喷雾干燥法制备南极磷虾油微囊处方和工艺研究

摘要：目的 采用喷雾干燥法制备南极磷虾油微囊并进行工艺优化。方法 以乳剂的乳化稳定性及微囊包埋率为评价指标,采用正交试验和Box-Behnken设计考察各因素对南极磷虾油乳剂的稳定性及微囊包埋率的影响,利用扫描电镜观察微囊的表面形态。结果 乳剂制备最佳工艺为乳化剂用量1%、阿拉伯胶用量10%、变性淀粉用量15%、大豆分离蛋白用量15%、麦芽糊精用量60%;微囊最佳制备工艺为均质压力34 Mpa、进风温度为165 ℃、进料速度为12.5 mL/min。结论 经优化后乳剂的乳化稳定性为0.91,微囊包埋率达82.46%。     

替硝唑原位固化缓释凝胶的处方研究

目的:应用Box-Behnken法设计并优化替硝唑原位固化缓释凝胶处方.方法:通过体外释放度的单因素影响试验确定考察因素与水平,以凝胶粘度、遇水固化时间、释放时间为响应变量,应用Box-Behnken法进行处方筛选与优化.结果:优化处方为35.3%(w/w)单甲氧基聚乙二醇-聚乳酸(mPEG-PDLLA 10/90),5.9% (w/w)替硝唑和58.8% (w/w)N-甲基-2-吡咯烷酮(NMP).该凝胶体外释放时间达192 h,无突释现象.结论:通过Box-Behnken法成功实现了替硝唑原位固化缓释凝胶的处方筛选.     

正交法研究双嘧达莫微囊的制备工艺

目的 :研究双嘧达莫微囊的制备工艺。方法 :用正交设计法对双嘧达莫微囊的制备工艺进行研究。结果 :用单凝聚法制备双嘧达莫微囊 ,其包裹率与囊心囊材比有显著性差异 (P<0.05) ,而搅拌速度能影响微囊的粒径 ,当囊心囊材比为1∶4、成囊温度50℃、搅拌速度为400r/min时 ,包裹率最高 ,囊径最小。结论 :该法工艺简单、可靠     

单凝聚法制备姜黄素微囊的工艺研究

摘 要 目的：优化姜黄素微囊的制备工艺。 方法: 采用单凝聚法制备姜黄素微囊,以包封率、载药量和产率为指标,采用正交试验对明胶浓度、芯壁比、成囊温度、搅拌速度等因素进行考察,并对其形态与粒径进行表征。 结果: 单凝聚法制备姜黄素微囊的最优处方为：明胶浓度5%,芯壁比1∶2,成囊温度50℃,搅拌速度500 r·min-1。制备的姜黄素微囊外观圆整,大小均匀且无粘连。 结论: 单凝聚法制备姜黄素微囊工艺简单,包封率高,载药量大。     

黄芩素分子印迹整体柱的制备研究

目的:制备黄芩素分子印迹整体柱并研究其特异识别能力。方法:以黄芩素分子为模板,甲基丙烯酸(MAA)为功能单体,乙二醇二甲基丙烯酸酯(EDMA)为交联剂,DMF和十二醇为混合致孔剂,偶氮二异丁腈(AIBN)为引发剂,采用原位聚合法合成黄芩素分子印迹整体柱,并考察了印迹整体柱在不同有机相中对黄芩素与汉黄芩素的识别能力,以及流速、柱温对保留因子与分离因子的影响。结果:模板分子与功能单体之间的比例以1∶6为最佳,得到的分子印迹整体柱对模板分子具有特异的识别能力,黄芩素和其结构类似物汉黄芩素达到较好的分离。结论:合成的印迹整体柱对模板分子具有很强的亲和力和良好的识别能力,可以用做黄芩素的分离材料。     

穿琥宁直肠用原位凝胶的处方研究

目的:研究穿琥宁直肠用原位凝胶的处方和制备工艺。方法:以外观、黏度突变温度、胶凝温度、稳定性等为指标,采用单因素试验考察泊洛沙姆的种类和用量、抗氧化剂和抗菌剂种类;以穿琥宁含量降低百分率为指标,以乙二胺四乙酸二钠质量分数、苯甲醇质量分数、羟丙基-β-环糊精(HP-β-CD)质量分数为考察因素,采用正交试验结合单因素试验优选抗菌剂的用量和抗氧化剂的种类和用量;并对有效期进行预测。结果:优选的处方为10 g穿琥宁,18 g泊洛沙姆407,6.0 g泊洛沙姆188,0.5 g苯甲醇、6 g HP-β-CD,加水至100 g;胶凝温度为(36.5±0.5)℃;制剂有效期为1.57年。结论:优选的处方合理、可行,可用于制备穿琥宁直肠用原位凝胶。     

左旋多巴微囊制备工艺的研究

目的以乙基纤维素为囊材,优选左旋多巴微囊的制备工艺。方法以微囊的包封率及载药量为评价指标,采用正交实验优选左旋多巴微囊液中干燥法制备工艺条件,并对制备的微囊进行质量检查。结果优选出的制备工艺为:囊材与药量比例为0.6∶1.4,油水相比例为105∶30,PVP量为0.2g,验证实验表明,优化工艺所制左旋多巴微囊的平均载药量为54.94%,平均包封率为89.2%。质量检查结果表明,微囊外观圆整且无粘连现象,大部分微囊的粒径分布在300～600μm范围内。优选出的左旋多巴微囊在体外具有明显的缓释效果。结论采用液中干燥法制备左旋多巴微囊,工艺稳定可靠,操作简便,工艺条件合理、可行。     

盐酸米诺环素缓释原位凝胶的处方工艺研究

<正>缓释凝胶为溶剂敏感型原位凝胶,可将其注入到牙周袋内,通过基质的水合作用,使制剂固定黏附于牙周袋内,又通过基质的缓释性能,保证了其可在较长时间内释放活性成分,维持局部有效药物浓度。本文研究盐酸米诺环素缓释原位凝胶的材料筛选和工艺选择,并进行了处方优化。1仪器与试药1.1实验仪器:85-2A型恒温磁力加热搅拌器,SartoriusBS110S电子分析天平,光学显微镜。     

复凝聚法制备槲皮素微囊的工艺

目的:优选以明胶和阿拉伯胶为囊材制备槲皮素微囊的最佳工艺条件。方法:采用复凝聚法,以槲皮素为囊芯物,用明胶和阿拉伯胶作囊材,取pH、囊材浓度及搅拌速度3个为考察因素,用正交试验探讨制备槲皮素微囊的最佳条件。结果:当pH为4.0,囊材为3%,搅拌速度为150 r.min-1时为最佳工艺条件。结论:本法工艺简便、稳定,具有应用前景。     

用正交法对阿司匹林微囊制备工艺的研究

本文用正交设计法对阿司匹林微囊的制备工艺进行了研究，结果表明用单凝聚法制备阿司匹林微囊；其包裹率与囊心囊材比和成囊温度有显著性关系，而搅拌速度则能影响微囊的粒径，当囊心囊材比为1：4，成囊温度50℃，搅拌速度为600r／min时，包裹率最高，囊径最小。同时以一阶导数光谱法测定微囊中阿司匹林含量，方法简单方便，结果准确。     

Preparation of microcapsules and control of their morphology

For the preparation of microcapsules using the W/O/W (water in oil in water) emulsion system, it is essential to control various factors such as the dispersed state of the organic phase in the W/O/W emulsion, the difference in the solute concentration between the inner and outer aqueous phases and the volume fraction of the dispersed phase. In this study, cross-linked microcapsules were prepared by the in-situ polymerization of styrene and divinylbenzene and biodegradable microcapsules were prepared by the solvent evaporation method. The effects of the preparation conditions on the capsule morphology and entrapment efficiency of water-soluble materials were investigated. The average diameter of the surface pores and internal hollows were controlled on a sub-micron order by changing the preparation conditions such as diluent concentration, volume fraction of the dispersed droplets in the W/O (water in oil) emulsion, surfactant concentration monomer ratio and salt concentration in the outer aqueous phase. Furthermore, the water-soluble materials were completely entrapped in the biodegradable microcapsule by changing the preparation conditions such as volume fraction of the dispersed droplets in the W/O emulsion, salt concentration in the inner and outer aqueous phases, polymer concentration and supersonic irradiation of the W/O droplets.     

Preparation of double-encapsulated microcapsules for mitigating drug loss and extending release

The double-encapsulated microcapsules were prepared by the non-solvent addition, phase-separation method to form core material and, encapsulated with the O/W emulsion non-solvent addition method to increase drug loading and regulate drug release rate. The drug used was theophylline, which is watersoluble. Dichloromethane and n-hexane were used as the solvent and non-solvent, respectively. This study investigated how various core material and microcapsule EC/TH ratios affect the drug loss, particle size, surface morphology and release rate. The drug loss of the double-encapsulated microcapsules was 12.8% less than that of microcapsules prepared by the O/W emulsion non-solvent addition method alone. The particle size of these double-encapsulated microcapsules decreased as the concentration of EC polymer was increased in the second encapsulation process. The roughness of their surface was also in proportion to the concentration of polymer solution used in the second encapsulation process. The dissolution study showed that the T 20 of the double-encapsulated microcapsules ranged from 2-35.4 h, while that of the O/W emulsion non-solvent addition method microcapsules was from 2.7-7.7 h. The greater the level of EC in the polymer solution, the slower the release rate of the drug from the microcapsules when the EC was not over the critical amount.     

Influence of synthesis parameters on properties and characteristics of poly (urea-formaldehyde) microcapsules for self-healing applications

Abstract

Poly(urea-formaldehyde) (PUF) microcapsules filled with dicyclopentadiene (DCPD) were prepared by in situ polymerisation and the effect of synthesis parameters, such as pH of the solution and agitation rate, on microcapsules size and shell thickness was evaluated. Scanning electron microscopy (SEM) and Fourier transform infra-red spectroscopy (FTIR) were performed. Adjusted pH conditions (pH = 3.5) and agitation rate (1350?RPM) were found using a design of experiments (DOE). SEM results indicated that microcapsule size was directly affected by agitation rate, whereas shell thickness was mostly affected by pH. After obtaining adjusted synthesis conditions, microcapsules presenting mean size of 60?µm and mean shell thickness of 4?µm were embedded in an epoxy matrix for evaluating the self-healing effect. FTIR and SEM analyses in damaged samples suggested that a healing agent was delivered to the crack location.     

Preparation and stability of agarose microcapsules containing BCG

An emulsification/internal gelation method of preparing small-sized agarose microcapsules containing Bacillus Calmette-Guérin (BCG) is reported. Agarose microcapsules have been prepared by the emulsification of the hydrogel within a vegetable oil followed by its gelation due to the cooling of the system. Four different oils (sesame, sweet almonds, camomile and jojoba) were assayed. The rheological analysis of the oils showed a Newtonian behaviour, with viscosity values of 37.7, 51.2, 59.3 and 67.1 mPa s for jojoba, camomile, sesame and sweet almonds oil, respectively. The particle size of the microcapsules obtained ranged from 23.1 #181;m for the microcapsules prepared with sweet almonds oil to 42.6 #181;m for those prepared with jojoba. The microcapsule particle size was found to be dependent on the viscosity of the oil used in the emulsification step. The encapsulated BCG was identified by the Difco TB stain set K, followed by observation under optical microscopy. Once prepared, microcapsules were freeze-dried using 5% trehalose as cryoprotectant and the stability of the microcapsules was assayed during 12 months storage at room temperature, observing that agarose microcapsules were stable after 12 months storage, since there was no evidence of alteration in the freeze-dried appearance, resuspension rate, observation under microscope, or particle size.     

RP-HPLC测定番茄红素微胶囊的含量

目的建立反相高效液相色谱法测定番茄红素微胶囊中番茄红素含量的方法。方法采用反相高效液相色谱法,色谱柱为美国Alltech Alltima C1（84.6mm×250mm,5μm）,流动相为甲醇-四氢呋喃-水（66∶30∶4,V/V/V）,流速为1.5mL·min^-1,检测波长为472nm。结果线性范围为 3.6～18μg·mL^-1,相关系数r=0.9998,平均回收率为99.81%～101.06%,RSD为1.12%～1.83%,日内和日间精密度的RSD分别在1.73%～2.54%、2.85%～3.34%之间。结论本文采用反相高效液相色谱法初步建立了番茄红素微胶囊中番茄红素的定量方法, 该方法准确, 快速, 重现性好。     

Preparation of alginate/chitosan microcapsules and enteric coated granules of mistletoe lectin

The aqueous extract of European mistletoe (Viscum album, L.) has been used in cancer therapy. The purified mistletoe lectins, main components of mistletoe, have demonstrated cytotoxic and immune-system-stimulating activities. Korean mistletoe (Viscum album L. coloratum), a subspecies of European mistletoe, has also been reported to possess anticancer and immunological activities. A galactose- and N-acetyl-D-galactosamine-specific lectin (Viscum album L. coloratum agglutinin, VCA) with Mr 60 kDa was isolated from Korean mistletoe. Mistletoe preparations have been given subcutaneously due to the low stability of lectin in the gastrointestinal (GI) tract. In the present study, we investigated the possibility of alginate/chitosan microcapsules as a tool for oral delivery of mistletoe lectin. In addition, our strategy has been to develop a system composed of stabilizing cores (granules), which contain mistletoe lectin, extract or powder, coated by a biodegradable polymer wall. Our results indicated that successful incorporation of VCA into alginate/chitosan microcapsules has been achieved and that the alginate/chitosan microcapsule protected the VCA from degradation at acidic pH values. And coating the VCA with polyacrylic polymers, Eudragit, produced outstanding results with ideal release profiles and only minimal losses of cytotoxicity after manufacturing step. The granules prepared with extract or whole plant produced the best results due to the stability in the extract or whole plant during manufacturing process.     

Mechanical strength of single microcapsules determined by a novel micromanipulation technique

A micromanipulation technique has been developed to measure the bursting force of single dry microcapsules coated onto a surface, such as those normally used in carbonless copying paper. For measuring the bursting force of a given microcapsule, a single fine probe with a flat end about 10mum in diameter was used to squeeze the microcapsule against a flat surface until it burst. The force being imposed on the microcapsule was measured by a transducer connected to the probe. The bursting force and diameter of single dry microcapsules in two samples, different in size and wall thickness, were measured by this technique. The bursting force of the microcapsules in one sample ranged from 50 to 220muN and the diameter from 1.3 to 7.0mum, whilst the bursting force in the other was from 20 to 175muN and the diameter from 0.7 to 3.7mum. This technique makes it possible to compare the mechanical strength of microcapsules made of different formulations, and to infer information about microcapsule mechanical properties.     

Preparation of microcapsules with narrow-size distribution by complex coacervation: Effect of sodium dodecyl sulphate concentration and agitation rate

In this paper, microcapsules with narrow-size distribution, in which the core materials are a kind of suspension containing pigment scarlet powders dispersed in dyed tetrachloroethylene with Span-80 as an emulsifier, are prepared by complex coacervation through controlling sodium dodecyl sulphate (SDS) concentration and agitation rate. The microcapsules, formed in optimized process of 0.01 wt% SDS and 800 rpm, are ～40 μm in diameter. The phase diagram for the gelatin/SDS/water system indicates that the concentration of SDS in the experiments is outside of the complex formation zone to form a gelatin–SDS complex. Consequently, SDS preferential adsorbs and enriches on the surface of the core droplets due to its higher surface activity. Then, gelatin deposits with SDS at the core droplet/water interface to form a primary layer of complexation. Subsequently, with the pH lower than the isoelectric point of gelatin, complex coacervate of gelatin and gum arabic grows on the primary layer surface and finally deposits on the droplets to form a secondary layer. On the whole, the research indicates that the existence of SDS not only decreases the droplet diameters and centralizes the droplets size distribution, but also accelerates coacervation of gelatin and gum arabic to reach the core droplet/water interface, forming no aggregating microcapsules.     

Polyacrylate resin microcapsules for taste masking of antibiotics

Abstract

Various microencapsulated dosage forms were prepared to limit the release of an antibiotic in solution for up to 3 days and in the oral cavity following per oral administration. An experimental antibiotic, clarithromycin (TE-031), was used in these studies. The drug was first encapsulated in gelatin followed in some cases by crosslinking with glutaraldehyde. The gelatin microcapsules were then coated with acrylic resins (Eudragit®), whose solubility properties vary according to pH. A non-solvent coacervation technique was used to apply the Eudragit resins. It was found that crosslinking the gelatin retarded release of TE-031 somewhat relative to that from uncrosslinked gelatin microcapsules in a 72 h release experiment conducted at room temperature. Coating the gelatin microcapsules with Eudragit resins L100, S100, or E100 slowed the release of TE-031 further still; less TE-031 was released over 72 h from the Eudragit-coated formulations prepared with crosslinked gelatin compared with formulations prepared with uncrosslinked gelatin. The Eudragit ElOO-coated crosslinked gelatin microcapsule formulation was most effective in preventing release of the TE-031 under simulated conditions of storage in an aqueous solution.     

甲硝唑阴道用原位凝胶的处方设计及体外质量评价

目的:研制甲硝唑阴道用原位凝胶,并考察其体外质量.方法:以卡波姆及泊洛沙姆为混合凝胶基质,筛选其最佳配比,制备甲硝唑阴道用原位凝胶.对其体外流变性、黏附性进行考察,并与上市甲硝唑阴道用凝胶做对照,考察其阴道滞留性.结果:原位凝胶的最佳基质配比为泊洛沙姆407的质量分数为17.5%,卡波姆971P的质量分数为1.5%.黏附力测定结果表明其具有较大的温度敏感性.与上市产品相比,原位凝胶可显著增加阴道滞留性.结论:该原位凝胶具有显著的温度敏感性,本品值得进一步研发.