紫杉醇静脉注射脂肪乳配方及制备工艺的考察

考察三种紫杉醇脂肪乳配方的时间及温度稳定性、制备工艺对其粒径的影响以及测定脂肪乳中紫杉醇的浓度,光子相关光谱法(PCS)测试结果表明,以单一F-68作为乳化剂的脂肪乳粒径为235±15nm,PDI为0.2±0.1,Zeta电位为-35±10mV,在室温(25℃)下放置60d粒径变化不明显,较含有92%、98%蛋黄卵磷脂的脂肪乳稳定;随着高压均质压力升高,脂肪乳的粒径减小,高压均质循环次数对粒径几乎无影响;4000r/min条件下离心15min不分层,说明脂肪乳具有良好的离心稳定性。高效液相色谱(HPLC)结果表明,脂肪乳中紫杉醇的浓度为0.291mg/mL,提高初始加入量后浓度可达0.673mg/mL。     

介质弹性对多重乳液分散度的影响

多重乳液的单分散性是与粒径相关的一些重要性质如乳液稳定性、乳化剂界面分配等研究工作的基础.在保证连续相与分散相的粘度比∈(0.1,1)条件下,分别以聚丙烯酰胺及甘油为连续相,以不同内相体积w1/o一级乳液为分散相,在相应流变性质研究的基础上,研究了介质的弹性对多重乳液分散度的影响,制备了分散度20%左右的拟单分散多重乳液体系.研究表明,连续相的弹性是制备拟单分散多重乳液的必要条件,分散相的弹性有利于单分散多重乳液的制备.完善了前人的相关研究结果.     

硫辛酸脂质纳米粒的制备工艺研究

研究了负载硫辛酸纳米乳液的高温相行为,获得其高温相图。根据相图结果,采用高压均质法制备了硫辛酸脂质纳米粒。系统研究了乳化剂配比、均质循环次数等实验参数对脂质纳米粒制备的影响,进而优化了制备条件,并通过了优化配方重复性试验的验证。光子相关谱结果表明,硫辛酸脂质纳米粒的平均粒径为214＋59nm。时间和温度稳定性测试表明,硫辛酸脂质纳米粒在两个月内具有良好的稳定性。     

聚碳酸亚丙酯乳液的制备与性能

采用直接乳化法制备聚碳酸亚丙酯(PPC)乳液,研究乳化剂亲水亲油平衡(HLB)值、连续相聚乙烯醇(PVA)浓度对乳液性能的影响。研究表明,当乳化剂HLB值在12.6~16.0之间时,均可制得PPC乳液。PVA质量分数高于1%则会导致PPC乳液稳定性下降。当乳化剂HLB值为13.0时,乳液白色泛蓝光,电导率为96.2μS/cm,固含量为3.73%,5000r/min下离心10min既无沉淀也无分层产生,静置半月无明显变化,粒径分布曲线分别在2μm和30μm处有2个独立的峰。     

负载辅酶Q10的纳米结构脂质载体的制备及理化性质研究

运用高压均质法制备出负载辅酶Q1（0CoQ10）的纳米结构脂质载体（NLC）,利用光子相关光谱（PCS）测得在常温下的平均粒径为108±10nm,多分散性指数（PI）在0.2-0.6之间;Zeta电位是-28±5mV;随着负载量的增加,NLC的粒径明显增大,高压均质的次数增多,NLC的粒径减小。利用pH计测得样品的pH接近于7.0。从温度和时间稳定性、离心稳定性两个方面对CoQ10-NLC的物理稳定性进行研究,测得在常温下避光保存的CoQ10-NLC的粒径变化较小,低温下易凝聚沉淀;在10000r/min的转速下离心制备得到的NLC分散液25min不分层。最后运用反相高效液相色谱法测得CoQ10-NLC的含量4.709g·mL^-1。     

两相真空高压均质机制备丝素蛋白包埋O/W乳液及其稳定性

通过两相真空高压均质机制备了丝素蛋白包埋的玉米油乳液.pH＝7时,对不同丝素蛋白浓度(0.2%～3%(质量分数))包埋的玉米油(10%(质量分数))乳液表面电位、粒径大小及表面形貌进行了表征,确定了最佳丝素蛋白用量为1%(质量分数),在此最佳用量下,乳液表面电荷为-28.1mV,粒径d43为5.18μm.此外,研究了pH＝2～8对乳液体系物理稳定性的影响,环境pH＝2、3、6、7、8时,乳液十分稳定;pH＝4、5时,乳液不稳定,这是由于该pH值靠近丝素蛋白等电点,表面电荷趋于0mV,乳液液滴间缺乏静电排斥而形成凝集.结果表明,采用两相高压均质机可制备丝素蛋白包埋的玉米油乳液.     

液体石蜡乳液制备及其性能研究

利用高速搅拌和超声乳化法,制备了液体石蜡乳液。研究了表面活性剂的组成、用量和温度等因素对乳液性能的影响。结果表明:添加0.5%的油酸钠和十六烷基三甲基溴化铵混合表面活性剂制备的乳液为O/W型,乳液久置不分层,稀释分散性为一级,无漂油现象,稳定性良好。乳液的表面张力平均值为24.50mN/m,D50平均粒径为1.56μm。     

纳米纤维素凝胶微粒及其在Pickering泡沫中的应用

目的研究氧化纳米纤维素/乳酸链球菌素(TONCC/nisin)凝胶粒子的性质及其在环保抗菌泡沫中的应用。方法利用TONCC的表面羧基基团与nisin的表面阳离子的吸附耦合作用,制备TONCC/nisin水凝胶和微凝胶,以微凝胶作为稳定粒子,环氧大豆油丙烯酸酯(AESO)为油相,制备TONCC/nisin/AESO Pickering乳液,对水凝胶、微凝胶、乳液的稳定性进行研究;通过热固化乳液得到环保抗菌的泡沫材料,并对泡沫材料的结构和抗菌效果进行表征。结果水凝胶的结构随着在水中浸泡时长的增加而发生变化,宏观表现为坍塌变形,nisin逐渐析出,微凝胶随着静置时间的延长其粒径变化不大;以微凝胶作为界面稳定剂的AESO乳液的热稳定性较好,在90℃下加热30 min乳液液滴并未发生聚并现象,该乳液固化后形成的多孔泡沫材料对李斯特菌的抑制作用明显,当泡沫中nisin含量为2μg/g时,其抑菌率为43%。结论TONCC和nisin形成的微凝胶粒子在水中稳定性较好,可以用于乳化AESO制备Pickering泡沫,同时赋予泡沫多孔性和抗菌性,在制备环保抗菌泡沫方面有很大的应用潜力。     

W/O/W复乳体系制备聚合物微胶囊的影响因素分析

总结了近年来W/O/W复乳体系制备微胶囊和提高W/O/W型复乳液稳定性的研究进展,重点分析了W/O/W复乳体系制备聚合物微胶囊的影响因素,主要有W/O初乳的稳定性,壁材,外水相,复乳的乳化条件和囊壁固化条件。对微胶囊形貌的改善、包覆率的提高及粒径分布的控制将起到积极作用。     

凸棒颗粒稳定的橄榄油／水型Pickering乳状液的制备条件及形成机理研究

选取凹凸棒作为乳化剂,系统研究pH、颗粒浓度、油相体积分数以及不同价态盐对橄榄油／水型Pickering乳状液稳定性的影响,结果表明,体系pH在4～9范围内可制备出稳定的乳状液;颗粒浓度的提高可增强乳液的分层和聚结稳定性;乳液液滴直径随油相体积分数的增加先增大后减小;无机盐的引入不会对乳液相及水相的体积产生影响,但对乳液液滴的尺寸分布影响显著,其中NaCl浓度的增加有利于乳状液液滴数均直径的增加,而CaCl2浓度增加时,乳状液液滴数均直径呈现先增大后减小的变化趋势。研究表明,凹凸棒可作为一种新型纳米乳化剂应用于绿色乳状液的制备。     

“Vitamin E” fortified parenteral lipid emulsions: Plackett–Burman screening of primary process and composition parameters

The objective of this study was to screen the effect of eight formulations and process parameters on the physical attributes and stability of “Vitamin E”-rich parenteral lipid emulsions. Screening was performed using a 12-run, 8-factor, 2-level Plackett–Burman design. This design was employed to construct polynomial equations that identified the magnitude and direction of the linear effect of homogenization pressure, number of homogenization cycles, primary and secondary emulsifiers, pre-homogenization temperature, oil loading, and ratio of vitamin E to medium-chain triglycerides (MCT) in the oil phase on particle size, polydispersity index, short-term stability, and outlet temperature of manufactured emulsions. The viscosity of vitamin E was reduced from 3700 (100%) to 64 mPa.s (30%) by MCT addition. As viscosity is critical for efficient emulsification, vitamin/MCT ratio was the most significant contributor for the stability of emulsions. Particle size increased from 236 to 388 nm, and percentage vitamin remaining emulsified after 48 h dropped from 100 to 73% with increase in vitamin/MCT ratio from 30/70 to 70/30. Significant decrease in particle size and PI, and an increase in outlet temperature were also observed with increase in homogenization pressure and number of homogenization cycles. Emulsifiers and oil loading, however, had insignificant effect on the responses. Overall, stable submicron emulsions at vitamin/MCT ratio of 30/70 could be prepared at 25,000 psi and 25 cycles in ambient conditions. The identification of these parameters by a well-constructed design demonstrated the utility of screening studies in the “Quality by Design” approach to pharmaceutical product development.     

Development of industrially feasible concentrated 30% and 40% nanoemulsions for intravenous drug delivery

Emulsions for parenteral nutrition loaded with drugs are used for optimized drug delivery, but in case of poorly oil soluble drugs, the injection volume can be too large when using commercial 10–20% oil emulsions. To reduce the injection volume, the feasibility of producing injectable, physically stable concentrated emulsions up to 40% oil content was investigated. Emulsions were made from fish oil, stabilized with egg lecithin, using high-pressure homogenization. Emulsions with oil contents of 10%–40% were investigated to assess basic correlations between increasing oil content, applied production pressures, homogenization cycles and resulting bulk droplet size, content of larger particles, zeta potential, viscosity and short-term stability. The observed correlations showed that in high-pressure homogenization, the contribution of the dispersive effect dominated the coalescence effect at low and Optimum production conditions for 30% and 40% nanoemulsions, i.e. 800 bar and 2 -3 homogenization cycles, were established on lab scale. These production conditions are industrially feasible. The obtained droplet sizes (about 200?nm) and the content of larger droplets were comparable to 10% commercial emulsions of parenteral nutrition, being important for in vivo tolerability and organ distribution. Despite the high oil concentration, the viscosity of the nanoemulsions was sufficiently low for injection. The short-term storage study showed physical stability for 1 month. A concentrated nanoemulsion base formulation from regulatory accepted excipients is now available, ready for loading with drugs.     

Development of industrially feasible concentrated 30% and 40% nanoemulsions for intravenous drug delivery

Emulsions for parenteral nutrition loaded with drugs are used for optimized drug delivery, but in case of poorly oil soluble drugs, the injection volume can be too large when using commercial 10-20% oil emulsions. To reduce the injection volume, the feasibility of producing injectable, physically stable concentrated emulsions up to 40% oil content was investigated. Emulsions were made from fish oil, stabilized with egg lecithin, using high-pressure homogenization. Emulsions with oil contents of 10%-40% were investigated to assess basic correlations between increasing oil content, applied production pressures, homogenization cycles and resulting bulk droplet size, content of larger particles, zeta potential, viscosity and short-term stability. The observed correlations showed that in high-pressure homogenization, the contribution of the dispersive effect dominated the coalescence effect at low and Optimum production conditions for 30% and 40% nanoemulsions, i.e. 800 bar and 2 -3 homogenization cycles, were established on lab scale. These production conditions are industrially feasible. The obtained droplet sizes (about 200?nm) and the content of larger droplets were comparable to 10% commercial emulsions of parenteral nutrition, being important for in vivo tolerability and organ distribution. Despite the high oil concentration, the viscosity of the nanoemulsions was sufficiently low for injection. The short-term storage study showed physical stability for 1 month. A concentrated nanoemulsion base formulation from regulatory accepted excipients is now available, ready for loading with drugs.     

Preparation and Evaluation of 2-(Allylthio)Pyrazine-Loaded Lipid Emulsion with Enhanced Stability and Liver Targeting

To develop 2-(allylthio)pyrazine (2-AP)-loaded lipid emulsion for parenteral administration, various lipid emulsions were prepared with soybean oil, lecithin, and other carriers using homogenization method, and their physical stabilities were investigated by measuring their droplet sizes. The pharmacokinetics and tissue distribution of 2-AP in lipid emulsion after intravenous administration to rats were evaluated compared with 2-AP in solution. 2-AP was lipophilic, sparingly water-soluble, and unstable in aqueous medium. The 2-AP-loaded lipid emulsion composed of 1% of 2-AP, 4% of soybean oil, 4% of lecithin, and 91% of water was physically and chemically stable for at least 8 weeks. It gave significantly faster clearance of 2-AP and higher affinity to the organs, especially the liver, compared with the 2-AP in solution, suggesting that it could selectively deliver 2-AP to the liver. Thus, the lipid emulsion with soybean oil and lecithin could be used as a potential dosage form with the liver-targeting property and enhanced stability of sparingly water-soluble 2-AP.     

Formation and Stability Studies of Multiple (w/o/w) Emulsions Prepared with Newly Synthesized Rosin-Based Polymeric Surfactants

The multiple (water-in-oil-in-water, w/o/w) emulsions were prepared using newly synthesized rosin-based polymeric surfactants. The oil phase used was liquid paraffin. These emulsions were evaluated for stability by various methods: conductivity, viscosity, particle size, and visual inspection. The stability studies were carried out at 37°C and 4°C for 1 month. The multiple emulsion prepared with polymer 7 was found to be more stable compared to the emulsions prepared with polymer 2.     

Formation and stability studies of multiple (w/o/w) emulsions prepared with newly synthesized rosin-based polymeric surfactants

The multiple (water-in-oil-in-water, w/o/w) emulsions were prepared using newly synthesized rosin-based polymeric surfactants. The oil phase used was liquid paraffin. These emulsions were evaluated for stability by various methods: conductivity, viscosity, particle size, and visual inspection. The stability studies were carried out at 37°C and 4°C for 1 month. The multiple emulsion prepared with polymer 7 was found to be more stable compared to the emulsions prepared with polymer 2.     

Preparation and characterization of a submicron lipid emulsion of docetaxel: submicron lipid emulsion of docetaxel

Docetaxel, a widely used anticancer agent, has sparingly low aqueous solubility, thus Tween 80 and ethanol need to be added into its formulation, probably resulting in the toxic effects. In this study, we aimed to utilize submicron lipid emulsions as a carrier of docetaxel to avoid these potential toxic vehicles. Preformulation study was performed for rational emulsions formulation design, including drug solubility, distribution between oil and water, and degradation kinetics. Supersaturated submicron lipid emulsion of docetaxel was prepared by temperature elevation method. Soya oil and Miglyol 812 can incorporate docetaxel up to 1.0% (drug to lipid ratio) and were used as the oil phase of emulsions. The optimal formulation of docetaxel is composed of 10% oil phase, 1.2% soybean lecithin, 0.3% Pluoronic F68, and 0.4 or 0.8 mg/mL docetaxel, with particle size in the nanometer range, entrapment efficiency more than 90%, and is physicochemically stable at 4 and 25 degrees C for 6 months. Animal studies showed that docetaxel emulsion has significantly higher area under the curve (AUC) and C(max) in rats compared to its micellar solution. The results suggested that the submicron lipid emulsion is a promising intravenous carrier for docetaxel in place of its present commercially available docetaxel micellar solution with potential toxic effects.     

Stability of orange oil/water nanoemulsions prepared by the PIT method

This article reports the preparation and characterization of orange oil/water nanoemulsions stabilized by commercial nonionic surfactants based on ethoxylated lauryl ether (Ultrol line), by the phase inversion temperature (PIT) method. The orange oil/surfactant/water dispersions were prepared at different HLB values, by varying the concentrations of the surfactants as well as the concentration of the oil phase. The stability of the o/w nanoemulsions and the size distribution of the dispersed particles in these systems in general depended on the concentration of the oil phase used: the emulsions prepared with an oil phase of 14 wt% had smaller droplet size in the dispersed phase than the emulsions prepared in the presence of oil phases of 20 and 30 wt%. The nanoemulsions prepared with pure surfactants were more stable in the presence of Ultrol L60, but the surfactants' cloud point had a strong influence on the stability of the emulsions formed when this was very near room temperature. Because of this, we prepared systems containing mixtures of surfactants. Among these systems, the most stable nanoemulsions were those prepared with a Ultrol L100/Ultrol L20 mixture with HLB of 12.40. This behavior can be attributed to the complete solubilization in mixed micelles of the more hydrophobic surfactant.     

Freeze–thaw stability of emulsions with soy protein isolate through interfacial engineering

In this paper, we examined to the influence of interfacial composition on freeze–thaw stability of oil in water emulsions. An electrostatic layer-by-layer deposition method was used to create the multilayered interfacial membranes with different compositions of primary emulsion (Soy protein Isolate); secondary emulsion (Soy protein Isolate – octenyl-succinate starch); tertiary emulsion (Soy protein Isolate – octenyl-succinate starch – Chitosan). The primary, secondary and tertiary emulsions were subjected to from one to two freeze–thaw cycles (−20 °C for 24 h, +25 °C for 18 h) and then their stability was assessed by ζ-potential, particle size, microstructure and creaming stability measurements. The crystallization behaviour of emulsions was studied by differential scanning calorimetry (DSC). Primary and secondary emulsions were unstable to droplet flocculation when the water phase crystallized, whereas tertiary emulsions were stable, which was attributed to the relatively thick biopolymer layer surrounding the oil droplets. These results showed the interfacial engineering technology used in the study could therefore lead to the creation of food emulsions with improved stability to freezing and thawing.     

Preparation and Characterization of a Submicron Lipid Emulsion of Docetaxel: Submicron Lipid Emulsion of Docetaxel

Docetaxel, a widely used anticancer agent, has sparingly low aqueous solubility, thus Tween 80 and ethanol need to be added into its formulation, probably resulting in the toxic effects. In this study, we aimed to utilize submicron lipid emulsions as a carrier of docetaxel to avoid these potential toxic vehicles. Preformulation study was performed for rational emulsions formulation design, including drug solubility, distribution between oil and water, and degradation kinetics. Supersaturated submicron lipid emulsion of docetaxel was prepared by temperature elevation method. Soya oil and Miglyol 812 can incorporate docetaxel up to 1.0% (drug to lipid ratio) and were used as the oil phase of emulsions. The optimal formulation of docetaxel is composed of 10% oil phase, 1.2% soybean lecithin, 0.3% Pluoronic F68, and 0.4 or 0.8 mg/mL docetaxel, with particle size in the nanometer range, entrapment efficiency more than 90%, and is physicochemically stable at 4 and 25°C for 6 months. Animal studies showed that docetaxel emulsion has significantly higher area under the curve (AUC) and C_max in rats compared to its micellar solution. The results suggested that the submicron lipid emulsion is a promising intravenous carrier for docetaxel in place of its present commercially available docetaxel micellar solution with potential toxic effects.