伊曲康唑固体脂质纳米粒的制备

目的:制备伊曲康唑固体脂质纳米粒,并考察其理化性质.方法:采用乳化-低温固化法制备伊曲康唑固体脂质纳米粒(ITZ-SLN);在脂质、表面活性剂等辅料和主药用量的单因素考察基础上,以包封率为评价指标,采用正交试验设计,优化处方组成和制备工艺;用低温超速离心法测定包封率,透射电镜观察形态,激光粒径分析仪测定粒径和ξ电位.结果:脂质、表面活性剂和主药的用量对ITZ-SLN包封率均有不同程度的影响.以优化处方制备的伊曲康唑固体脂质纳米粒为类球形实体,粒径分布比较均匀,平均粒径为dav=(118.2±15.00)nm,ξ电位(-37.06±0.53)mV,包封率(92.11±1.60)%.结论:乳化-低温固化法制备伊曲康唑固体脂质纳米粒工艺可行.     

正交设计优化伊曲康唑固体脂质纳米粒的处方组成与制备工艺

目的:制备伊曲康唑固体脂质纳米粒(itraconazole solid lipid nanoparticles,ITZ-SLNs)并对其进行物相分析以确定纳米粒的形成。方法:以伊曲康唑(ITZ)为模型药物,硬脂酸为载体材料,采用乳化-低温固化法制备伊曲康唑固体脂质纳米粒(ITZ-SLN),正交试验设计优化处方组成和制备工艺,并对纳米粒的结构形态、粒径、表面电位、包封率、体外释药特性等进行了研究。结果:以优化处方制备的伊曲康唑固体脂质纳米粒为类球形实体,粒径分布比较均匀,平均粒径为dav=(118.2±15.00)nm,Zeta电位为-(37.06±0.53)mV,包封率为(92.11±1.60)%,药物体外释放符合Higuchi方程,经DSC分析证明纳米粒确已形成。结论:伊曲康唑固体脂质纳米粒有望成为新型缓释纳米给药系统。     

槲皮素固体脂质纳米粒的制备

目的: 制备槲皮素固体脂质纳米粒并对其理化性质进行考察。方法: 采用乳化蒸发-低温固化法制备槲皮素固体脂质纳米粒,以正交设计优化处方和制备工艺,超滤法测定包封率,透射电子显微镜对其粒子形态进行观察,并使用激光粒度分析仪测定其粒径和Zeta电位。结果: 经处方优化制备的固体脂质纳米粒平均粒径为(124.2±0.371) nm,Zeta电位为(-22.3±0.315) mV,粒子形态均匀,无粘连,平均包封率为(89.3±1.209)%。结论: 制备槲皮素固体脂质纳米粒的工艺简便可行,包封率较高且纳米粒质量优良。     

单唾液酸四己糖神经节苷脂固体脂质纳米粒的制备方法及性质考查

目的：建立适用于生产的单唾液酸四己糖神经节苷脂（GM1）固体脂质纳米粒的制备方法。方法：分别采用溶剂乳化法和高压乳匀法制备GM1固体脂质纳米粒,并将制备结果进行比较。结果：通过比较两种制备方法制得的GM1固体脂质纳米粒进行外观及稳定性、形态学考查、包封率等指标,同时比较以该固体脂质纳米粒制备的冻干粉针剂性状,发现高压乳匀法获得的固体脂质纳米粒性质较佳。结论：高压乳匀法可作为实际GM1固体脂质纳米粒冻干粉针剂中间体的制备方法。     

环索奈德纳米粒制备及其性质

目的:制备环索奈德固体脂质纳米粒胶体溶液,对其理化性质进行考察。方法:经方法考察,确定采用乳化-溶剂挥发法制备环索奈德纳米粒胶体溶液。在载体材料种类及用量、表面活性剂种类及用量、水相用量等单因素考察基础上,对处方组成进行了响应面优化,确定了最佳处方组成和制备工艺。用高速冷冻离心法和紫外分光光度法测定了包封率、载药量,激光粒径仪测定了粒径、Zeta电位,扫描电镜观察了纳米粒形态,并考察了药物纳米粒胶体溶液的体外稳定性。结果:乳化-溶剂挥发法适合制备环索奈德纳米粒胶体溶液,载体材料组成、药物与载体材料质量比、表面活性剂用量对其粒径影响较大。最佳处方制备的纳米粒呈圆整球状,平均粒径为(96.6±18.4)nm,Zeta电位为(-12.7±2.2)mV,包封率为(94.3±1.4)%,载药量为(10.72±0.23)%,纳米粒溶液在室温条件下不够稳定。结论:研究中处方及制备工艺适合制备环索奈德纳米粒胶体溶液,相关理化性质检测方法可行。     

Box-Behnken效应面法优化姜黄素正负离子固体脂质纳米粒的处方

目的 采用Box-Behnken效应面法筛选姜黄素正负离子固体脂质纳米粒的最优处方.方法 采用乳化蒸发-低温固化法制备姜黄素的固体脂质纳米粒,以固体脂质的质量、卵磷脂的质量和混合表面活性剂为考察对象,以包封率和脂质载药量为考察指标,利用3因素3水平Box-Behnken效应面设计法筛选姜黄素固体脂质纳米粒的最优处方.结果 按最优处方制备固体脂质纳米粒的包封率为94.20％ ±2.55％、脂质载药量为3.49％±0.11％,平均粒径为194.9 ±12.0 nm,Zeta电位为-28.15 ±2.72 mV.结论 采用Box-Behnken效应面法优化姜黄素正负固体脂质纳米粒的处方是有效、可行的.     

2种方法制备银杏内酯长循环固体脂质纳米粒的比较

目的:研究银杏内酯AB长循环固体脂质纳米粒(GAB-LSLN)的制备方法,并探讨GAB-LSLN的主要理化性质。方法:分别采用超声法和高压乳匀法制备GAB-LSLN。在电镜下观察其形态,测定其粒径、Zeta电位和包封率,并在室温下放置4周,观察GAB-LSLN的稳定性。结果:超声法制备的GAB-LSLN在透射电镜下呈片状存在,形态不规则;高压乳匀法制备的GAB-LSLN呈球状,形态规则。超声法和高压乳匀法制备的GAB-LSLN粒径分别为(219.6±14.3)nm和(173.9±10.4)nm(P<0.001);Zeta电位分别为(—21.12±1.03)mv和(—27.43±2.14)mV(P<0.001),包封率分别为(85.05±0.67)%和(92.49±0.88)%(P<0.001)。高压乳匀法制备的GAB-LSLN室温放置4周后,粒径无显著增加(P>0.05)。结论:高压乳匀法制备GAB-LSLN具有粒径小、稳定性和包封率高的特点,优于超声法。     

青藤碱固体脂质纳米粒的制备

目的：以山嵛酸甘油酯为载体材料制备青藤碱固体脂质纳米粒并评价其质量。方法：采用乳化蒸发一低温固化法制备青藤碱固体脂质纳米粒，以正交设计优化其处方和制备工艺。对其粒径、形态、表面电位、包封率等理化性质进行研究，并考察其稳定性。结果：所制固体脂质纳米粒外观形态圆整，平均粒径为208．7nm，Zeta电位为-38．5mV，平均包封率为65．7％。4℃放置2个月，粒径、包封率无明显变化。结论：青藤碱固体脂质纳米粒的制备，为开发其新制剂奠定了实验基础。     

马钱子碱固体脂质纳米粒制备及质量评价

目的：以乳化蒸发-低温固化法制备马钱子碱固体脂质纳米粒并评价其质量。方法：在单因素考察的基础上以正交试验设计优化、筛选最佳处方。用透射电镜观察固体脂质纳米粒的形态,HPLC法测定马钱子碱固体脂质纳米粒的包封率,激光散射测定Zeta电位和粒度分布,并考察其稳定性。结果：所制固体脂质纳米粒外观形态圆整,平均粒径为116nm,Zeta电位为-29．98mv,包封率为50．7％,载药量为2．25％。4℃放置1个月,粒径、包封率无明显变化。结论：本研究制备的马钱子碱固体脂质纳米粒粒径分布窄,稳定性好,为开发马钱子碱低毒长效的制剂奠定了实验基础。     

薄膜-超声法制备芦丁固体脂质纳米粒的研究

目的优化薄膜-超声法制备芦丁固体脂质纳米粒的处方。方法以包封率为指标,采用正交设计优化法考察硬脂酸和大豆卵磷脂的用量、吐温-80和聚乙二醇-400的体积分数对包封率的影响,优选最佳处方。用透射电镜观察外观形态,用电位/纳米粒度分析仪分析纳米粒的粒径及Zeta电位,用透析法评价体外释药特征。结果以最佳处方制备的芦丁固体脂质纳米粒呈类球形,平均粒径为195.8±11nm,Zeta电位为-20.65±0.6mV,平均包封率为86.31%,72h体外累积释放87.32%。结论按最佳处方工艺制备的芦丁固体脂质纳米粒具有较高的包封率和较好的缓释效果。     

人参皂苷Rd固体脂质纳米粒的体外释放和大鼠的在体吸收

目的研究人参皂苷Rd固体脂质纳米粒(Rd-SLN)的体外释药特性、在大鼠肠道的吸收和体内药物动力学行为。方法采用透析法测定Rd-SLN体外释药速率;通过大鼠在体分段肠回流实验,研究Rd-SLN的肠道吸收行为;建立血浆样品中人参皂苷Rd的HPLC分析方法,在大鼠灌胃给药后测定不同时间的血药浓度,观察Rd-SLN在体内的吸收和药动学特征。结果Rd-SLN具有缓释特征。在十二指肠和空肠段,Rd-SLN与人参皂苷Rd对照溶液的吸收率差异没有显著性;在回肠和结肠段,Rd-SLN与对照溶液的吸收率差异有显著性。Rd-SLN在回肠段的吸收率高于其它肠段。与对照组相比,Rd-SLN组的血药浓度水平维持时间更长,其Cmax、MRT、AUMC和AUC均明显增加。结论Rd-SLN具有一定的缓释作用,其在回肠的吸收优于其他肠段,并且能明显提高人参皂苷Rd的生物利用度。     

Preparation and evaluation of thiomer nanoparticles via high pressure homogenization

The aim of this study was to establish and evaluate a high pressure homogenization method for the preparation of thiomer nanoparticles. Particles were formulated by incorporation of the model protein horseradish peroxidase in chitosan-glutathione (Ch-GSH) and poly(acrylic acid)-glutathione (PAA-GSH) via co-precipitation followed by air jet milling. The resulting microparticles were suspended in distilled water using an Ultraturax and subsequently micronized by high pressure homogenization. Finally, resulting particles were evaluated regarding size distribution, shape, zeta potential, drug load, protein activity and release behaviour. The mean particle size after 30 cycles with a pressure of 1500 bar was 538 ± 94 nm for particles consisting of Ch-GSH and 638 ± 94 nm for particles consisting of PAA-GSH. Nanoparticles of Ch-GSH had a positive zeta-potential of +1.03 mv, whereas nanoparticles from PAA-GSH had a negative zeta potential of ?6.21 mv. The maximum protein load for nanoparticles based on Ch-GSH and based on PAA-GSH was 45 ± 2% and 37 ± %, respectively. The release profile of nanoparticles followed a first order release kinetic. Thiolated nanoparticles prepared by a high pressure homogenization technique were shown to be stable and provide controlled drug release characteristics. The preparation method described here might be a useful tool for a more upscaled production of nanoparticulate drug delivery systems.     

阿苯达唑纳米晶体的制备与表征

目的： 采用微射流高压均质-喷雾干燥法技术制备阿苯达唑纳米晶体,并进行表征和体外溶出考察。方法： 釆用高压均质法制备阿苯达唑纳米混悬液,并进一步喷雾干燥得纳米晶体。通过正交试验优化制备工艺;对最佳制备工艺所得纳米晶体进行粒径测定、DSC分析和傅里叶红外图谱分析,并测定其体外溶出度。结果： 微射流高压均质最佳制备工艺条件：在均质温度35℃,103.44 MPa和137.93 MPa下各循环20次,得到纳米混悬液平均粒径为（363.52±1.5） nm。喷雾干燥最佳工艺为：进样速度5 mL·min^-1,进风温度180℃,在此条件下得粉率（66.71±0.96）%,含水量（6.61±0.16）%,平均粒径367.34±0.68 nm。DSC分析及傅里叶红外图谱结果表明制备成纳米晶体后形成新的物象;体外溶出度实验结果表明,纳米晶体的溶出度显著高于原料药和混合物。结论： 微射流高压均质-喷雾干燥工艺,可以制备平均粒径小且较为均匀的纳米晶体;纳米化后形成新的物象,可以明显提高阿苯达唑的溶出性能,利于改善药物的口服吸收,这为阿苯达唑进一步开发提供了依据。     

Study of solid lipid nanoparticles with respect to particle size distribution and drug loading

This work deals with the formulation and development of Solid Lipid Nanoparticles (SLN) using pressure homogenization technique, nimesulide being used as the model drug. Main emphasis of the work was to study the effect of individual process parameters (homogenization pressure and homogenization cycles) and formulation parameters (lipid concentration and surfactant concentration) on particle size distribution and drug loading. Particle size distribution data indicate that by optimizing the homogenization process and formulation parameters it is possible to produce SLN within a desired size range as required for carrier mediated drug targeting. Approaches to improve drug loading efficiency indicate that drug loading was higher in case of SLN prepared from glyceryl beheanate, palmitostearate and glyceryl tristearate + span 60 as compared to monoacid triglyceride (MAT) tristearate. Thermal analysis by differential scanning calorimetry of the drug loaded SLN indicates the solid nature of the lipid carrier as required for sustained drug release.     

莪术油固体脂质纳米粒的制备

目的研究影响莪术油固体脂质纳米粒制备的主要因素。方法采用高压均质法制备莪术油固体脂质纳米粒混悬液,以单因素考察和正交设计法筛选出比较理想的处方和工艺,并考察其形态、粒径、载药量及包封率。结果所制得的固体脂质纳米粒为圆整的类球形实体粒子,表面光滑,平均粒径为80.3nm,载药量为11.82%,包封率为81.75%。结论高压均质法可用于莪术油类液体药物固体脂质纳米粒的制备。     

非诺贝特胶囊剂及家犬体内生物利用度

目的采用纳米分散技术制备非诺贝特胶囊剂,以提高其溶出度及生物利用度。方法用反溶剂沉淀法和高压匀质法制备非诺贝特纳米混悬剂,并通过喷雾干燥将其固化以制备胶囊剂,用差示扫描量热法(differential scanning calorimetry,DSC)和X-射线粉末衍射分析表征药物在胶囊剂中的存在状态,并测定药物的溶出度及家犬体内的生物利用度。结果非诺贝特以纳米晶体状态分散于胶囊剂中,自制胶囊溶出度为国产胶囊的3倍,相对生物利用度为国产胶囊的(274.5±15.6)%。结论自制非诺贝特胶囊剂可以通过增加非诺贝特的分散度来提高药物的溶出度与生物利用度。     

Nanosuspensions as advanced printing ink for accurate dosing of poorly soluble drugs in personalized medicines

Folic acid was used as a model drug to demonstrate the advantages of formulating poorly soluble drugs as nanosuspensions and their use in an inkjet-type printing technique to produce personalized medicines. 10% folic acid nanosuspensions stabilized with Tween 20, a stabilizer showing the best wetting potential for folic acid, were prepared via high pressure homogenization. The particle size of the folic acid nanosuspension was well below 5 μm being a prerequisite for inkjet type printing technique. A good reproducibility of the particle size of folic acid nanosuspension prepared via high pressure homogenization was found. As indicated by the zeta potential the formulation showed a good storage stability. High pressure homogenization had no influence on the crystalline state of folic acid. An increase in the saturation solubility by 53.7% was found reducing the particle size from the micrometer range to the nanometer range. The dissolution velocity of the folic acid nanosuspension was significantly enhanced compared to a folic acid suspension, i.e. after 5 min 78.6% of the folic acid was dissolved from the nanosuspension and only 6.2% from the suspension. Moreover, the printing of 10% folic acid nanosuspension could be successfully demonstrated.     

Influences of process parameters on nanoparticle preparation performed by a double emulsion pressure homogenization technique

The preparation of nanoparticles (NP) as an improved colloidal carrier system for proteins was investigated. Bovine serum albumin (BSA) was used as model drug. Owing to the high solubility of the protein in water, the double emulsion technique has been chosen as one of the most appropriate method. In order to both reaching submicron size as well as increasing the grade of monodispersity compared to previous preparation techniques, a microfluidizer as homogenization device was used. All experiments were performed using two biodegradable polymers, poly[D,L-lactic-co-glycolic acid] 50/50 (PLGA) and poly[epsilon-caprolactone] (PCL). The homogenization procedure has been optimized with regard to particle size and monodispersity by studying the influence of the homogenization time as well as the amount of polymer and surfactant in the external aqueous phase. The drug loading has been improved by varying the concentration of the protein in the inner aqueous phase. By increasing the protein concentration in the inner aqueous phase the polydispersity was slightly higher, while the particle size was not influenced significantly. The BSA encapsulation efficiency decreased with higher protein concentration in the inner aqueous phase. All release profiles were characterized by a initial burst effect, a higher release rate was obtained after 4 weeks for PLGA NP (60%) compared with PCL NP (47%).     

TE-01静脉注射乳剂的制备及处方工艺优化

目的 制备TE-01静脉注射乳剂并进行处方工艺优化.方法 采用高压均质方法制备TE-01乳剂,并通过正交设计优选TE-01静脉注射乳剂的最佳处方及其制备工艺.结果 TE-01静脉注射乳剂最佳处方及工艺为蛋黄卵磷脂含量1.2％,分散转速16 000 r·min-1,均质压力550 bar.结论 高压均质法可以制备出性质稳定的TE-01乳剂.     

熊果酸脂肪乳注射液的制备及体外评价

目的：制备熊果酸脂肪乳注射液,并对其理化性质进行评价。方法：采用高压均质法制备熊果酸脂肪乳注射液,考察脂肪乳的粒径分布、Zeta电位和微观形态,并初步研究熊果酸脂肪乳的稳定性。结果：熊果酸脂肪乳注射液的平均粒径为（203.6±37.1）nm,Zeta电位为（-36.5±3.6）mV;透射电镜显示脂肪乳注射液粒径均一,呈球状分布。稳定性研究结果表明,熊果酸脂肪乳在25℃/60%条件下放置6个月内稳定。结论：高压均质法制备熊果酸脂肪乳注射液工艺简单易行,有望应用于工业化生产。