尼索地平微球在家兔体内释药的研究

目的:研究尼索地平微球在家兔体内的释药行为。方法:建立检测体内尼索地平血药浓度的高效液相色谱法,研究家兔肌注自制微球后的血药浓度经时变化情况。结果:微球在第1天有明显的突释效应,此后18 d内每天的血药浓度维持在4 μg·L~(-1)左右,波动范围较小。结论:微球在体内有良好的控释作用。     

反溶剂冻干法制备微粉化间尼索地平

采用反溶剂冻干法制备微粉化间尼索地平,以粒径为指标,优化微粉化条件.分别采用扫描电镜(SEM)、红外光谱仪(IR)、差热分析仪(DSC)和X射线衍射仪(XRD)对产品进行了分析与表征;微粉化后的药物溶解度和溶出速率显著提高.     

干扰素α-2b复合物PLGA微球的制备及影响因素

制备了干扰素-α（IFN-α）-锌离子复合物微粉，再用部分无水的乳化-溶剂挥发法制成PLGA微球。通过考察制备工艺中影响微球的因素，筛选处方和工艺。结果表明，IFN-α-锌离子复合物微粉平均粒径为0.3μm。按优化处方制得的微球表面光滑、圆整，平均粒径41μm，载药量0．79％，包封率79％，突释28％。复合物和微球制备工艺对IFN-μ生物活性无明显影响。     

水溶性药物聚丙交酯微球的研究

目的考察内相乙醇加入量及其他制备因素对聚丙交酯微球性质的影响。方法以水略溶性药物氟尿嘧啶和水溶性药物地基米松磷酸钠为模型药物，乳化／溶剂挥发法制备微球。维持其他制备条件不变，改变内相乙醇加入量、理论载药量、聚丙交酯浓度、溶剂挥发时间及聚丙交酯分子质量，考察微球载药量、包封率、粒径和释放的影响。结果随着内相乙醇加入量的增多，微球形成加快，微球的粒径减小，模型药物的载药量及包封率略有升高，但乙醇加入量太多时载药量及包封率均明显降低。内相聚丙交酯浓度越大，形成的微球粒径越大，载药量及包封率也愈大。理论载药量对微球粒径影响不大，地基米松磷酸钠的包封率随理论载药量的增加而减小，而氟尿嘧啶为理论载药量为15％时，包封率最大。溶剂挥发时间在0．5～3h，微球的性质无明显变化。分子质量愈小，微球的粒径愈小，载药量及包封率亦随之减小。结论内相中加入一定量乙醇可以提高药物的包封率，并减少有毒含氯溶剂的用量。     

单唾液酸四己糖神经节苷脂的PLGA微球的制备

目的研究W/O/W型乳化溶剂挥发法制备单唾液酸四己糖神经节苷脂（GM-1）的乳酸/羟基醋酸共聚物（PLGA）微球的优化工艺。方法以微球形态、粒径、载药量和包封率为检测指标，通过单因素法筛选影响微球制备工艺的10种因素，优化GM-1的PLGA微球的制备工艺。结果在优化条件下制备的微球形态规则，粒径约(19.3±8.5)μm，载药量＞4.7 %。结论该制备工艺合理，为制备GM-1的PLGA微球提供了理论依据。     

长效镇痛控释微球的制备新技术

疼痛是机体对体内外环境伤害性刺激的一种保护性反应，具有实质的或潜在的组织损伤。疼痛的发生具有普遍性、经常性、严重性的特征。疼痛的不快感，肉体和精神上的痛楚迫使患者寻医找药，疼痛及其治疗成为全球关注、重视和研究的热点。     

间尼索地平与尼索地平对清醒兔血流动力学和局部血流量的影响

应用放射性生物微球技术观察间尼索地平(m-Nis)和尼索地平(Nis)对清醒兔血流动力学和局部血流量的影响。m-Nis 1μg/kg·min~(-1)×10min iv显著增加清醒兔CO、CI、SV和LVSW;等剂量Nis增加CO及CI不显著;两药对清醒兔MABP、HR和脑、心、肾、脾等局部血流量影响相似,对这些器官的血流分布及心输出量分布无明显影响。     

尼索地平自微乳制剂稳定性的影响因素

目的：研究影响尼索地平自微乳制剂稳定性的因素。方法：以温度、稀释倍数、稀释递质种类、絮凝剂及反絮凝剂为主要影响因素，采用测定微乳粒子大小及其分布、Zeta电位进行综合评价。结果：本自微乳制剂对稀释倍数、稀释递质种类、絮凝剂及反絮凝剂敏感，但对温度不敏感，且粒径稳定。结论：本自微乳制剂质量稳定，但稀释后的微乳稳定性下降。     

乳化溶剂挥发法在微球制备中的应用

微球(microspheres)是药物溶解或分散于高分子材料中形成的微小球状实体,一般制备成混悬剂供注射或口服用。用于制备缓控释微球的可生物降解高分子材料中,以聚乳酸(polylactic acid,PLA)及其共聚物为代表的羟基酸聚合物应用最广。制备药物缓释微球的方法很多,包括乳化溶剂挥发法、相分离法、乳化溶剂萃取法、喷雾干燥法、熔融法等,其中乳化溶剂挥发法最为常用。笔者对乳化溶剂挥发法制备微球的方法及制备过程中影响微球质量的因素进行综述。1乳化溶剂挥发法主要包括O/W乳化法、O1/O2乳化法、复乳-液中干燥法。O/W乳化法适合脂溶性药物微…     

The Production of Uniformly Sized Polymer Microspheres

Pharmaceutical Research -     

替莫唑胺乳酸-羟基乙酸共聚物微球的制备及表征

采用乳化-溶剂挥发法制备替莫唑胺微球,考察了制备工艺中影响微球粒径、载药量和包封率的主要因素,筛选处方工艺.按优化工艺制得的微球形态圆整,表面光滑,平均粒径62.2μm,载药量7.5%,包封率83.5%,体外试验表明该载药微球有明显的缓释效果.     

GM-1PLGA肌注微球的制备及其体外释药评价

目的 研究以聚乳酸羟基乙酸共聚物为囊材,制备长效缓释的单唾液酸四己糖神经节苷脂微球制剂.方法运用复乳溶剂挥发法,考虑多个条件对制备工艺的影响,并采用正交设计对处方进行优化.测定微球的载药量、包封率和释放曲线.结果制备得到的GM-1微球粒径大小均匀,球形致密圆整,微球粒径为(8.2±6.0)μm,载药量和包封率分别为18...     

Study of the Influence of Several Stabilizing Agents on the Entrapment and In Vitro Release of pBC 264 from Poly(Lactide-Co-Glycolide) Microspheres Prepared by a W/O/W Solvent Evaporation Method

Pharmaceutical Research -     

Microencapsulation of ovalbumin in poly(lactide-co-glycolide) by an oil-in-oil (o/o) solvent evaporation method

Abstract

The objective of this study was to produce biodegradable poly(lactide-co-glycolide) (PLGA; 50/50) microspheres by an oil-in-oil (o/o) solvent evaporation method to prolong the in vitro release of ovalbumin (OVA) as a model protein. The effects, on loading efficiency, microsphere yield, morphology and drug release, of two dispersing agents, aluminum tristearate and Span 80, in mineral oil were examined. PLGA 50/50 microspheres containing OVA powder (sieved through a 53 μm mesh) were prepared using an o/o solvent evaporation method. When aluminum tristearate was employed as a dispersing agent, the loading efficiency and yield of OVA had maximum values of 89 and 72% at 0·15% (w/v) aluminum tristearate, respectively. Morphology studies suggested that the obtained microspheres were spherical, and had a smooth surface. The diameters of the microspheres ranged between 100 and 200 μm. The loading efficiency, or yield, for microspheres decreased significantly above or below 0·15% (w/v) aluminum tristearate, and microspheres wkh irregular shapes were observed. The minimum sedimentation volume ratio (F) was obtained at a dispersity of carbon black particles in ethanol containing 0·15% (w/v) aluminum tristearate by a sedimentation study, and the cloudy supernatant suggested a defiocculated suspension. However, on the contrary, when Span 80 was added into the mineral oil as a dispersing agent, the concentration of Span 80 had little or no effect on the characteristics of the prepared microspheres. Drug loadings (60–70%) were obtained within the Span 80 concentrations employed in the present study (0·05–1·0% (w/v)). The yields were also in the same levels. The microspheres prepared in mineral oil containing Span 80 had an average diameter less than 50 μm in all cases. Sustained-release characteristics were demonstrated for PLGA microspheres prepared in mineral oil containing aluminum tristearate as a dispersing agent, even though a burst release at the initial phase was observed. This initial burst release from PLGA microspheres was reduced to some extent by micronization of the OVA powder using a planetary-type ball mill. However, PLGA microspheres prepared in mineral oil containing Span 80 as a dispersing agent, exhibited a large initial burst release. This burst release seems to be due to the smaller size of microspheres and the OVA powder adhering to the surface of PLGA microspheres (confirmed by scanning electron microscope (SEM) study).     

Preparation and characterization of biodegradable urea-loaded microparticles as an approach for transdermal delivery

This work describes the formulation and characterization of urea-loaded microspheres prepared using various polymers such as ethyl cellulose (EC), cellulose acetate phthalate (CAP) and poly (D,L-lactic-co-glycolic acid) (PLGA), along with the utilization of a solvent evaporation technique. The effect of various formulation parameters (i.e. polymer type and concentration, vehicle type, polymer solution/vehicle volume ratio, drug/polymer ratio, homogenizer and stirrer speed, sonication time and speed, type of washing solution, drying and separation method) on the characteristics of microspheres was also evaluated. Results obtained indicated that, in the presence of urea, highest rate of EC microsphere production could be obtained at a drug/polymer ratio of 1:2 and a polymer solution/vehicle volume ratio of 1:50. In some cases, crystallization of urea was observed during the encapsulation process using cellulose derivative polymers. CAP microparticles showed a rough and tortuous surface while EC microparticles had a wider range of particle size. However, with the PLGA polymer, much better desired microparticles with a smaller size range of 1–3?µm were obtained. In general, PLGA microspheres were spherical in shape and possessed smooth surfaces with less pores in comparison with those obtained by the other polymers. The yield of particle production and the extent of urea encapsulation in PLGA particles were measured to be 68.87%?±?5.3 and 40.5%?±?3.4, respectively. The release study from PLGA microspheres revealed that up to 70% of the drug was released within a few days, through a four-stage release pattern.     

Sophoridine-loaded PLGA microspheres for lung targeting: preparation,in vitro,and in vivo evaluation

Lung-targeting sophoridine-loaded poly(lactide-co-glycolide) (PLGA) microspheres were constructed by a simple oil-in-oil emulsion-solvent evaporation method. The obtained microspheres were systematically studied on their morphology, size distribution, drug loading, encapsulation efficiency, in vitro release profile, and biodistribution in rats. The drug-loaded microparticles showed as tiny spheres under SEM and had an average size of 17?μm with 90% of the microspheres ranging from 12 to 24?μm. The drug loading and encapsulation efficiency were 65% and 6.5%, respectively. The in vitro drug release behavior of microspheres exhibited an initial burst of 16.6% at 4?h and a sustained-release period of 14 days. Drug concentration in lung tissue of rats was 220.10?μg/g for microspheres and 6.77?μg/g for solution after intraveneous injection for 30?min, respectively. And the microsphere formulation showed a significantly higher drug level in lung tissue than in other major organs and blood samples for 12 days. These results demonstrated that the obtained PLGA microspheres could potentially improve the treatment efficacy of sophoridine against lung cancer.     

氟尿嘧啶微球的制备工艺

分别采用o／o型和o／w型乳化挥发法及喷雾干燥法制备氟尿嘧啶聚乳酸微球。3种方法制得的微球外观均圆整光滑。其中，o／o型乳化挥发法制得的微球实际载药量小于2．0％，不适宜制备本品；另两种方法制备的微球载药量分别为10．25％和26．18％，平均粒径分别为49．6μm和1.09μm，体外释药t1/2分别为134h和8h。结果表明，后二法制备的微球缓释效果明显。     

高分子材料对卡铂-乳酸/羟基乙酸共聚物微球体外性质的影响

目的:制备卡铂-乳酸／羟基乙酸共聚物(poly(lactic-co-glycolic acid),PLGA)微球,比较不同PLGA所得微球的体外释药特点。方法:采用乳化-溶剂挥发法制备卡铂-PLGA微球,显微镜下测定微球的粒径和粒径分布。采用电感耦合等离子体质谱(ICP-MS)测定微球含药量,计算包封率,考察微球体外释药行为。结果:PLGA来源和规格不同,对微球的形态、粒径、载药量和包封率没有明显影响,所得微球球形较好,平均粒径为38-54μm,含药量为6．4-7．2μg·mg-1,包封率16．3％-22．7％。药物体外释放行为随PLGA不同而有很大差异,PLGA 50／50微球突释快,突释率高。PLGA(50／50,η=0．18)和PLGA(50／50,η=0．53)的微球2 h药物突释率分别为55．06％和83．10％;PLGA(75／25,η=0．19)和PLGA(75／25,η=0.30)的微球12 h药物突释率分别为38．43％和44．04％。缓慢释放期PLGA(50／50,η=0．53)微球释药符合零级释放模型,其他3种材料的微球符合Higuchi释放方程,PLGA (50／50,η=0．18)和PLGA(75／25,η=0．19)微球体外较好地控制药物释放,缓释期药物释放速度常数分别为1．18和2.40 h-1/2。结论:PLGA来源和组成不同,制备的微球体外释药行为差异较大。PLGA(75／25,η=0．19)微球体外较好地控制卡铂的释放。     

Dose and Load Studies for Subcutaneous and Oral Delivery of Poly(lactide-co-glycolide) Microspheres Containing Ovalbumin

Poly(lactide-co-glycolide) microspheres containing different loads of OVA (0.05, 0.1, 0.5 and 1.0% w/w) were manufactured by a w/o/w emulsion/solvent evaporation method. Low load efficiencies of less than 20% were observed. Normal size distributions with mean volume diameters ranging from 3.7 to 4.7 µm were obtained for different batches. The in vitro release of OVA from different loaded microspheres showed an expected burst release with all batches. The in vivo dose study (1, 10, 25, 50 µg of OVA) was performed by subcutaneous and oral inoculation in mice by single (0 week) or double (0 and 3 weeks) administration of PLGA 50/50 microspheres containing 0.1% OVA. Subcutaneous administration showed an immune response (serum Ig levels by ELISA) statistically (Fishers paired t-test; P < 0.05) above OVA saline negative controls at 3, 6 and 12 weeks after administration. Oral administration of microspheres produced statistically higher systemic immune responses at the higher doses. Single and double inoculation orally and subcutaneously produced similar serum antibody levels. The in vivo load study was performed by subcutaneous and oral administration to mice of 25 µg OVA contained in various loaded (0.05, 0.1, 0.5 and 1.0% w/w) microspheres. Serum immune responses at 3, 6, and 12 weeks after inoculation were statistically above OVA saline controls and were inversely proportional to the OVA load using either route. This observation suggested a relationship between the number of microspheres delivered and the in vivo serum response. Single subcutaneous administration of 0.05 or 0.1% OVA loaded PLGA 50/50 microspheres induced larger immune responses compared with complete Freunds adjuvant.