海洋多糖BTH缓释微球的制备及释放特性研究

目的 以海藻酸钠与壳聚糖为载体材料制备苯并[l,2,3]噻二唑-7-硫代羧酸甲酯(BTH)缓释微球并研究其释放特性。 方法 采用乳化-外源凝胶法制备BTH缓释微球,通过傅里叶变换红外光谱(FT-IR)验证BTH包封于微球当中,利用高效液相(HPLC)外标法测定微球的包封率、载药量以及不同pH溶液中的释放曲线。结果 BTH被均匀的分散在缓释微球当中,平均载药量为11.14%,平均包封率为81.52%,微球可持续释放12天,累计释放量达到61%。 结论 制备的BTH缓释微球形态圆整,表面光滑,成球性好,载药量与包封率较高,具有显著的缓释效果。     

载环孢素A海藻酸钙-壳聚糖微球的制备及体外释放特性

目的:针对角膜移植术后免疫抑制治疗需求,制备眼部局部给药的小粒径载环孢素A缓释微球,并进行体外释放考察。方法:以海藻酸钠、壳聚糖为载体材料,采用静电液滴工艺,通过向制备体系添加表面活性剂,制备小粒径载环孢素A微球,设计正交试验优化处方工艺,扫描电镜观察微球表面形态,动态透析法考察微球的体外释放特性。结果:所制微球形态良好,粒径分布窄,平均粒径为(12.4±0.8)μm,包封率为(82.8±1.8)%,载药量为(50.1±1.2)%,体外释放行为用Higuchi方程拟合效果最好。结论:采用静电液滴工艺,通过减小制备体系的表面张力,制备了球形度优良、粒径小、包封率和载药量较高的载环孢素A的壳聚糖-海藻酸盐缓释微球,所得制剂的体外释药规律服从扩散机制。     

芹菜素壳聚糖微球的制备及体外释药研究

目的以芹菜素为模型药物、脱乙酰壳聚糖为药物载体,制备芹菜素壳聚糖微球,并测定微球中芹菜素的体外释放度。方法采用复乳-乳化化学交联法制备微球,正交试验优化微球制备的工艺,高效液相色谱法检测芹菜素含量。结果最佳工艺制备4批微球,形态良好,微球圆整,平均载药量为8.54%,平均包封率为69.69%,平均粒径为84.33μm。微球在pH 6.8和pH 7.4的磷酸盐缓冲液中释放36 h。结论所选制备工艺稳定,适用于芹菜素壳聚糖微球的制备,体外药物释放结果显示,微球具有良好的缓释效果。     

奥沙普秦壳聚糖-海藻酸钠缓释微球的制备

目的：目的：选择奥沙普秦作为模型药制备壳聚糖-海藻酸钠缓释微球。方法：采用滴制法制备奥沙普秦壳聚糖-海藻酸钠缓释微球，通过正交试验设计优化了处方和工艺，考察其理化特征及体外释药行为。结果：优化处方制得的微球包封率及载药量分别为98．36％和16．26％，平均粒径为（346．6±164．1）μm；1h药物释放达到36％，随后药物的释药行为是一个缓释过程。结论：制得了载药量较大，包封率较高的奥沙普秦壳聚糖-海藻酸钠缓释微球。     

去甲斑蝥素壳聚糖微球的制备及其体外释放特性

目的:制备去甲斑蝥素壳聚糖微球,并考察其体外释放特性.方法:以液体石蜡为油相,Span-80为乳化剂,甲醛作为交联剂,采用乳化-交联法制备去甲斑蝥素壳聚糖微球.均匀设计优化制备工艺,扫描电镜观察微球表面形态,动态透析法检测微球的体外释放特性.结果:制备的微球形态圆整,粒径分布较为均匀,平均粒径(25±10)μm,载药量(15.08±2.85)%,包封率(57.80±1.35)%.微球在0.1 mol·L-1HCl、磷酸盐缓冲液(pH值5.3)和生理氯化钠溶液中的释放均遵循Higuchi方程.结论:所优化的制备工艺简单易行,载药量高,缓释作用显著.     

口服利福平海藻酸钠微球的制备

［摘要］目的研制口服利福平海藻酸钠微球。方法采用静电液滴法制备利福平海藻酸钠微球，测定粒径大小、包封率、载药量及其影响因素，考察微球的体外释放特点。结果微球球形圆整，分散性好，平均粒径70.2 μm，包封率83.5%，载药量17.1%，在模拟肠液中的释放呈快慢相，时间长而药物释放完全。结论以海藻酸钠、硬脂酸为材料，用静电液滴法制备利福平微球，球径小、包封率高、释药时间长，工艺简便。     

盐酸维拉帕米缓释微球的制备及其质量评价

目的:制备维拉帕米缓释微球,并对其进行质量评价.方法:采用低温喷雾干燥法制备盐酸维拉帕米缓释微球,评价内容包括:微球的粒径及其分布、微球含药量、载药量和包封率、收率以及不同pH值下的释放速率.结果:成功制备了盐酸维拉帕米缓释微球,平均收率为28.97%,所得微球55%以上的粒径在3.0~5.0μm,载药量为26.11%,包封率为76.40%.结论:微球的体外累积释放度完全符合Higuchi方程,初步证实该微球的释放属于骨架溶蚀性过程.     

阿奇霉素壳聚糖-海藻酸钠肠溶微球的制备和评价

目的:制备阿奇霉素壳聚糖-海藻酸钠肠溶微球,并评价各因素对微球性质的影响.方法:以壳聚糖-海藻酸钠为基质材料,采用复凝聚法制备阿奇霉素壳聚糖-海藻酸钠肠溶微球.通过单因素考察研究对粒径、收率和包封率影响较大的因素,以包封率和释放度为指标进行正交设计优化最佳处方.结果:海藻酸钠浓度为3％、氯化钙浓度为2.5％、壳聚糖浓度为0.25％和投药量为20％为最佳处方.该处方制得的微球形态圆整,粒径分布合理,包封率和收率均较高.体外溶出试验表明,该条件制得的微球在酸中的释放量小于10％,可减少阿奇霉素的胃肠道不良反应;在pH6.8的缓冲液中快速释放,能迅速达到最小抑菌浓度(MIC).结论:阿奇霉素壳聚糖-海藻酸钠肠溶微球能有效避免药物在酸性环境中释放.     

苦参碱壳聚糖微球的制备及体外释药

目的:以壳聚糖为囊材制备苦参碱结肠靶向给药微球及评价其体外释药情况。方法:用乳化化学交联法制备微球,以微球的粒径分布百分数、载药量及包封率为优化指标对影响微球制备的主要因素用正交试验设计优化制备条件;并对最佳制备工艺制得的微球进行3种不同递质(人工胃液、人工肠液及大鼠结肠液)中的体外释放度评价。结果:制得的苦参碱壳聚糖微球在电镜下,球形表面圆整,粒径分布适宜,微球平均粒径为(68.3±2.7)μm,平均载药量为(16.0±0.5)%,平均包封率为(66.3±4.2)%。苦参碱壳聚糖微球在人工胃液中2h不释药;在人工肠液中4h内释放不到1%,96h释药不到10%;在含大鼠结肠内容物的磷酸盐缓冲液(pH6.8)中4h释放10%左右,36h释药近50%,此后释药趋于缓慢,96h释药近80%。结论:苦参碱壳聚糖微球几乎不在上消化道释药,而是在结肠靶向释药。     

大蒜素/有机凹凸棒黏土/海藻酸钠/壳聚糖复合微球的制备及其性能

目的制备大蒜素/有机凹凸棒黏土/海藻酸钠/壳聚糖复合微球(ASCM),并研究其载药性能。方法采用复凝聚法制备了ASCM,以复合微球的载药量和包封率为指标,以大蒜素(DATS)为模型药物,考察了有机凹土(OA)/海藻酸钠(SA)质量比、药物含量、复合温度对微球载药性能的影响,并比较了OA加入前后微球的溶胀性能和缓释性能。结果加入OA后,当复合微球中OA:SA为1:3,OA:DATS为1:1时,其载药量和包封率由原来的12.3%和42.3%分别提高到16.8%和66.5%,而在pH 6.8的磷酸盐缓冲溶液中累积释放率降低。结论复合微球可以作为药物的缓释载体。     

Notel长效微球制剂的制备和评价

目的：制备并评价Notel聚乳酸-羟基乙酸共聚物（PLGA）长效缓释微球。方法：采用乳化-溶剂挥发法制备Notel缓释微球,以载药量、包封率、体外释放为评价指标,考察高分子材料、高分子溶液浓度、硬脂酸、不同pH的聚乙烯醇（PVA）溶液等因素对微球的影响,筛选最优处方并制备微球,考察大鼠药动学及对db/db小鼠的降血糖作用。结果：按最优处方制备的微球形态圆整,平均粒径为60 μm,载药量12.5%,体外释药可达1个月。微球在大鼠体内1 h即有药物释放,第8天血药浓度达到峰值C_max（52.96±3.20） ng·mL^-1并持续释放30 d。db/db小鼠的空腹血糖浓度在1个月内有效降低。结论：Notel缓释微球作为1个月长效制剂治疗2型糖尿病（T2DM）具有良好的开发前景。     

利福平丝素蛋白载药微球的制备及性能研究

目的通过测定利福平丝素蛋白微球的载药量、包封率及释放度,考察乳化转速、有机溶剂与丝素蛋白溶液比例,对微球的制备方法进行优化,筛选微球的最佳制备方法。方法采用乳化法制备利福平丝素蛋白微球,以不同转速、有机溶剂与丝素蛋白溶液不同比例分别制备利福平丝素蛋白微球,采用扫描电镜观察微球的形态,用紫外分光光度法测定微球的载药量、包封率及释放度,以形态、载药量、包封率及释放度为指标,筛选微球的最佳制备方法。在此基础上,采用最佳处方制备3批利福平丝素蛋白微球,对微球的形态、粒径、包封率、载药量和释放度进行考察。结果有机溶剂与丝素蛋白溶液体积比为4∶1、转速为200 r·min^-1时所得利福平丝素微球形态均匀,近似球形,载药量和包封率较高,所得载药微球有较好的缓释作用。以最佳处方制得微球载药量为66.1%±0.87%,包封率为87.80%±2.23%。结论有机溶剂与丝素蛋白溶液体积比为4∶1、转速为200 r·min^-1时载药量、包封率和释放度较好,故选择此处方为利福平丝素蛋白微球的最佳制备处方。     

长春西汀s-PLGA长效缓释微球的体内外评价

目的:本研究以星状聚乳酸羟基乙酸共聚物(star poly D,L-lactide-co-glycolide,s-PLGA)为载体制备长春西汀长效缓释微球,对其体内外性质进行评价。方法:采用开环聚合法制备s-PLGA,以此作为载体材料,采用乳化-溶剂挥发法制备长春西汀s-PLGA长效缓释微球(VIN-MS),并对其包封率、粒径和体内外性质进行了考察。结果:本研究制备的VIN-MS的平均粒径为(18±2)μm,包封率为62.20%,载药量为37.43%。扫描电镜观察结果表明,微球外观圆整、均匀,流动性好,分散性好。体外释放结果表明,VIN-MS具有明显的缓释特性,其突释率为6.96%。体内结果表明,VIN-MS制剂体内周期能维持15 d,与长春西汀普通注射剂相比,VIN-MS的曲线下面积(AUC)和平均滞留时间(MRT)分别是普通注射剂的40倍和38倍。结论:长春西汀s-PLGA长效缓释微球的成功制备将有利于脑血管病的治疗。     

Application of Eudragit P-4135F for the delivery of ellagic acid to the rat lower small intestine

Based on the assumption that the delivery of ellagic acid to its site of action would show an antiinflammatory activity in inflammatory bowel disease (IBD), we have prepared microspheres using a new pH-sensitive polymer, Eudragit P-4135F (P-4135F), to deliver ellagic acid to the lower small intestine in rats. The microspheres were spherical in shape and the mean diameters were approximately 100-150 microm. The amount of ellagic acid released from the microspheres decreased by increasing the formulated amount of P-4135F. The release characteristics of ellagic acid were pH-dependent. By considering the factors loading efficiency and microsphere particle size distribution, ellagic acid-2 microspheres (P-4135F/ellagic acid = 1.65) were selected for further investigation. In a dissolution study, more than 95% ellagic acid was released within 0.5 h in pH 7.4 and 8.0 buffers. The release percent of ellagic acid was less than 40% in pH 6.8 and 7.0 and was less than 10% in pH 5.6 and 5.9. To observe the dissolution sites of the microspheres in the rat small intestine fluorescein was formulated in the microspheres as a tracer drug along with ellagic acid (50 mg kg(-1)). After intraduodenal administration of fluorescein-labelled microspheres to rats, the plasma fluorescein level started to increase at 0.5 h, by which time the microspheres had reached the middle part of the ileum. Microspheres started to dissolve within 1.0 h and the peak plasma fluorescein concentration was observed at 3.0 h, when the majority of the administered microspheres were dissolved in the terminal ileum. These results suggested that P-4135F microspheres could deliver ellagic acid to the lower part of the small intestine, and that the released ellagic acid would be distributed into the caecum and the ascending colon.     

Box-Behnken效应面法优化塞来昔布微球制备工艺

目的：制备塞来昔布聚乳酸-羟基乙酸共聚物（PLGA）载药微球,优化其处方和制备工艺,考察其体外释药行为。方法：分别以油相中PLGA浓度、水相PVA浓度和油/水相体积比为考察因素,以包封率为考察指标,采用Box-Behnken效应面法优化塞来昔布微球的处方和工艺;透析袋法评估其体外释放能力。结果：塞来昔布PLGA微球的最佳处方工艺条件为：PLGA浓度75 g·L^-1,水相PVA体积分数1.5%,油/水相体积比1∶30。所制备的微球形态圆整,大小均一,实测包封率为66.1%,与预测值67.3%相比,偏差为1.8%。最优处方体外14 d累积释药56%,体外释放曲线符合Higuchi方程。结论：Box-Behnken效应面法简便可行,可用于优化塞来昔布PLGA微球的制备,微球体外释放具有缓释效果。     

Optimization of prednisolone acetate-loaded chitosan microspheres using a 23 factorial design for preventing restenosis

Prednisolone acetate (PA)-loaded microspheres were prepared by the spray-drying technique using different polymer (1% and 2%) and drug concentrations (10% and 20%). To obtain the optimum formulation, a three-factor two-level (2³) design was employed. The independent variables were polymer molecular weight, polymer concentration, and theoretical drug loading. Responses were the particle size, percentage of encapsulation efficiency, and the t_50% release. The best formulation was prepared with 20% of PA and 1% of chitosan with medium molecular weight showing relative good yield of production (48.0?±?6.7%) and encapsulation efficiency (45.7?±?0.3%), and released the drug at a constant rate in 11 days.     

多西他赛人血白蛋白微球的制备及体外释药性质的评价

目的：通过优选工艺条件制备多西他赛人血白蛋白微球,并考察其体外缓释特性。方法：以人血白蛋白为药物载体,采用乳化-化学交联法制备多西他赛蛋白微球,HPLC测定多西他赛的浓度,通过L₁₆（4⁵）正交设计试验考察药质比、交联剂用量、交联时间、搅拌转速、酸碱度等因素对微球载药量和包封率的影响,利用极差分析和方差分析优选最佳工艺条件;扫描电镜观察微球形态;以累积释药百分率为指标考察微球体外释药特性。结果：最佳工艺条件为药质比为1：7、交联剂用量为2.0 mL、交联时间为1.5 h、搅拌转速为300 r·min^-1、反应介质pH值为7.5;以优化工艺制备的微球在扫描电镜下可见为表面光滑的类球体,平均粒径为36.16 μm,载药量为（11.74±0.26）%,包封率为（65.24±1.24）%,体外释药模式符合Higuchi方程Q=14.34t^1/2+0.21 （r=0.994 5）,48 h体外累积释药百分率为82.8%。结论：本实验通过优化工艺条件,制备完成载药量、包封率和缓释性均较为理想的多西他赛人血蛋白微球。     

叶酸修饰的粉防己碱壳聚糖纳米粒制备工艺的研究

目的:研究叶酸修饰的粉防己碱(tetrandrine, TET)壳聚糖纳米粒(TET/FA-CSO-NPs)的最佳制备工艺并进行质量评价。方法:以离子交联法制备TET/FA-CSO-NPs,通过单因素及正交试验优化处方组成并确定最佳制备工艺,通过形态观察、粒径、载药量及包封率的考察对其进行质量评价。以MTT法分别检测TET和TET/FA-CSO-NPs作用于人肝癌HepG2细胞的增殖抑制作用,并计算半数抑制浓度(IC₅₀)。结果:最佳制备工艺为叶酸-壳聚糖偶联物(FA-CSO)1.50 mg·mL^-1,TPP浓度2.50 mg·mL^-1,载药质量比为1∶1,制备的TET/FA-CSO-NPs粒径为(214.9±2.1) nm, Zeta电位为(35.2±1.3) mV,包封率为(89.49±1.21)%,载药量为(24.41±0.33)%,外观圆整、均匀。FA-CSO空白纳米粒的质量浓度达到800μg·mL^-1时细胞的存活率为(83.08±9.23)%,TET,TET/CSO-NPs和TET/FA-...     

Bupivacaine-loaded biodegradable poly(lactic-co-glycolic) acid microspheres I. Optimization of the drug incorporation into the polymer matrix and modelling of drug release

Bupivacaine has been encapsulated by solvent evaporation method based on O/W emulsion, using poly(DL-lactic-co-glycolic) acid (PLGA) 50:50. The particle size can be controlled by changing stirring rate and polymer concentration. The encapsulation efficiency was affected by polymer concentration and burst effect of bupivacaine released from particles was affected by drug/polymer mass ratio. Orthogonal design was used to optimize the formulation according to drug content, encapsulation efficiency and burst effect. The dissolution profile and release model were evaluated with two different bupivacaine microspheres (bupi-MS) groups including low drug loading (6.41%) and high drug loading (28.92%). It was observed that drug release was affected by drug loading especially the amount of drug crystal attached on surface of bupi-MS. The drug release profile of low drug loaded bupi-MS agreed with Higuchi equation and that of high drug loaded bupi-MS agreed with first order equation.     

Preparation of multi-phase microspheres of poly(D,L-lactic acid) and poly(D,L-lactic-co-glycolic acid) containing a W/O emulsion by a multiple emulsion solvent evaporation technique.

Multi-phase microspheres of poly(D,L-lactic acid) (PLA) or poly(D,L-lactic-co-glycolic acid) (PLGA) containing a water-in-oil (W/O) emulsion were prepared by a multiple emulsion solvent evaporation technique. Acetonitrile was used as the solvent for the polymers and light mineral oil as the dispersion medium for the encapsulation procedure. Process and formulation parameters to optimize the microencapsulation of a W/O emulsion containing water-soluble drugs were investigated. Drug loading efficiencies of 80-100 per cent were obtained under specific preparative conditions. The drug loading efficiency in the microspheres was dependent upon the ratio of the W/O emulsion to polymer and the concentration of surfactant in the mineral oil. Compared to conventional microspheres, in which fine drug particles are homogeneously dispersed in the polymer beads, the multi-phase microspheres permit the higher encapsulation efficiency of water-soluble drugs and eliminate partitioning into the polymer-acetonitrile phase which results in low encapsulation efficiency with conventional solvent evaporation techniques.