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.     

载胰岛素壳聚糖-果胶微球的制备及性能研究

目的以壳聚糖与果胶为载体,三聚磷酸钠、氯化钙为固化剂,制备载胰岛素的壳聚糖-果胶微球,并对微球的基本性质、载药性能及成型机制进行考察。方法采用离子移变胶凝法制备载胰岛素的壳聚糖-果胶微球,采用高效液相色谱法测定包封率,以微球形态、粒径、包封率作为考察指标,进行处方工艺的单因素筛选。用差示扫描量热法与傅里叶变换红外光谱法对微球的成型机制进行初步探讨。初步考察了载胰岛素壳聚糖-果胶微球的体外释药行为。结果胰岛素在0.8～60μg.mL-1内呈现良好的线性,相关系数r=0.999 8。所制备的微球形态圆整,平均粒径为（38.06±3.89）μm,包封率为（44.06±1.63）%。由DSC图谱推断,形成微球时,壳聚糖与果胶之间发生了相互作用。微球的FTIR图谱中未出现新的特征峰,推断在形成微球时,壳聚糖、果胶、胰岛素之间未发生化学反应。初步考察了载胰岛素壳聚糖-果胶微球体外释药呈现明显的缓释作用。结论本法制备工艺简单,重复性好,所制备的胰岛素微球外观圆整,粒径大小分布较均匀,具有明显缓释作用,但包封率不够理想,尚需进一步提高。     

骨炎一号聚乳酸微球的研制

目的 筛选制备骨炎一号聚乳酸微球的最佳工艺。方法 复乳-溶剂挥发法(W／O／W-liquid drying process)制备骨炎一号聚乳酸微球。通过正交实验设计优化骨炙一号聚乳酸微球制备工艺，用电子显微镜观察微球表面形态，差示扫描热分析确证含药微球的形成，及对所制备微球的平均粒径、载药量、包封率、工艺重现性进行了研究。结果骨炎一号聚乳酸微球的形态圆整，且药物确已被包裹在微球中，而非机械混合，微球的平均粒径为8．59μm，粒径在1～12μm左右的占总数的90%以上，载药量为48．39%，包封率为19．32％。结论得到了骨炎一号聚乳酸微球较满意的制备工艺。     

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。     

阿霉素载药栓塞微球的制备和性能表征

目的：研究离子交换型阿霉素载药透明质酸栓塞微球（DHAMs）的制备方法及性能表征。方法：采用油包水（W/O）乳化交联法,以改性透明质酸（HA）为载药基质,通过离子交换原理制备载阿霉素的透明质酸栓塞微球。采用光学显微镜、扫描电子显微镜观察表面形态,考察粒径和溶胀率;采用恒温摇床模拟体内环境初步测定透明质酸微球降解率;采用紫外分光光度法测定DHAMs载药量、包封率和体外释放率;采用傅里叶变换红外光谱（FT-IR）和粉末X射线衍射法（PXRD）对DHAMs进行表征。结果：透明质酸微球形态圆整、表面光滑,平均粒径为（111.83 ± 12.21）μm,溶胀率为201.81%;微球56 d体外降解率为34.31%;微球载药量和包封率分别为（22.09% ± 0.05%）和（99.41% ± 0.21%）,且72 h累计释放量可达50%;FT-IR和PXRD分析显示,阿霉素在微球中以无定形形式存在。结论：阿霉素透明质酸微球有较好的载药性能,理化性能良好,具有动脉化疗栓塞的应用前景。     

罗哌卡因-醋酸地塞米松PLGA微球的制备及体外释药特性研究

目的 制备罗哌卡因 醋酸地塞米松聚乳酸羟基乙酸共聚物（PLGA）微球（简称微球）并研究其体外释药特性。方法以PLGA为载体,采用W1/O/W2双重乳化 溶剂挥发法制备微球,研究实验过程中有机相PLGA浓度、外水相/有机相体积比、内水相体积、外水相聚乙烯醇（PVA）浓度几项因素变化对罗哌卡因 醋酸地塞米松PLGA微球粒径、表面形态﹑载药量﹑包封率和突释行为的影响。结果有机相PLGA浓度在制备微球的过程中是一个关键性因素。随着PLGA浓度增加,微球粒径增大,载药量﹑包封率明显提高,突释降低;外水相/有机相体积比增大,微球粒径增大, 载药量﹑包封率明显提高,微球表面更加光滑﹑微孔减少,突释降低;随着内水相体积增加使得微球表面的微孔明显增多,突释增加,载药量﹑包封率降低;当外水相PVA浓度由0.5%增加到2%,微球粒径变小,突释效应增加。通过优化条件制备的微球形状为球形,外观光滑圆整,粒径分布均匀,其中＞90%分布在20～70 μm。罗哌卡因载药量（7.48±0.33）%,包封率（70.97±2.36）%;醋酸地塞米松载药量（1.52±0.16）%,包封率（57.30±1.17）%。结论采用W1/O/W2双重乳化 溶剂挥发法成功制备罗哌卡因加醋酸地塞米松PLGA微球;以优化工艺制备的微球,在体外具有明显的缓释行为,释药曲线呈典型S形三阶段模式。     

长春西汀聚乳酸-聚乙醇酸缓释微球的研制

目的:制备长春西汀聚乳酸-聚乙醇酸(PLGA)缓释微球,并研究其药剂学性质。方法:采用改良O/W乳化-溶剂挥发法制备微球,以PLGA浓度、理论载药量、有机相与分散介质的比例和分散介质中明胶的浓度为4因素,每个因素选定3个水平,按L9(34)的正交设计方案,以载药量、包封率和粒径分布为指标,优化处方。用扫描电镜观察微球的形态,用光学显微镜观察并计算微球的粒径分布,用差示扫描量热(DSC)法研究药物在载体中的分散状态,用紫外分光光度法检测微球中长春西汀含量并计算载药量和包封率,用动态透析释药法进行微球的体外释放研究。结果:最佳处方为PLGA浓度16%,理论载药量20%,有机相与分散介质的比例1:10,分散介质中明胶的浓度1%;制备的长春西汀PLGA缓释微球的形态圆整、光滑,粒径分布均匀,平均粒径为(10.0±0.18)μm(n=500),DSC法分析药物确已被包裹于微球中,载药量为(18.46±0.26)%,包封率为(91.30±0.98)%(n=3),24h累积释药率约为18%。结论:长春西汀PLGA缓释微球制备工艺稳定,质量符合药剂学要求,缓释性好。     

红霉素聚乳酸微球制备工艺的研究

目的 :通过正交设计筛选出制备红霉素聚乳酸微球的最佳工艺。方法 :用正交实验设计优化红霉素聚乳酸微球制备工艺 ,用扫描电子显微镜观察微球表面形态 ,差示扫描热分析确证含药微球的形成 ,及所制备的红霉素聚乳酸微球的平均粒径、粒度分布 载药量 包封率 工艺重现性进行了研究。结果 :红霉素聚乳酸微球的形态圆整 ,且药物确已被包裹在微球中 ,而非机械混合 ,微球的平均粒径为 10 .98± 0 .15mm ,粒径在 5～ 2 0mm占总数的 94 %以上 ,载药量为 2 4 .16 %± 0 .5 1,包封率为 6 3.5 4 %± 0 .5 8,最佳工艺条件重现性良好。结论 :本研究获得了制备红霉素聚乳酸微球较满意的工艺     

环丙沙星聚乳酸微球的制备、性状和体外释药性能的研究

目的采用乳化-溶剂蒸发法制备环丙沙星聚乳酸微球,并对其性状进行考察.方法通过正交设计试验筛选其最佳制备工艺, 用电子显微镜观察微球表面形态, 差示扫描热分析确证含药微球的形成, 并对微球的平均粒径、载药量、包封率、体外释药性能进行了研究.结果环丙沙星聚乳酸微球的形态圆整, 且药物确已被包裹在微球中, 微球的平均粒径为280.80±0.15 μm, 粒径在250-390 μm之间的占总数的90%以上. 包封率为68.5%±0.58, 载药量为34.1%±0.51,环丙沙星微球的体外释药情况为53.2小时的累积释药量为84.0%,T1/2为31.9 h, Higuchi方程为Q=-0.004 3 0.003 9 t1/2,r=0.994 1.结论本研究获得了较满意的制备环丙沙星聚乳酸微球的工艺, 且微球的体外释药性能具有明显的缓释效果.     

肺靶向多西紫杉醇壳聚糖微球的制备与工艺优化

目的：研制肺靶向多西紫杉醇壳聚糖微球,并对处方工艺进行筛选。方法：以壳聚糖为载体,采用乳化-化学交联法制备多西紫杉醇壳聚糖微球。在单因素考察的基础上,利用正交试验设计优化微球制备工艺,采用HPLC法测定微球的载药量与包封产率。结果：制得的微球显微观察形态圆整、表面光滑,无粘连;平均粒径为（8．63±0．27）μm,粒径7—12μm的微球平均占总数的83．5％,载药量为（25．01±1．80）％,包封产率为（85．54±2．21）％。结论：筛选的最佳处方工艺制备的微球粒径大小适宜,可满足肺靶向微球的要求;该制剂有可能成为临床肺部肿瘤治疗的一种靶向制剂。     

Preparation and evaluation of alginate-chitosan microspheres for oral delivery of insulin

The alginate-chitosan microspheres with narrow size distribution were prepared by membrane emulsification technique in combination with ion (Ca²⁺) and polymer (chitosan) solidification. The preparation procedure was observed, and the physical properties (particle size distribution, surface morphology, chitosan distribution, zeta potential) of the microspheres were characterized. Subsequently, the microspheres were employed to load model peptide of insulin. The effect of loading ways on the loading efficiency and immunological activity of insulin were investigated. It was shown that the higher loading efficiency (56.7%) and remarkable activity maintenance (99.4%) were obtained when the insulin was loaded during the chitosan solidification process (Method B). Afterward, the release profile in vitro for the optimal insulin-loaded microspheres was investigated. Under the pH conditions of gastrointestinal environment, only 32% of insulin released during the simulated transit time of drug (2 h in the stomach and 4 h in the intestinal). While under the pH condition of blood environment, insulin release was stable and sustained for a long time (14 days). Furthermore, the chemical stability of insulin released from the microspheres was well preserved after they were treated with the simulated gastric fluid containing pepsin for 2 h. Finally, the blood glucose level of diabetic rats could be effectively reduced and stably kept for a long time (∼60 h) after oral administration of the insulin-loaded alginate-chitosan microspheres. Therefore, the alginate-chitosan microspheres were found to be promising vectors showing a good efficiency in oral administration of protein or peptide drugs.     

正交试验优选姜黄素明胶微球的处方工艺

目的:优选姜黄素明胶微球的最佳处方工艺。方法:以明胶浓度、油水比例、乳化时间为考察因素,以载药量、包封率、微球粒径为评价指标,以明胶为载体,采用正交试验优选乳化交联法制备姜黄素明胶微球的处方工艺。结果:优选的处方工艺要求油水比为1:5,明胶浓度为25%,乳化时间为30min。结论:该处方工艺稳定、可行,重现性好,可为姜黄素明胶微球的后续研究提供理论依据。     

口服胰岛素羧甲基壳聚糖纳米粒的制备及评价

目的:研制一种生物利用度高且具有缓释作用的口服胰岛素制剂。方法:通过钙离子交联制备羧甲基壳聚糖纳米粒,采用正交试验优化纳米粒制备条件,以透射电镜观察纳米粒形态,激光粒度分析仪测定粒度,高效液相色谱法测定纳米粒包封率和载药量,并对胰岛素的体外释放性能进行考察。结果:优化工艺制备的纳米粒外观形态圆整,平均粒径为(256.1±11.2)nm,包封率为(45±0.41)%,载药量为(17.2±0.33)%,药理相对生物利用度为14.71%。结论:口服载胰岛素羧甲基壳聚糖纳米粒具有降血糖作用和显著的缓释作用,药理相对生物利用度高。     

Application of a novel approach to prepare biodegradable polylactic-co-glycolic acid microspheres: surface liquid spraying

A novel approach which had foreground of industrialization, surface liquid spraying, was studied in this paper to prepare biodegradable polylactic-co-glycolic acid (PLGA) microspheres for controlled release drug delivery system. To compare with the normal methods, the microspheres prepared by this approach were characterized by particle size distribution and photograph of microscope. The relationship between the particle size and the instrument parameters of novel method was set up for the first time. The central composite design (CCD) was applied to study the main effects and interactions of three instrument factors on preparation of microspheres. The particle size of microspheres was below 200 mum and the shape of microspheres was spherical in nature evidenced by microscope photographs. Vinpocetine was used as the model drug to prepare the vinpocetine PLGA microspheres (VIN-PLGA-MS), and then drug loading, entrapment efficiency, scanning electron microscopy (SEM), Differential Scanning Calorimetry (DSC) and in vitro drug release behavior were examined. The results indicated that the drug loading and entrapment efficiency were increased using the novel method. The drug released slowly more than 30 days. The release behavior was fit for four kinds of kinetic model. The result indicated that release behavior was fitted by Zero-order kinetic model before release 72 hours, and was fitted with First-order kinetic model after release 72 hours. The novel method developed in our paper can give a promising way for industrialization, and the foreground was also proved by the scale-up batch experiment.     

Effects of formulation variables and characterization of guaifenesin wax microspheres for controlled release

Sustained-release wax microspheres of guaifenesin, a highly water-soluble drug, were prepared by the hydrophobic congealable disperse method using a salting-out procedure. The effects of formulation variables on the loading efficiency, particle properties, and in-vitro drug release from the microspheres were determined. The type of dispersant, the amount of wetting agent, and initial stirring time used affected the loading efficiency, while the volume of external phase and emulsification speed affected the particle size of the microspheres to a greater extent. The crystal properties of the drug in the wax matrix and the morphology of the microspheres were studied by differential scanning calorimetry (DSC), powder x-ray diffraction (XRD), and scanning electron microscopy (SEM). The DSC thermograms of the microspheres showed that the drug lost its crystallinity during the microencapsulation process, which was further confirmed by the XRD data. The electron micrographs of the drug-loaded microspheres showed well-formed spherical particles with a rough exterior.     

硝苯地平生物黏附微球的制备及释药机制研究

目的:制备硝苯地平生物黏附微球并考察其体外释药情况。方法:在单因素考察的基础上应用正交设计筛选硝苯地平生物黏附微球的最佳处方,因素为加热温度、聚乙烯醇(PVA)用量、司盘浓度和戊二醛用量,评价指标为累积释药率;考察优化处方所制微球的质量指标如体外黏附力和累积释药率等,研究其释药机制。结果:优化处方工艺为:加热温度60℃、PVA用量0.6 g、司盘浓度5%、戊二醛用量0.6 mL;优化处方所制微球体外黏附力较高,平均载药量约为15%,包封率约为85%,平均粒径约为20μm;微球可持续24 h释药,释药符合Higuchi方程,释药机制符合非Fick扩散机制,即以溶蚀和扩散2种模式释放。结论:硝苯地平生物黏附微球制备工艺简单,具有较好的体外黏附性能和缓释效果。     

星点设计-效应面法优化普萘洛尔传递体的处方工艺

目的应用星点设计-效应面法优化普萘洛尔传递体的处方工艺。方法采用硫酸铵梯度法制备普萘洛尔传递体。将药物/磷脂摩尔比、Span-80/磷脂摩尔比、探头超声时间作为考察因素,以包封率、载药量、平均粒径及变形性指数为效应指标,求算总评"归一值"并采用Design-Expert 8.0软件进行效应面法优化,确定最佳处方工艺并进行验证。结果确定最优制备工艺为:药物/磷脂摩尔比19.83%、Span-80/磷脂摩尔比21.08%、探头超声时间10.29 min,以该处方工艺制备所得传递体的包封率、载药量、平均粒径及变形性指数分别为76.63%,4.80%,52.82 nm,20.83,且实测值与预测值的偏差均较小。结论星点设计-效应面法适用于普萘洛尔传递体的处方工艺优化,优化所得处方工艺稳定、可行。     

Influence of magnesium stearate on the physicochemical and pharmacodynamic characteristics of insulin-loaded Eudragit entrapped mucoadhesive microspheres

Abstract

Effective oral insulin delivery has remained a challenge to the pharmaceutical industry. This study was designed to evaluate the effect of magnesium stearate on the properties of insulin-loaded Eudragit® RL 100 entrapped mucoadhesive microspheres. Microspheres containing Eudragit® RL 100, insulin, and varying concentrations of magnesium stearate (agglomeration-preventing agent) were prepared by emulsification-coacervation method and characterized with respect to differential scanning calorimetry (DSC), morphology, particle size, loading efficiency, mucoadhesive and micromeritics properties. The in vitro release of insulin from the microspheres was performed in simulated intestinal fluid (SIF, pH 7.2) while the in vivo hypoglycemic effect was investigated by monitoring the plasma glucose level of the alloxan-induced diabetic rats after oral administration. Stable, spherical, brownish, mucoadhesive, discrete and free flowing insulin-loaded microspheres were formed. While the average particle size and mucoadhesiveness of the microspheres increased with an increase in the proportion of magnesium stearate, loading efficiency generally decreased. After 12?h, microspheres prepared with Eudragit® RL 100: magnesium stearate ratios of 15:1, 15:2, 15:3 and 15:4 released 68.20?±?1.57, 79.40?±?1.52, 76.60?±?1.93 and 70.00?±?1.00 (%) of insulin, respectively. Reduction in the blood glucose level for the subcutaneously (sc) administered insulin was significantly (p?≤?0.05) higher than for most of the formulations. However, the blood glucose reduction effect produced by the orally administered insulin-loaded microspheres prepared with four parts of magnesium stearate and fifteen parts of Eudragit® RL 100 after 12?h was equal to that produced by subcutaneously administered insulin solution. The results of this study can suggest that this carrier system could be an alternative for the delivery of insulin.     

Chitosan microspheres of aceclofenac: In vitro and in vivo evaluation

The objective of this investigation was to achieve controlled drug release of Aceclofenac (ACE) microspheres and to minimize local side-effects in the gastrointestinal tract (GIT). Sustained release chitosan microspheres containing ACE were prepared using double-emulsion solvent evaporation method (O/W/O). Chitosan microspheres were prepared by varying drug to polymer ratio (1:3, 1:4, 1:5 and 1:6). Microspheres were characterized for morphology, swelling behavior, mucoadhesive properties, FTIR and DSC study, drug loading efficiency, in vitro release, release kinetics, and in vivo study was performed on rat model. ACE-loaded microspheres were successfully prepared having production yield, 57–70% w/w. Drug encapsulation efficiency was ranging from 53–72% w/w, Scanning electron microscopy (SEM) revealed particle size of microspheres was between 39 and 55 μm. FTIR spectra and DSC thermograms demonstrated no interaction between drug and polymer. The in vitro release profiles of drug from chitosan microspheres showed sustained-release pattern of the drug in phosphate buffer, pH 6.8. In vitro release data showed correlation (r² > 0.98), good fit with Higuchi/Korsmeyer-Peppas models, and exhibited Fickian diffusion. ACE microspheres demonstrated controlled delivery of aceclofenac and apparently, no G.I.T. erosion was noticed.