超临界流体技术制备吗啡/聚乳酸-聚乙二醇共聚物缓释微球

以L-聚乳酸-聚乙二醇三嵌段共聚物(PLLA-PEG-PLLA)为载体材料,通过超临界流体强制溶液分散技术制备吗啡/聚乳酸-聚乙二醇共聚物(MF/PLLA-PEG-PLLA)的复合微球,考察了PEG分子量的变化对微球性能的影响。通过表面形貌,粒径及粒径分布,载药量,包封率及释放性能来表征复合微球的各项性能;利用气相色谱法测定二氯甲烷和甲醇的残留量;通过溶血实验来评价复合微球的血液相容性。实验表明,所制备的复合微球呈球形或类球形形貌,平均粒径在1.99～6.20μm之间,载药量达到17.92%,包封率最高可至69.57%,复合微球的药物释放呈先突释后缓释的释药模式;二氯甲烷和甲醇的残留量分别为0.0076%和0.0016%;微球溶血率<1%,远小于国家标准5%,证明复合微球具有较好的血液相容性。     

明胶微球/磷酸镁基骨水泥复合药物缓释体系的构建

采用乳化交联法制备出粒径主要分布在100~300 μm的载药明胶微球, 分析了交联剂含量、药物含量和转速对载药率和包封率的影响及药物含量和转速对微球粒径的影响。对载药明胶微球与磷酸镁基骨水泥进行复合, 探讨微球降解过程中复合体系孔隙率的变化及其在体外药物释放的规律, 以期获得一种具有药物缓释性能的多孔磷酸镁基复合骨水泥。结果表明, 随着葡萄糖浓度增加, 载药率和包封率先上升再下降; 随着药物含量的增加, 载药率保持上升, 包封率先上升后下降; 随着转速增加, 载药率和包封率均下降。综合分析, 在转速为400 r/min、葡萄糖浓度为0.5 g/mL、药物与明胶质量比为1:2的条件下制备的载药明胶微球载药量较高, 且粒径合适。将复合不同比例该载药微球的磷酸镁基骨水泥浸泡在Tris-HCl缓冲溶液中进行体外药物释放研究, 结果表明: 在释放前期(0~10 h)药物释放速率较快, 之后药物释放明显减缓。7 d后, 微球几乎降解完全, 药物释放率达到60%~89%, 达到了一定的药物缓释效果。     

载异烟肼聚己内酯微球的制备及其性质研究

采用O/O溶剂挥发法制备载异烟肼聚己内酯微球。系统考察了活性剂浓度、内外油相体积、投药量对微球粒径、载药量和包封率的影响。结合内外油相初始粘度分析载药微球成球性,用IR、XRD、SEM对微球化学结构、结晶状态和表面形貌进行表征。通过优化得到平均粒径为28.73μm、载药量为2.36%、包封率为49.58%、外观圆整、表面多孔的载药微球。与O/W溶剂挥发法制备微球对比表明,O/O法有效地提高了载异烟肼聚己内酯微球载药量与包封率,是包覆亲水性小分子药物的可行方法,该载药微球可望用于骨和关节结核病的缓释治疗。     

超临界CO2抗溶剂法制备紫杉醇缓释微球

采用超临界流体强制分散溶液技术,以D,L-聚乳酸和D,L-聚乳酸-聚乙二醇共聚物为载体材料,分别制备了紫杉醇缓释微球.通过扫描电镜、激光粒度仪检测微球外形及粒径分布;紫外吸光度法测量其载药量和包封率,恒温振荡透析法检测药物的体外释放性能;MTT法检测载药微球对Hela细胞的抑制作用.实验表明,两种载体的缓释微球球形度均较好,表面光滑,平均粒径较小,且粒径分布较窄.以聚乳酸和共聚物为载体的缓释微球载药量分别为5.4%±0.3%和5.3%±0.4%,包封率分别为51%±3%和45%±3%;药物释放呈缓释模式,共聚物载药微球药物释放速率较快.MTT法检测结果表明,载药微球对Hela细胞的增殖有明显抑制,共聚物载药微球对细胞增殖抑制更为明显.     

BSA-PLGA微球的优化制备及特性

目的:优化BSA-PLGA微球制备工艺,并对其包封率、形态、体外释放药物及微球包裹前后BSA的稳定性进行评价。方法:以PLGA为载体,采用复乳溶剂挥发法制备BSA-PLGA微球。Micro BCA法测定微球的包封率和载药量,扫描电子显微镜观察微球的形态,激光粒度仪测定粒度及分布,聚丙烯酰胺凝胶电泳(SDS-PAGE)研究微球包裹前后BSA分子结构的完整性,同时考察体外释药性能。结果:根据优化工艺制备的微球外观圆整,平均粒径(2275.8±256.9)nm,包封率(82.59±2.92)%,载药量(13.76±0.49)×10-2%,包裹前后BSA结构稳定,体外释放28天以上,释放曲线符合Higuchi方程。结论:本研究获得了较优化的BSA-PLGA微球制备工艺,所制备的微球具有较高的包封率和明显的缓释效果。     

原位共沉淀法制备载药Fe3O4/壳聚糖磁性复合微球及其体外药物释放行为

以核黄素为药物模型,采用原位共沉淀法制备了一种载药Fe₃O₄/壳聚糖复合微球。傅里叶变换红外光谱（FTIR）、透射电子显微镜（TEM）、场发射扫描电子显微镜（FESEM）和振动磁强计（VSM）表征了复合微球的化学组成、外观形貌以及磁性能。结果表明,制备的载药Fe₃O₄/壳聚糖复合微球平均粒径约为40 nm且粒径均匀,平均磁响应时间为52 s,饱和磁化强度为3.313 2 A·m²·kg^-1。采用紫外/可见（UV/Vis）分光光度计考察了复合微球的药物包封率、载药量（质量分数）,并对微球在模拟胃液、模拟肠液、生理盐水、葡萄糖溶液和二次蒸馏水中的释药行为进行跟踪。结果表明,微球的载药量可达9.9%,药物包封率为70.8%,实验条件下在模拟肠液中具有显著的缓释效果,释放10 h药物累积释放16.06%,60 h达52.18%。     

高压静电抗溶剂法制备甲氨蝶呤-聚乳酸复合微球的研究

基于超临界CO2技术制备的甲氨蝶呤纳米粒为小分子模型药物,采用高压静电抗溶剂法制备甲氨蝶呤-聚乳酸复合微球。用扫描电镜(SEM)、傅立叶红外光谱仪(FT-IR)对该载药复合微球进行表征,并研究其载药量、包封率和药物释放曲线。实验结果表明,甲氨蝶呤-聚乳酸复合微球表面光滑,粒径分布范围在10～50μm之间;FT-IR表明,在高压静电抗溶剂过程中聚乳酸化学结构无变化,有利于其作为药物载体;随着理论载药量增加(2.5%、5%和10%),包封率减少(18.0%、7.1%和2.3%);甲氨蝶呤从聚乳酸微球中释放具有长效缓释的性能,无突释效应。     

果胶@壳聚糖复合凝胶微球的制备及释药性能EI

文中以天然多糖果胶和壳聚糖为原料,采用乳化交联的方法制备了果胶酸锌微球,再通过自组装壳聚糖层并用柠檬酸钠固化,得到了核壳结构的凝胶微球,将药物奥沙拉嗪封装在凝胶微球中,考察了其药物缓释性能。通过红外光谱、扫描电镜、能谱分析和荧光显微镜对微球形貌和核壳结构进行了表征。通过单因素变量法对凝胶微球的制备进行了优化,并对微球的药物负载性能及在模拟结肠环境中的释药行为进行了研究。结果表明,果胶@壳聚糖载药微球的最高载药量和包封率分别为29.4%和37.3%,果胶@壳聚糖复合载药微球在pH=7.4的模拟结肠液中,前12 h内的释放量仅为35.29%,72 h后奥沙拉嗪的释放量达到了89.90%,而纯果胶载药微球前12 h的释放量就已经高达78.65%,体现了壳聚糖包封层在药物缓释中的重要性。锌离子在果胶@壳聚糖复合微球和果胶微球中的释放趋势与奥沙拉嗪一致,相比于果胶微球,果胶@壳聚糖复合微球具备良好的缓释性能,可用于治疗结肠炎症疾病。     

果胶@壳聚糖复合凝胶微球的制备及释药性能EI北大核心CSCD

文中以天然多糖果胶和壳聚糖为原料,采用乳化交联的方法制备了果胶酸锌微球,再通过自组装壳聚糖层并用柠檬酸钠固化,得到了核壳结构的凝胶微球,将药物奥沙拉嗪封装在凝胶微球中,考察了其药物缓释性能。通过红外光谱、扫描电镜、能谱分析和荧光显微镜对微球形貌和核壳结构进行了表征。通过单因素变量法对凝胶微球的制备进行了优化,并对微球的药物负载性能及在模拟结肠环境中的释药行为进行了研究。结果表明,果胶@壳聚糖载药微球的最高载药量和包封率分别为29.4%和37.3%,果胶@壳聚糖复合载药微球在pH=7.4的模拟结肠液中,前12 h内的释放量仅为35.29%,72 h后奥沙拉嗪的释放量达到了89.90%,而纯果胶载药微球前12 h的释放量就已经高达78.65%,体现了壳聚糖包封层在药物缓释中的重要性。锌离子在果胶@壳聚糖复合微球和果胶微球中的释放趋势与奥沙拉嗪一致,相比于果胶微球,果胶@壳聚糖复合微球具备良好的缓释性能,可用于治疗结肠炎症疾病。     

载银壳聚糖微球的制备及其抗菌性研究

采用乳化交联法制备出载银壳聚糖微球,考察了壳聚糖相对分子质量、乳化剂用量、油水比和硝酸银浓度对微球形貌和载银量、包封率的影响,并通过抑菌圈实验对其抗菌性能进行了评价。结果表明:较低相对分子质量的壳聚糖有利于微球制备,而且所得的粒径较小,其粒径介于1～3μm,载银量可高至256 mg/g,银的包封率可达66.8%。抗菌试验结果表明,无银壳聚糖微球对大肠杆菌和金黄色葡萄球菌有一定的抑菌性,加载银后的微球则具有极为显著的抗菌效果。     

纳米羟基磷灰石/聚氨酯载药微球的制备及性能

通过乳液聚合法制备了负载阿莫西林的纳米羟基磷灰石/聚氨酯(n-HA/PU)载药微球,通过正交设计实验对其制备工艺进行了优化,采用红外光谱、热重分析、扫描电镜等分析了微球的结构和性能,对其体外药物缓释过程进行探讨。研究结果表明,复合微球粒径大小与固含量、聚乙烯吡咯烷酮(PVP)含量、搅拌速度等有关,所制备的微球平均粒径为0.8~1.2mm;载药微球的优化制备工艺条件为:原料配比-NCO∶-OH=2∶1,预聚时间180min,预聚温度80℃,nHA含量3%,固含量7%,搅拌速度600r/min,PVP用量3%,所制备微球的载药量为6.58%,包封率为86.86%。体外缓释结果表明,载药微球的释药行为符合Higuchi动力学,半衰期(t1/2)为22.29h,具有良好的药物缓释作用。     

Formulation and in vitro characterization of long-acting PLGA injectable microspheres encapsulating a peptide analog of LHRH

The present study aimed to formulate triptorelin acetate(TA)into poly(D,L-lactic-co-glycolic)acid(PLGA)based injectable sustained-release microspheres(TA-PLGA-MS)by usingdouble emulsion solvent extraction/evaporation(DESE)technique and investigate the effects of various material attributes and process parameters on the quality attributes such as size,shape,surface morphology,encapsulation efficiency(EE)and in vitro release behavior of these microspheres.Variable compositions of the outer water phase,type of the organic solvents,volume ratios of inner water phase to oil phase,PLGA concentrations,and the powers for emulsification in the preparation of the microspheres showed an influence on their quality attributes.An optimal formulation(F-2)obtained from this univariate approach possess an excellent EE value of 63.5%±3.4%and an average volumetric particle size of 35.3±1.8μm.This formulation was further accomplished with different solidification rates assisted by variable incubation temperatures,which exhibited an impact on the shape/surface and inner morphology of the microspheres.The resultant microspheres also displayed different in vitro release patterns.The matrices processed with a high incubation temperature conferred the fastest and the most complete drug release profile over the period of 63 days.Thus,the solidification rate could be identified as one of the critical process parameters that affected the quality of the PLGA based injectable microspheres specifically designed for the prolonged delivery of TA.     

预交联法制备海藻酸钠复合微球及其缓释性能

采用预交联法制备海藻酸钠(SA)/凹土(ATP)复合微球(PCM)以克服常规制备方法导致微球交联不均匀的缺陷,从而改善微球的缓释性能。将ATP先与Ca~(2+)进行部分离子交换制备Ca~(2+)-ATP,然后在与SA复合过程中同时进行预交联形成交联密度有所提高的微球内核,再采用滴注法制备该复合微球。利用红外光谱、扫描电镜和电子照片对微球结构和形貌进行表征,考察了Ca~(2+)浓度对PCM力学强度、溶胀率、载药和缓释性能的影响。结果表明,PCM在1h的累计释放率由预交联前的68%降为50%,显著改善了微球的"突释"。释放动力学研究表明,微球的释药可用Ritger-Peppas方程很好地拟合,释药速率受骨架溶蚀和药物扩散双重控制。     

Development of novel interpenetrating network gellan gum-poly(vinyl alcohol) hydrogel microspheres for the controlled release of carvedilol

Novel interpenetrating polymeric network microspheres of gellan gum and poly(vinyl alcohol) were prepared by the emulsion cross-linking method. Carvedilol, an antihypertensive drug, was successfully loaded into these microspheres prepared by changing the experimental variables such as ratio of gellan gum:poly(vinyl alcohol) and extent of cross-linking in order to optimize the process variables on drug encapsulation efficiency, release rates, size, and morphology of the microspheres. Formation of interpenetrating network and the chemical stability of carvedilol after preparing the microspheres was confirmed by Fourier transform infrared spectroscopy. Differential scanning calorimetry and x-ray diffraction studies were made on the drug-loaded microspheres to investigate the crystalline nature of the drug after encapsulation. Results indicated a crystalline dispersion of carvedilol in the polymer matrix. Scanning electron microscopy confirmed the spherical nature and smooth surface morphology of the microspheres produced. Mean particle size of the microspheres as measured by laser light scattering technique ranged between 230 and 346 µm. Carvedilol was successfully encapsulated up to 87% in the polymeric matrices. In vitro release studies were performed in the simulated gastric fluid or simulated intestinal fluid. The release of carvedilol was continued up to 12 h. Dynamic swelling studies were performed in the simulated gastric fluid or simulated intestinal fluid, and diffusion coefficients were calculated by considering the spherical geometry of the matrices. The release data were fitted to an empirical relation to estimate the transport parameters. The mechanical properties of interpenetrating polymeric networks prepared were investigated. Network parameters such as molar mass between cross-links and cross-linking density for interpenetrating polymeric networks were calculated.     

Development of Novel Interpenetrating Network Gellan Gum-Poly(vinyl alcohol) Hydrogel Microspheres for the Controlled Release of Carvedilol

Novel interpenetrating polymeric network microspheres of gellan gum and poly(vinyl alcohol) were prepared by the emulsion cross-linking method. Carvedilol, an antihypertensive drug, was successfully loaded into these microspheres prepared by changing the experimental variables such as ratio of gellan gum:poly(vinyl alcohol) and extent of cross-linking in order to optimize the process variables on drug encapsulation efficiency, release rates, size, and morphology of the microspheres. Formation of interpenetrating network and the chemical stability of carvedilol after preparing the microspheres was confirmed by Fourier transform infrared spectroscopy. Differential scanning calorimetry and x-ray diffraction studies were made on the drug-loaded microspheres to investigate the crystalline nature of the drug after encapsulation. Results indicated a crystalline dispersion of carvedilol in the polymer matrix. Scanning electron microscopy confirmed the spherical nature and smooth surface morphology of the microspheres produced. Mean particle size of the microspheres as measured by laser light scattering technique ranged between 230 and 346 µm. Carvedilol was successfully encapsulated up to 87% in the polymeric matrices. In vitro release studies were performed in the simulated gastric fluid or simulated intestinal fluid. The release of carvedilol was continued up to 12 h. Dynamic swelling studies were performed in the simulated gastric fluid or simulated intestinal fluid, and diffusion coefficients were calculated by considering the spherical geometry of the matrices. The release data were fitted to an empirical relation to estimate the transport parameters. The mechanical properties of interpenetrating polymeric networks prepared were investigated. Network parameters such as molar mass between cross-links and cross-linking density for interpenetrating polymeric networks were calculated.     

静电纺串珠纤维形貌结构及载药性能的研究进展

药物突释现象是阻碍静电纺载药纳米纤维发展的瓶颈,静电纺串珠结构纳米纤维可以通过珠粒有效担载药物,为解决药物的存储和控释问题提供了新思路。然而,串珠纤维的结构影响因素复杂,制备过程不稳定,因此,对串珠纤维形貌结构的调控及药物担载性能的研究越来越受到关注。对比了静电纺串珠纤维的各种不同形态,指出能够实现载药功能的串珠纤维应具备的形态特征,探讨了静电纺串珠纤维的成形机制,系统地分析了溶液性质和纺丝工艺参数对串珠纤维形貌结构的影响,并介绍了串珠纤维对药物的存储、释放性能。     

Encapsulation and characterization of controlled release flurbiprofen loaded microspheres using beeswax as an encapsulating agent

The aim of the present study was to extend the use of flurbiprofen in clinical settings by avoiding its harmful gastric effects. For this purpose, we designed the controlled release solid lipid flurbiprofen microspheres (SLFM) by emulsion congealing technique. Drug was entrapped into gastro resistant biodegradable beeswax microspheres which were prepared at different drug/beeswax ratios 1:1, 1:2 and 1:3 using gelatin and tween 20 as emulsifying agents. The effect of emulsifiers and the effect drug/beeswax ratios were studied on hydration rate, encapsulating efficiency, micromeritic properties, scanning electron microscopy (SEM), fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (X-RD) analysis and in vitro drug release at pH 1.2 for 2 h and at pH 6.8 for 10 h. SEM revealed that microspheres made with tween 20 were smooth while microspheres made with gelatin showed porous morphology, however, they were all spherical in nature. The practical yield (recovery) showed a dependence on drug-beeswax ratio and it was variable from 53 to 84%. High loading encapsulating efficiency of flurbiprofen from 8 to 94% was achieved. FTIR and DSC analysis confirmed the absence of any drug polymer interaction indicating drug stability during microencapsulation. X-RD of pure flurbiprofen shows sharp peaks, which decreases on encapsulation, indicating decrease in the crystallinity of drug in microspheres. The micromeritic studies confirmed the presence of excellent and good flow properties of microspheres. Entrapment efficiency, morphology, practical yield, hydration rate, flow properties demonstrated their dependence on the HLB value of emulsifiers and emulsifiers with higher HLB were found more appropriate for effective microencapsulation of flurbiprofen. The release kinetics followed zero order mechanism of drug release at pH 6.8. Release pattern depends on the morphology of flurbiprofen microspheres and amount of beeswax used in the microspheres preparation. The microspheres prepared with high HLB values i.e., tween 20 showed effective control of drug release from microspheres. The absence of drug release at pH 1.2 proved the suitability of beeswax for its use as a gastro resistant material.     

D-Optimal Designing and Optimization of Long Acting Microsphere-Based Injectable Formulation of Aripiprazole

This work was aimed to design and optimize a long acting microsphere-based injectable formulation of aripiprazole by using D-optimal experimental design methodology. Microspheres were prepared by solvent evaporation method using PLGA and cholesterol as release rate retardant materials. The microspheres were characterized for their encapsulation efficiency, particle size, surface morphology, residual solvent content, and drug release behavior. Contour plots were plotted to study the encapsulation and release behaviour of the drug from the microspheres. Desirability technique was used for the optimization of microsphere formulation composition. By using an optimum blend of drug and cholesterol in the microsphere formulation it was possible to attain a consistent drug release for a period of 14 days. The results have confirmed that the D-optimal experimental design technique can be successfully employed for designing the long acting microsphere dosage form.     

D-optimal designing and optimization of long acting microsphere-based injectable formulation of aripiprazole

This work was aimed to design and optimize a long acting microsphere-based injectable formulation of aripiprazole by using D-optimal experimental design methodology. Microspheres were prepared by solvent evaporation method using PLGA and cholesterol as release rate retardant materials. The microspheres were characterized for their encapsulation efficiency, particle size, surface morphology, residual solvent content, and drug release behavior. Contour plots were plotted to study the encapsulation and release behaviour of the drug from the microspheres. Desirability technique was used for the optimization of microsphere formulation composition. By using an optimum blend of drug and cholesterol in the microsphere formulation it was possible to attain a consistent drug release for a period of 14 days. The results have confirmed that the D-optimal experimental design technique can be successfully employed for designing the long acting microsphere dosage form.