顺铂缓释多囊脂质体的制备和体外释放性能研究

目的 制备包封率高和缓释作用好的顺铂缓释多囊脂质体,并与反相蒸发法制备的顺铂普通脂质体比较其体外释药性能。方法 用复乳法制备顺铂多囊脂质体,非火焰原子吸收分光光度法测定顺铂含量,磷脂酶试剂法测定脂质体中磷脂的浓度。测定包封率和体外释药性。结果顺铂多囊脂质体平均粒径为16.6 μm,跨距为1.0。顺铂包封率可高达80%以上。顺铂缓释多囊脂质体的体外释药符合一级释药规律, 释药t_1/2为37.7 h,比反相蒸发法制备的顺铂普通脂质体延长8.4倍。经差示热分析发现辅助膜稳定剂有明显的膜稳定作用。结论顺铂多囊脂质体包封率高,并具有良好的缓释作用。     

Multivesicular liposomes for sustained release of bevacizumab in treating laser-induced choroidal neovascularization

Bevacizumab is an anti-vascular endothelial growth factor drug that can be used to treat choroidal neovascularization (CNV). Bevacizumab-loaded multivesicular liposomes (Bev-MVLs) have been designed and developed to increase the intravitreal retention time of bevacizumab and reduce the number of injection times. In this study, Bev-MVLs with high encapsulation efficiency were prepared by double emulsification technique, and antibody activity was determined. The results revealed that 10% of human serum albumin (HSA) could preserve the activity of bevacizumab. In vitro release of Bev-MVLs appeared to be in a more sustained manner, the underlying mechanisms of Bev-MVLs indicated that bevacizumab was released from MVLs through diffusion and erosion. Results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that bevacizumab could retain its structural integrity after being released from MVLs in vitro. In vivo imaging was used to evaluate the retention time of antibody in rat eyes, while pharmacokinetic analysis was performed on rabbit eyes. These results indicated that Bev-MVLs exhibited sustained release effects as compared to bevacizumab solution (Bev-S). Bev-MVLs could effectively inhibit the thickness of CNV lesion as compared to Bev-S at 28?days after treatment. Furthermore, these data suggest that Bev-MVLs are biologically feasible to increase the retention time of bevacizumab in vitreous humor. This novel Bev-MVLs may therefore serve as a promising sustained release drug delivery system for the treatment of CNV.     

Multivesicular liposome formulations for the sustained delivery of ropivacaine hydrochloride: Preparation,characterization, and pharmacokinetics

The aim of the present study was to design a depot delivery system of ropivacaine hydrochloride using multivesicular liposomes (RP-MVLs) to overcome the limitations of conventional therapies and to investigate it’s in vivo effectiveness for sustained delivery. RP-MVLs were prepared by the multiple emulsion method. Appearance, particle size, encapsulation efficiency, zeta potential, and initial stability of RP-MVL were also studied. The in vitro release of RP-MVLs formulations was found to be in a sustained manner. Three batches of RP-MVLs were prepared and the release profile in vitro fitted to a first-order equation. RP-MVLs releasing mechanism was also studied and it was indicated that the drug released from MVLs by diffusion and erosion. Following subcutaneous administration to rats, the time to reach maximum (T_max) of RP-MVLs formulations was significantly (p?<?0.01) later than that of RH solution. The concentrations of RP-MVLs have steadily changed in the low level, which significantly (p?<?0.01) lower than RH solution. T_1/2 and MRT were significantly prolonged (p?<?0.01). Besides, AUC was also increased significantly (p?<?0.01). The increase in AUC and decrease in C_max reflects that the MVL formulations could reduce the toxic complications and limitations of conventional injected formation therapies.     

盐酸纳曲酮多囊脂质体的处方及制备工艺研究

目的：制备盐酸纳曲酮多囊脂质体（DepoNTX）,并考察其理化性质。方法：采用复乳法制备DepoNTX;RP-HPLC法测定含量、包封率;以包封率为指标,单因素及正交试验筛选、优化工艺和处方;光学显微镜下观察多囊脂质体形态、用库尔特计数仪测定其粒径和粒度分布。结果：制备的最佳条件是卵磷脂/胆固醇为1：1（摩尔比）,形成复乳的振荡时间为10s,L-赖氨酸的浓度为40mmol·L-1,初乳和第二水相的体积比为1：2.5。粒径范围为5～50μm,平均粒径为12.4μm,包封率为44.5%。结论：制备的DepoNTX包封率较高,粒子表面呈光滑球形,内部具有非同心的多囊泡结构。     

酪丝亮肽多囊脂质体的制备和体外释放研究

目的:制备酪丝亮肽多囊脂质体,并考察其体外释药性能。方法:采用复乳法制备酪丝亮肽多囊脂质体,RP-HPLC法测定酪丝亮肽含量,以稳定性、包封率和体外释放为指标,正交试验设计法对酪丝亮肽多囊脂质体处方工艺进行优化。结果:酪丝亮肽多囊脂质体粒径均一,有80%的粒径分布在20~30μm,包封率达92.43%。酪丝亮肽多囊脂质体体外释放符合Korsmeyer-Peppas模型,37℃条件下在PBS介质中释药t1/2达111.5 h。结论:酪丝亮肽多囊脂质体稳定性好,包封率高,具有良好的缓释效果。     

Preparation and characterization of chitosan microparticles for oral sustained delivery of gliclazide: in vitro/in vivo evaluation

Chitosan microparticles were prepared with tripolyphosphate (TPP) by ionic cross‐linking with gliclazide (GLZ) as a model drug. The particle sizes of TPP‐chitosan microparticles ranged from 675–887 µm with loading efficiencies of greater than 94%. Chitosan concentration, TPP solution pH, and glutaraldehyde volume solution added to the TPP cross‐linking solution affected drug release characteristics. Pectin interactions with cationic chitosan on the surface of TPP/chitosan microparticles led to the formation of polyelectrolyte complex films that improved drug sustained release performance. In vivo testing of the GLZ‐chitosan microparticles in diabetic albino rabbits demonstrated a significant antidiabetic effect of GLZ/chitosan microparticles after 8 h that lasts for 18 h compared with GLZ powder that produced a maximal hypoglycemic effect at 4 h, suggesting that GLZ/chitosan microparticles represent an improved system for the long‐term delivery of GLZ. Drug Dev Res 72: 235–246, 2011. © 2010 Wiley‐Liss, Inc.     

溴新斯的明多囊脂质体的制备及其体外释放行为的初步研究

目的:制备溴新斯的明多囊脂质体(NB-MVL),并对其体外药物释放行为进行考察。方法:采用复乳法制备载药多囊脂质体,并用单因素试验优化处方,以动态透析技术与ƒ₂相似因子评价法对NB-MVL与溴新斯的明在体外不同释放介质中的释放行为进行研究,计算其药物释放度与相似因子。结果:NB-MVL的包封率受投料比、药物浓度等因素影响;NB-MVL在不同的释放介质中所获得的释放模型均符合Weibull模型,同时与溴新斯的明溶液在不同释放介质中所得累积释放曲线间的相似因子小于50。结论:本试验制备所得NB-MVL包封率较高,且体外药物释放行为与溴新斯的明存在显著性差异,表现出良好的缓释作用。     

Multivesicular liposome (MVL) sustained delivery of a novel synthetic cationic GnRH antagonist for prostate cancer treatment

Objectives Multivesicular liposomes (MVLs) are often used as an appropriate carrier for delivering peptides due to high drug loading, relative stability and extended‐release behaviour. However, when cationic amphipathic peptides are involved, some challenges may be encountered, including instability of multiple emulsions due to interaction between peptides and lipid membranes (electrostatic and hydrophobic interaction). LXT‐101, a cationic amphipathic peptide, is a novel antagonist of gonadotropin‐releasing hormone (GnRH) for prostate cancer treatment. The purpose of the current research was to explore simple methods of determining the interaction between peptide and lipid bilayer and to prepare MVLs of LXT‐101 (DepoLXT‐101) by the modified DepoFoam technique. Methods The anionic surfactants were added in the process of DepoLXT‐101 preparation in order to minimize the effect of instability resulting from cationic peptides. Key findings DepoLXT‐101 was obtained with good efficiency and reproduction. The integrity of encapsulated peptide was maintained as shown by RP‐HPLC. DepoLXT‐101 particles were characterized by morphology and particle size distribution and in‐vitro release was also investigated. The release behaviour in vitro in medium of sodium chloride at 37°C showed that 70–90% of LXT‐101 was released slowly from MVLparticles over 11 days. According to the fitting results of Ritgar‐Pepps model, the in‐vitro release of DepoLXT‐101 was mainly governed by Fick's diffusion. Conclusions The data obtained from in‐vivo study indicated that a sustained anticancer effect can be achieved over a 7‐day period with subcutaneous administration of DepoLXT‐101 in rats.     

阿糖胞苷多囊脂质体的制备及体外释放度考察

目的制备阿糖胞苷多囊脂质体,并考察其体外释放特性。方法采用复乳法制备阿糖胞苷多囊脂质体;RP-HPLC法测定含量、包封率和体外释放特性;以包封率为指标,单因素及正交试验筛选、优化工艺和处方;光学显微镜下观察多囊脂质体形态;以激光粒度测定仪测定粒径。结果一次乳化时间为8 min、氮气流速为0.3 m3.h-1时包封率最高;优化处方中二油酰磷脂酰胆碱(DOPC)、二棕榈酰磷脂酰甘油(DPPG)、胆固醇(CH)、三油酸甘油酯(TO)的质量浓度分别为10、2、7.5、4 g.L-1,赖氨酸浓度为40 mmol.L-1,有机溶剂选择氯仿-乙醚(体积比1∶1)。阿糖胞苷多囊脂质体在400倍显微镜下形态光滑、圆整,内部呈蜂窝状,无磷酯碎片;平均粒径19.49μm,跨距0.91;包封率达70%以上;以人空白血浆为释放介质,两周释放药物约60%。结论制备的阿糖胞苷多囊脂质体外观良好,包封率较高,体外释放试验表明药物缓慢释放,无突释现象。     

盐酸利多卡因多囊脂质体的制备和质量评价

目的:制备具有缓释特性的盐酸利多卡因多囊脂质体,考察其理化性质。方法:以卵磷脂和胆固醇为膜材,采用复乳法制备盐酸利多卡因多囊脂质体,用透射电镜观察其外观形态,用激光粒度分析仪测定粒径,检测包封率和体外释药特性。结果:盐酸利多卡因多囊脂质体的外观形态圆整、规则,粒径分布在300～700nm及1～6μm两区域,包封率为(27.10±0.66)%。多囊脂质体在pH 7.4的磷酸盐缓冲液中,24h的累积释药百分率为(92.7±3.6)%。结论:盐酸利多卡因多囊脂质体具有一定的缓释特性。     

盐酸曲美他嗪缓释片的研制及其体外释药特性考察

目的:研制盐酸曲美他嗪(TMZ)缓释片,并考察其体外药物释放特性。方法:以羟丙基甲基纤维素(HPMC)为主要骨架材料,采用湿法制粒压片法,制备TMZ缓释片;以释放度为评价指标,采用正交试验设计对处方进行优化;根据药物不同时间释放度,拟合释放度方程,确定释药特性。结果:TMZ缓释片的处方组成为:HPMC 90 mg,羧甲基纤维素钠30 mg,微晶纤维素60 mg,10%聚乙烯吡咯烷酮-乙醇溶液(w/v)适量,硬脂酸镁2 mg;12 h释放度为(98.1±1.8)%,体外释放曲线符合一级动力学方程(r=0.994 2);压片力对药物释放有一定影响。结论:研制的TMZ缓释片制备工艺简单,重现性好,释药特性达到缓释要求。     

盐酸万乃洛韦缓释片的释放度

目的:建立盐酸万乃洛韦缓释片体外释放度测定的质量标准.方法:以水为释放介质,检测波长为251 nm,对其进行常规的方法学进行研究.结果:本法的平均回收率分别为99.8%,99.9%,100.0%,RSD分别为0.96%,0.41%,0.59%,在2.7～19.5 mg*L-1浓度范围内,浓度与吸收度有良好的线性关系,r=0.9999(n=7).本品释放度受转速影响较小,而不同方法及介质pH值影响较大,同批产品的释放度均一性较好.结论:本法适用于该制剂的质量控制.     

4种盐酸二甲双胍缓释片在Beagle犬体内生物等效性比较

目的比较4种盐酸二甲双胍缓释片在Beagle犬体内的生物等效性。方法采用单剂量随机四周期四交叉试验设计。8只Beagle犬分别灌胃给予4种盐酸二甲双胍缓释片（受试制剂A、B、D,参比制剂C）50mg·kg^-1。于给药前及给药后不同时间点取血,采用HPLC法测定血浆中盐酸二甲双胍浓度,计算主要药动学参数,并评价各受试制剂的相对生物利用度和生物等效性。结果受试制剂D、A、B和参比制剂C的主要药动学参数为：tmax（2．6±1．2）、（2．1±0．9）、（2．1±0．6）和（2．7±0．5）h,ρmax（8881．7±2575．1）、（9587．5±2072．0）、（8189．3±2013．8）和（8579．3±1691．9）μg·L^-1,t1/2（4．4±0．6）、（4．6±0．4）、（4．7±1．3）和（4．2±1．0）h,AUC0→t（61378．8±18731．0）、（56602．8±10737．8）、（46766．1±9515．0）和（56754．2±12384．2）μg·h·L^-1,AUC0→∞（62863．1±19047．8）、（57975．5±11186．1）、（48185．2±9815．1）和（58372．7±13672．0）μg·h·L^-1,MRT（0．16±0．01）、（0．17±0．01）、（0．19±0．05）和（0．17±0．02）h。受试制剂D、A、B的相对生物利用度分别为（118．0±61．4）％、（107．0±42．0）％和（91．4±12．2）％。结论3种受试制剂和参比制剂C生物等效,其中受试制剂D的生物利用度最高,其次是A、B。     

纳曲酮微球缓释制剂在犬体内的药代动力学(英文)

目的　评价一种可注射的纳曲酮微球缓释制剂在 4条犬体内的药物释放过程 ,生物相容性和生物降解性情况。方法　用高效液相色谱 电化学检测器法 ,以纳洛酮为内标来研究纳曲酮的药代动力学数据和注射局部残留微球中的纳曲酮含量 ,在肉眼和显微镜两个水平进行注射局部的组织病理学检查。结果　犬im 0 .5或 1 .0mg·kg-1盐酸纳曲酮的药代动力学研究得出其血浆清除率为 0 .66～ 0 .73L·min-1,t1/2 β为 60 .0～ 67.2min,经过 1周的无药物处理的清除期 ,进入 4周的纳曲酮微球注射期。每只犬注射了 1g微球〔纳曲酮 ( 2 3 .6± 1 .5 )mg·kg-1〕后 ,纳曲酮的血药浓度超过 1 μg·L-1达 2 6～ 2 8d ,单位剂量 (mg·kg-1)的cmax约为盐酸纳曲酮的 1 %。在4条犬体内 ,为( 93 .0± 4.1 ) %的剂量被吸收。除了轻微的炎症外 ,未发现严重的副作用。结论　通过本实验的初步研究表明该纳曲酮微球缓释制剂安全、稳定 ,完全地缓慢释放约 1个月。     

Ivermectin-loaded microparticles for parenteral sustained release: in vitro characterization and effect of some formulation variables

Ivermectin (IVM) is a BCS II drug with potent antiparasitic activity in veterinary applications. In this study, poly(lactide-co-glycolide) (PLGA) and poly(DL-lactide) (PLA) Ivermectin-loaded microparticles were prepared by the simple emulsion (O/W) solvent evaporation method in order to obtain sustained release formulations for parenteral applications. The effects of polymer end-groups (ester or free acid) and the addition of the hydrophilic polyvinylpyrrolidone polymer (PVP) in in vitro drug release profiles were also studied. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analysis showed that IVM was present in an amorphous state or as a molecular dispersion within the polymers or theirs mixtures with PVP and that a PVP-drug complex was formed. Drug entrapment efficiency in the microparticles (>90%) was independent of the polymer composition, the end groups and the presence of PVP. However, microscopic (SEM) observations showed that the addition of PVP led to more porous microparticles accompanied by the increased rates of drug release.     

定制设计法在盐酸丁咯地尔缓释片处方设计中的应用

目的应用定制设计法优化盐酸丁咯地尔缓释片的处方。方法以片芯中乙基纤维素和氯化钠比例的变化、包衣增重为考察因素,以不同时间点的累积释放量为优化指标,应用定制设计法筛选最佳处方,并对优化处方进行验证。结果最优处方组成为,盐酸丁咯地尔600 mg、乙基纤维素90 mg、氯化钠10 mg、包衣增量为3%,12 h累积释放量为80%以上,体外释放曲线平稳。结论采用定制设计法得到了盐酸丁咯地尔缓释片的处方优化模型,应用优化处方制备缓释片所得的实测值与预测值无明显差异,实现了处方优化。     

右旋布洛芬/酸改性蒙脱土缓释干混悬剂的制备及其体内外研究

目的：研究右旋布洛芬/酸改性蒙脱土缓释干混悬剂体外释放及体内药动学特性。方法：通过沉降体积比和再分散性等检查,初步评价右旋布洛芬/酸改性蒙脱土缓释干混悬剂质量,采用体外溶出装置进行体外释放试验测定右旋布洛芬体外累积释放量;以大鼠为动物模型,测定给药后的血药浓度,采用DAS2.0程序计算药动学参数。结果：右旋布洛芬/酸改性蒙脱土干混悬剂3 h内沉降体积比大于0.9,且混悬剂再分散性好,流动性好;体外释药符合Higuchi方程（r=0.970 1）;并具有明显缓释作用;体内试验表明,受试制剂和参比制剂的主要药动学参数C_max分别为（86.05±5.96）,（123.5±41.74）μg·mL^-1;AUC_{0-24 h}分别为（644.49±73.26）,（439.88±84.41）μg·mL^-1·h,t_1/2分别为（5.58±0.55）,（2.36±0.55） h;各参数间比较具有统计学差异（P<0.05）,受试制剂的达峰时间t_max延长到2 h,t_1/2和MRT比参比制剂分别延长2.36倍和2.47倍,可见右旋布洛芬/酸改性蒙脱土干混悬剂在大鼠体内具有明显缓释作用。结论：右旋布洛芬/酸性蒙脱土干混悬剂体内外均具有良好的缓释作用。     

双嘧达莫缓释微丸的研制及其体外释放特性

目的：制备双嘧达莫pH非依赖型缓释微丸，使药物释放不受胃肠道pH值变化及个体差异的影响。方法：采用固体分散技术，将药物与联合载体（Eudragit L、EC和PEG 6000）的混和有机液喷包于微晶纤维素（MCC）空白丸芯上形成膜衣骨架型共沉淀物结构，以正交设计进行处方优化，考察不同pH条件下缓释微丸的释放特性。结果：缓释微丸的体外药物释放呈pH非依赖型释放特征，符合一级动力学方程。结论：具有溶解度pH依赖性的药物，以固体分散技术处理，通过不同性质载体的调节作用，可以制成pH非领带型的缓释制剂。     

辛伐他汀-烟酸双层缓释片的制备及其体外质量评价

目的 制备辛伐他汀(SVT) -烟酸(NA)双层缓释片并进行体外质量评价.方法 分别通过正交实验和单因素实验,筛选NA缓释层与SVT常释层处方,确定最佳处方组成并制备SVT-NA双层缓释片,测定缓释片中NA与SVT的含量.以国内已上市NA缓释片为参比制剂,测定自制双层缓释片中NA的释放度,计算释放度相似因子(f2),并进行方程拟合.按照中国药典2010版中SVT普通片溶出度测定条件,测定自制双层缓释片常释层中SVT的溶出度.结果 自制双层缓释片中NA的释放度与市售NA缓释片相似(f2＞75),其释放行为符合Higuchi方程;常释层中SVT 30 min内的累积溶出度＞98％,符合中国药典有关规定.结论 SVT-NA双层缓释片处方组成合理,制备工艺稳定,重现性良好,有望开发成为新的复方制剂.     

非洛地平缓释制剂体外释放度比较

目的:对不同厂家非洛地平缓释制剂的体外释放度进行比较。方法:按照非洛地平的部颁标准,采用桨法测定非洛地平缓释制剂的释放度,通过选用数学模型线性拟合,求出参数,进行方差分析。结果:B样品释放度的均一性和重现性均好于A样品,A样品同一样品不同批号间释放度差异极具显著性(P<0.01),B样品有2个批号间差异具显著性(P<0.05)。结论:两个厂家的产品的释放度均符合部颁标准规定,B样品释放度好于A样品。