase in membrane viscosity and concentration of surfactant, but decreases with increase in concentration of the internal reagent in the internal phase and the carriers in the membrane. Raising the agitation speed and the time for preparing the W/O emulsion is beneficial to membrane stability due to formation of smaller internal droplets, but raising the speed for dispersing the W/O emulsion in the external phase results in an increase in membrane breakage.     

Slow release of chloroquine phosphate from multiple taste-masked W/O/W multiple emulsions

Abstract

The efficacy and safety of chloroquine as an antimalarial has contributed to the survival of millions in the past 50 years. Chloroquine is widely available, cheap, well tolerated and orally well absorbed. Therefore, it remains an important antimalarial drug. However, on oral administration, particularly to children, the unpleasant taste is a problem. This could be avoided by ‘taste-masked and controlled release’ formulations such as multiple emulsions. Although Plasmod-ium falciparum has developed resistance to many antimalarial drugs, including chloroquine, resistance may be attributed, among other factors, to subclinical dosage of chloroquine from administered pharmaceutical forms. This could also be relevant in the treatment of rheumatoid arthritis. Multiple W/O/W emulsions of chloroquine phosphate were prepared. Assessment of emulsion stability showed no significant change in the system. Prolonged storage (four months) of the emulsion resulted in negligible loss of chloroquine phosphate. The results suggest, therefore, that chloroquine phosphate releases due to diffusion of the drug from the internal globules and not as a consequence of instability of the W/O/W emulsion. These characteristics are in accordance with the requirements for controlled release Pharmaceuticals. Stability of multiple emulsions could have resulted from interfacial polymerization or complexion between molecules. Release assessments showed faster rates for W/O/W emulsions which had smaller internal aqueous globules and, therefore, an increased interfacial area. Furthermore, transport of high-diffusion coefficient micelles could have given a greater solute flux in these systems.     

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.     

An investigation into the characteristics and drug release properties of multiple W/O/W emulsion systems containing low concentration of lipophilic polymeric emulsifier

Multiple W/O/W emulsions with high content of inner phase (Phi1=Phi2=0.8) were prepared using relatively low concentrations of lipophilic polymeric primary emulsifier, PEG 30-dipolyhydroxystearate, and diclofenac diethylamine (DDA) as a model drug. The investigated formulations were characterized and their stability over the time was evaluated by dynamic and oscillatory rheological measurements, microscopic analysis and in vitro drug release study. In vitro release profiles of the selected model drug were evaluated in terms of the effective diffusion coefficients and flux of the released drug. The multiple emulsion samples exhibited good stability during the ageing time. Concentration of the lipophilic primary emulsifier markedly affected rheological behaviour as well as the droplet size and in vitro drug release kinetics of the investigated systems. The multiple emulsion systems with highest concentration (2.4%, w/w) of the primary emulsifier had the lowest droplet size and the highest apparent viscosity and highest elastic characteristics. Drug release data indicated predominately diffusional drug release mechanism with sustained and prolonged drug release accomplished with 2.4% (w/w) of lipophilic emulsifier employed.     

Preparation of stable W/O/W type multiple emulsion containing water-soluble drugs and in vitro evaluation of its drug-releasing properties]

The stable water-in-oil-in-water (W/O/W) multiple emulsion was prepared by a two-step procedure for emulsification using glyceryl tricaprylate (Panasate-800) as the oil phase. The water-soluble drugs such as cefadroxil, cephradine, 4-aminoantipyrine, and antipyrine were selected and entrapped separately in the inner aqueous phase of W/O/W multiple emulsion. In consideration of parenteral administration, pH 7.4 phosphate buffered saline was used in both inner and outer aqueous phases. Moreover, these multiple emulsions could be significantly stable for a month at room temperature by the addition of hydrophilic polymer like gelatin and of amino acid like lysine to the inner aqueous phase.     

Rosmarinus officinalis L. extract and some of its active ingredients as potential emulsion stabilizers: a new approach to the formation of multiple (W/O/W) emulsion

Nowadays, novel topical formulations loaded with natural functional actives are under intense investigations. Therefore, the aim of our study was to evaluate how the rosemary extract and some of its active ingredients [rosmarinic acid (RA), ursolic acid (UA) and oleanolic acid (OA)] affect technological characteristics of multiple emulsion. Formulation has been prepared by adding investigated solutions (10%) in water/oil/water (W/O/W) multiple emulsion consisting of different lipophilic phases: olive oil and liquid paraffin, with 0.5% emulsifying agent (complex of sodium polyacrylate and polysorbate 20) under constant stirring with mechanical stirrer at room temperature. The emulsion parameters were evaluated using centrifugation test, freeze–thaw cycle test, microscopical and texture analyses. Rosemary's triterpenic saponins UA and OA showed the highest emulsion stabilizing properties: they decreased CI from 3.26% to 10.23% (p?<?0.05). According to obtained interfacial tension data, the effect of rosemary active ingredients is not surfactant-like. Even though emulsifier itself at low concentration intends to form directly the multiple emulsion, the obtained results indicate that rosemary extract containing active ingredients does not only serve as functional cosmetic agent due to a number of biological activities, but also offer potential advantages as a stabilizer and an enhancer of W/O/W emulsions formation for dermopharmaceutical and cosmetic preparations.     

Study of the Breakup Under Shear of a New Thermally Reversible Water-in-Oil-in-Water (W/O/W) Multiple Emulsion

Purpose. Thickening of the external aqueous phase of W/O/W multiple emulsions is essential to increase the release under shear. However, it leads to globules bursting during fabrication. To reduce this problem, we have tested a novel thermally reversible hydrogel, EMP hydrogel. This way, the corresponding multiple emulsion (EMPME) would gel only at skin temperature, which may increase the active ingredient delivery when topically applied. Methods. Samples were sheared at different shear rates and temperatures (20, 30, and 35°C) with a controlled rheometer. A granulometric analysis was then performed with a laser diffraction granulometer, to assess the break up as a function of the shear rate at the three temperatures. Conductometric measurements (CDM 230 conductometer) provided the corresponding release curves. Results. As we expected, EMPME exhibited a thermally reversible behavior. Compared to a reference emulsion thickened by carbopol, this new thermo–sensitive multiple emulsion displayed higher break up and fraction released at 35°C. Conclusion. The first thermally reversible multiple emulsion has been developed in the present work. This one presents interesting advantages: (1) an easy fabrication process with a higher entrapment yield and (2) a higher fraction released at 35°C compared with the reference emulsion.