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。     

In vitro and in vivo evaluation of targeting efficiency of Adriamycin hydrochloride magnetic microspheres

The objective of this study was to prepare magnetic microspheres as a targeting drug delivery system and to specifically evaluate its targeting efficiency. The magnetic microspheres were prepared by emulsion cross-linking techniques. Targeting efficiency was specifically investigated by experiments of biodistribution on rats and histological study. Adriamycin hydrochloride (ADR)-loaded magnetic microspheres were successfully prepared with the mean diameter of 3.853 μm (± 1.484 μm), and had its speciality of superparamagnetism. The results of the targeting efficiency study showed that application of the external magnetic field significantly increased the ADR concentration from 40.28 μg/ml to 100.70 μg/ml at 10?min, 36.99 μg/ml to 91.16 μg/ml at 60?min, and 13.71 μg/ml to 28.30 μg/ml at 180?min in liver as the targeting tissue. The relative uptake efficiencies in liver by injection treatment of ADR magnetic microspheres with external magnetic field were 3.87, 5.59, and 3.34 at 10?min, 60?min, and 180?min after administration, respectively. In conclusion, distinguished targeting efficiency was displayed, which indicated that the magnetic microspheres could be applied as a novel targeting drug delivery system.     

替莫唑胺壳聚糖缓释微球的制备及体外释药特性

目的:制备替莫唑胺壳聚糖缓释微球,并对其体外释药模式进行研究.方法:以替莫唑胺为模型药物,采用乳化交联法制备壳聚糖微球,两步优化法优化处方和制备工艺.通过测定微球的粒径及其分布、载药量、包封率和体外释放速度对微球进行质量评价.结果:优化工艺制得的微球平均粒径为(3.9±1.6)μm,载药量为(7.1±0.5)%(n=3),包封率为(25.0±0.8)%(n=3),体外释药特性研究具有良好的缓释特性,在0～8 h符合Higuchi方程,Q=11.717 26.951t1/2(r=0.980),8～24 h符合一级释放曲线,lnQ=4.37 0.007 5t(r=0.983).结论:通过优化处方和制备工艺,采用乳化交联法可制备出以壳聚糖为载体、替莫唑胺为模型药物的缓释微球,其体外释药具有明显的缓释作用.     

丙氨瑞林微球制备工艺优化和体外释放研究

目的:制备包封率高、可持续释药35 d的丙氨瑞林微球.方法:以生物可降解聚合物聚乳酸-聚羟基乙酸(PLGA)为载体,采用W/O/W复乳溶剂挥发法制备缓释丙氨瑞林微球,以包封率为观察指标,用正交设计L9(34)对微球制备工艺进行优化.在pH=7.0的磷酸盐缓冲溶液中考察微球的体外释放.结果:经优化工艺制备的丙氨瑞林微球包封率为(93.2±1.6)％,90％的微球粒径分布范围为55～65 μm.在选择的释放条件下,至35 d时,药物累积释放92.3％,突释为9.7％.结论:该制备工艺简单、稳定.优化条件下制备的丙氨瑞林微球包封率高、粒径适宜、突释少.     

盐酸噻吩诺啡缓释微球的体外释放度及其体内外相关性研究

目的 建立体内外相关性良好的盐酸噻吩诺啡缓释微球的体外释放度测定方法.方法 采用直接释药法和透析释药法测定盐酸嚷吩诺啡缓释微球的体外释放度;采用高效液相色谱法测定盐酸噻吩诺啡缓释微球在大鼠注射部位的残留量,计算微球在体内的释药速度.通过相关性评价确定最佳的体外释放度测定方法.结果 透析释药法和直接释药法均可获得良好的体内外相关性.结论 直接释药法和透析释药法均可用于测定盐酸噻吩诺啡微球的体外释放度.     

鼻用氟脲嘧啶壳聚糖微球的体外释放及溶胀影响因素

目的考察壳聚糖脱乙酰度、壳聚糖浓度、固化剂用量、固化时间以及介质pH值对氟脲嘧啶壳聚糖微球的体外释放与溶胀的影响。方法乳化化学交联法制备氟脲嘧啶鼻用微球,动态透析法检测微球的体外释放特性;根据微球吸水前后质量变化测定微球的溶胀率。结果壳聚糖的脱乙酰度越高、固化剂用量越大、固化时间越长则微球的溶胀越慢,微球的体外释放越慢;壳聚糖浓度的增加则使微球的溶胀度增加,体外释放量减少;释放介质的pH值对微球的溶胀性能影响很大,在酸性条件下微球溶胀度高且释药加快。结论影响壳聚糖微球溶胀的因素顺序为介质的pH值>固化剂用量>固化时间>壳聚糖浓度≈壳聚糖脱乙酰度;影响壳聚糖微球体外释放的因素顺序为固化剂用量>壳聚糖脱乙酰度>壳聚糖浓度,而固化时间和介质的pH值对体外释放无显著性影响。     

Formulation and evaluation of chitosan microspheres of aceclofenac for colon‐targeted drug delivery

The objective of this investigation was to develop novel colon specific drug delivery. Aceclofenac, a NSAID, was successfully encapsulated into chitosan microspheres. Various formulations were prepared by varying the ratio of chitosan, span‐85 and stirring speed and the amount of glutaraldehyde. The SEM study showed that microspheres have smooth surfaces. Microspheres were characterised by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) to confirm the absence of chemical interactions between drug and polymer and to know the formation of microspheres structure. The microspheres were evaluated for particle size, encapsulation efficiency, drug loading capacity, mucoadhesion studies, stability studies, in vitro and in vivo drug release studies. Particle sizes, as measured by the laser light scattering technique, were of an average size in the range 41–80 µm. The swelling index was in the range 0.37–0.82 and the entrapment efficiency range was 51–75% for all the formulations. The optimised batch ACM₁₃ released 83.6% at 8 h and 104% at 24 h in SCF containing rat caecal content. Eudragit coated chitosan microspheres prevented the release of the aceclofenac in the physiological environment of the stomach and small intestine and released 95.9±0.34% in the colon. With regard to release kinetics, the data were best fitted with the Higuchi model and showed zero order release with non‐Fickian diffusion mechanism. The in vivo findings suggest that aceclofenac microspheres exhibit a prolonged effect of aceclofenac in rats and produce a significant anti‐inflammatory effect. The findings of the present study conclusively state that chitosan microspheres are promising for colon targeting of aceclofenac to synchronise with chronobiological symptoms of rheumatoid arthritis. Copyright © 2010 John Wiley & Sons, Ltd.     

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。     

辛伐他汀聚乳酸微球的体外加速释放研究

目的：考察聚乳酸微球体外长期释放和加速释放的相关性，建立辛伐他汀聚乳酸微球的体外加速释放方法。方法：用紫外分光光度法测定微球中辛伐他汀的含量。采用改良的摇瓶培养法分别在不同温度的介质中进行体外加速释放试验和长期释放试验。用点点相关法考察两者的相关性。结果：PLA10000和PLA20000制备的微球在37℃放置30d内的释放分别达到92．68％和84．07％，微球在44℃，48℃和50℃下的释放均明显加速，释放动力学分别符合一级释药方程及Higuchi方程。辛伐他汀聚乳酸微球在48℃条件下的加速释放与在37℃的长期释放有良好的相关性。结论：辛伐他汀聚乳酸微球具有很好的缓释能力，采用体外加速试验的方法可以快速考察辛伐他汀聚乳酸微球的体外释药行为。     

Ketoprofen-loaded Eudragit RSPO microspheres: An influence of sodium carbonate on in vitro drug release and surface topology

Eudragit RSPO microspheres containing ketoprofen as model drug, prepared by solvent evaporation technique using acetone-liquid paraffin (heavy) solvent system were examined. Depending upon polymer concentration in the internal phase, microspheres of particle mean diameter (122.8, 213.6 and 309.5 μm) were obtained. The influence of surface washing of microspheres with n-hexane, i.e. untreated microspheres (UM) on the drug content, drug release and surface topology of microspheres were compared to those of microspheres washed with sodium carbonate, i.e. treated microspheres (TM) in order to make the non-encapsulated surface drug soluble. The significant reduction in encapsulation efficiency (p < 0.001) and drug content (p < 0.001) after treatment, in combination with the small crystalline peaks observed during XRD testing and lack of melting endotherm observed in DSC testing, suggests that the washing process actually removes a significant amount of drug (p < 0.001) from the surface and encapsulated near to the surface of the microsphere polymer matrix. Scanning electron microscopy (SEM) examination revealed that the removal of surface drug did not affect the size of microspheres but the topology of treated smallest microspheres was modified. The ketoprofen release profiles were examined in phosphate buffer pH 7.4, using USPXXIII paddle type dissolution apparatus. In general both UM and TM result in biphasic release patterns, but the initial burst effect (first release phase) of TM was lower than that of UM. The second release phase did not change for the bigger size but increased for the smallest microspheres, probably owing to the modification of matrix porosity     

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。     

不同封端的PLGA/PLA-醋酸曲普瑞林微球的制备及体内外评价

目的考察微球载体材料聚乳酸-羟基乙酸共聚物(poly-lactic-co-glycolic acid,PLGA)和聚乳酸(poly(D,L-lactide acid),PLA)的不同封端基团对于包载醋酸曲普瑞林(triptorelin acetate,TA)微球的形态、粒径、包封率、体外释放行为以及体内药效学的影响。方法使用复乳化-溶剂挥发法制备包载TA的PLGA和PLA微球;用扫描电镜观察微球的形态,用激光粒度测定仪测定微球的粒径;建立高效液相色谱法(HPLC)用于TA包封率及体外释放度的测定;采用酶联-免疫吸附法考察了微球经肌肉注射后对正常雄性Sprague Dawley大鼠血浆睾酮浓度的影响。结果制备得到的微球形态为球形或类球形,平均粒径约为30μm。PLGA和PLA,尤其是PLGA,其分子末端基团对TA的包封率和体外释放速率均有影响。酯封端的PLGA微球的包封率显著高于酸封端的微球,而酯封端的释放速度要慢于酸封端。体内药效学实验结果显示,大鼠体内睾酮水平在注射微球后两个小时达到峰值,之后逐渐下降,不同微球之间无显著性差异。结论不同封端结尾的PLGA和PLA对微球形态、包封率和体外释药速率有显著影响,但对正常大鼠体内睾酮水平的影响没有显著性差异。     

醋酸戈舍瑞林缓释微球的制备及体外释药研究

目的制备醋酸戈舍瑞林缓释微球,考察其一般性质和体外释药特性。方法采用复乳-液中干燥法制备醋酸戈舍瑞林微球,测定微球的外观形态、粒度分布和体外释药曲线。结果微球形态规则,粒径约为85.6μm,微球体外释药规律符合Higuchi方程：Q=16.202t1/2＋1.550 3,r=0.991 0。结论制备的醋酸戈舍瑞林微球具有长时间的缓释作用。     

利培酮微球在家兔体内外的释药行为

目的制备生物可降解的利培酮微球,并考察其在家兔体内外的释放。方法以聚乳酸羟基乙酸为基质,乳化-溶剂挥发法制备利培酮微球,并进行长期及加速体外释放和家兔体内释放研究。结果体外释药可采用溶蚀-扩散模型拟合,微球体内释药平稳,体内外释放相关性好。结论利培酮在体内外具有缓释效果,可采用加速释放实验来模拟体内外释放。     

胸腺肽明胶微球的制备和体外释药的特性

目的:为提高胸腺肽的生物利用度,增强疗效,制备胸腺肽的明胶微球.方法:用乳化交联法制备胸腺肽明胶微球,正交设计法筛选其最佳制备工艺,Lowry法测定药物的含量,计算微球的载药量、包封率及体外释药量.结果:微球粒径范围为1.0～30.2 μm,平均粒径为14.64 μm,平均载药量为20.20%(w/w),平均包封率为80.82%,其体外释药符合Higuchi方程,稳定性考察实验结果表明其稳定性较好.结论:本法制备的胸腺肽明胶微球粒径分布集中,粒径大小符合设计要求,体外释药有明显的缓释作用,具有良好应用前景.     

In vitro and in vivo evaluation of ranitidine hydrochloride loaded hollow microspheres in rabbits

The objective of this investigation was to develop the hollow microspheres as a new dosage form of floating drug delivery systems with prolonged stomach retention time. Hollow microspheres containing ranitidine hydrochloride (RH) were prepared by a novel solvent diffusion-evaporation method using ethyl cellulose (EC) dissolved in a mixture of ethanol and ether (6:1.0, v/v). The yield and drug loading amount of hollow microspheres were 83.21±0.28% and 20.71±0.32%, respectively. The in vitro release profiles showed that the drug release rate decreased with increasing viscosity of EC and the diameter of hollow microspheres, while increased with the increase of RH/EC weight ratio. Hollow microspheres could prolong drug release time (approximately 24 h) and float over the simulate gastric fluid for more than 24 h. Pharmacokinetic analysis showed that the bioavailability from RH-hollow microspheres alone was about 3.0-times that of common RH gelatin capsules, and it was about 2.8-times that of the solid microspheres. These results demonstrated that RH hollow microspheres were capable of sustained delivery of the drug for longer period with increased bioavailability.     

胰岛素壳聚糖胶态纳米粒的制备及体外释药性能

采用离子趋向凝胶化法制备了胰岛素壳聚糖胶态微粒,并考察了外观、粒径和体外释药性能.所得产品呈球形,表面光滑圆整,平均粒径为276nm,多分散系数为0.08.体外释药呈pH依赖性,释药速度受载药量及泊洛沙姆188含量的影响.     

处方和工艺参数对盐酸昂丹司琼微球体外释放度的影响

目的：考察处方工艺参数对微球体外释放度的影响.方法：采用O/O型乳化溶剂挥发法,以乳酸-羟基乙酸共聚物为载体,制备盐酸昂丹司琼（Ondansetron hydrochloride,OND）微球.采用紫外分光光度法测定微球的体外释放度.结果：选择对OND具有较好溶解能力的混合溶剂为内油相溶剂,可以降低突释;增加理论载药量,延缓正己烷加入的时间和减小粒径可以增加OND微球的释药速度.结论：通过对处方和工艺的调节可使OND微球的体外释药曲线符合Higuchi方程,2周的累积释放量在80%左右.     

In vitro dissolution of pH sensitive microparticles for colon-specific drug delivery

Objective: The objective of this work is to prepare oral dosage systems based on enteric materials in order to verify their possible use as Colon-Specific Drug Delivery Systems (CSDDSs).

Methodology: In particular, three different copolymers of methyl-methacrylate (MMA) - acrylic acid (AA) are synthesized with increasing percentage of MMA (from 70% to 73%) and they are used to produce microparticles by the double-emulsion solvent evaporation method. The microparticles, loaded using theophylline as model drug, are then tested for drug release under varying pH to reproduce what happens in the human GI tract.

Results: All the investigated systems have shown an effective pH sensitiveness: they show a good gastro-resistance, releasing the model drug only at higher pH, small intestine or colon, depending on the kind of used copolymer.

Conclusion: The results confirm the usefulness of both the materials and the methods proposed in this study for colon-specific delivery applications.     

双氯芬酸钠壳聚糖明胶复合微球的释药机制研究

目的制备双氯芬酸钠壳聚糖明胶复合微球(DS-CGMs),探讨其体外释药机制。方法建立DS-CGMs体外释放度的测定方法;研究药物从微球中释放的影响因素;分别考查双氯芬酸钠明胶微球(DS-GMs)、双氯芬酸钠壳聚糖微球(DS-CMs)及DS-CGMs的体外释药情况,并通过数学原理和相关模型探讨其释放行为和机制。结果DS-GMs、DS-CMs以扩散和骨架溶蚀作用释放,而DS-CGMs呈骨架溶蚀作用机制,具有更好的缓释效果。结论获得较为满意的DS-CGMs,其体外释药具有一定的缓释性。