利巴韦林注射液与3种药物的配伍稳定性

目的考察利巴韦林注射液分别与鱼腥草、硫酸庆大霉素、柴胡等药物的配伍稳定性.方法采用紫外分光光度法测定配伍后6 h内利巴韦林的含量变化,同时观察配伍液的pH值、外观及紫外吸收光谱的变化.结果利巴韦林与3种药物配伍后pH值、外观、含量及紫外光谱均无显著变化.结论利巴韦林与3种药物配伍6 h内基本稳定,临床上可配伍使用.     

利巴韦林注射液与3种药物的配伍稳定性

目的 考察利巴韦林注射液分别与鱼腥草、硫酸庆大霉素、柴胡等药物的配伍稳定性。方法 采用紫外分光光度法测定配伍后6h内利巴韦林的含量变化，同时观察配伍液的pH值、外观及紫外吸收光谱的变化。结果 利巴韦林与3种药物配伍后pH值、外观、含量及紫外光谱均无显著变化。结论 利巴韦林与3种药物配伍6h内基本稳定，临床上可配伍使用。     

利巴韦林片在人体的药物动力学和生物等效性研究

目的研究利巴韦林片在健康人体内的药物动力学,并对2种制剂的生物等效性进行判定。方法采用液质联用（LC-MS／MS）法测定血浆中利巴韦林浓度并计算其主要药动学参数。结果受试制剂和参比制剂中利巴韦林的主要药动学参数如下：tmax分别为（1．35±0．38）、（1．30±0．50）h;Cmax分别为（674．8±227．7）、（693．94±223．3）ng·mL-1,t1／2分别为（25．6±6．0）、（26．6±5．3）h;AUC0-1分别为（8606．2±2132．0）、（8452．0±1978．8）ng·h·mL-1,AUC0-∞分别为（9903．3±2494．1）、（9632．1±2404．2）ng·h·mL-1,相对生物利用度为（102．2±9．5）％。结论2种利巴韦林制剂具有生物等效性。     

利巴韦林注射液与3种药物的配伍稳定性

目的 考察利巴韦林注射液分别与鱼腥草、硫酸庆大霉素、柴胡等药物的配伍稳定性。方法 采用紫外分光光度法测 定配伍后6 h内利巴韦林的含量变化,同时观察配伍液的pH值、外观及紫外吸收光谱的变化。结果 利巴韦林与3种药物配 伍后pH值、外观、含量及紫外光谱均无显著变化。结论 利巴韦林与3种药物配伍6 h内基本稳定,临床上可配伍使用。     

利巴韦林的含量测定以及人体药代动力学的分析研究

目的测定人体血浆中利巴韦林的含量,探讨利巴韦林在人体药代动力学的研究情况。方法随即选取6例身体健康的男性志愿受试者,分成两组,早晨空腹口服利巴韦林350 mg,72 h内测定其药代动力学,研究其临床药学性质。结果 A品种的利巴韦林参数为Tmax(3.48±3.01)h,Cmax(208.76±66.56)μg/L,AUC(0⁷2 h)参数为(5108.14±1495.56)μg/L;而B品种的利巴韦林参数为Tmax(3.37±2.84)h,Cmax(215.7±61.54)μg/L,AUC(072 h)参数为(5108.14±1495.56)μg/L;而B品种的利巴韦林参数为Tmax(3.37±2.84)h,Cmax(215.7±61.54)μg/L,AUC(0⁷2 h)参数为(5086.19±1506.47)μg/L。两种利巴韦林的药代动力学参数结果表明(P>0.05),对比无显著性差异及统计学意义。结论两种利巴韦林具有同样的疗效等效性。本次研究为药剂开发工作者提供了重要数据。     

甲磺酸帕珠沙星与利巴韦林注射液在葡萄糖注射液中的配伍稳定性

目的考察注射用甲磺酸帕珠沙星与利巴韦林注射液在葡萄糖注射液中的配伍稳定性。方法采用紫外分光光度法,测定注射用甲磺酸帕珠沙星与利巴韦林注射液在5％葡萄糖中配伍后,在室温（22℃）下6h内甲磺酸帕珠沙星与利巴韦林含量变化,观察外观并测定pH值。结果两种药物配伍后,6h内外观、pH值及含量均无明显变化。结论注射用甲磺酸帕珠沙星与利巴韦林注射液在5％葡萄糖注射液中配伍后6h内可以使用。     

2种利巴韦林制剂的人体生物等效性研究

目的:研究2种利巴韦林制剂的生物等效性。方法:采用随机交叉试验设计,采用液-质联用法测定20例男性健康志愿者单剂量口服150mg利巴韦林受试泡腾片(受试制剂)及利巴韦林受试颗粒(参比制剂)后利巴韦林的血药浓度,并计算相关药动学参数。结果:利巴韦林受试制剂与参比制剂的主要药动学参数分别为:t1/2(44.00±8.75)、(44.89±10.44)h,tmax(1.0±0.7)、(0.8±0.2)h,cmax(424.12±133.03)、(406.09±108.22)ng.mL-1,AUC0～108h(4997.59±1322.31)、(4921.16±1030.61)ng.h.mL-1。以AUC0～108h计算,利巴韦林受试制剂平均相对生物利用度为(105.4±37.4)%。统计学结果表明,2种制剂主要药动学参数t1/2、cmax、tmax、AUC0～108h均无显著性差异。结论:本方法专属、灵敏、准确,利巴韦林2种制剂在人体内具有生物等效性。     

利巴韦林注射液与3种常用输液的配伍稳定性

目的研究室温6h内利巴韦林注射液与50g·L-1葡萄糖注射液、9g·L-1氯化钠注射液和复方葡萄糖氯化钠注射液的配伍稳定性,为临床用药提供科学依据。方法采用反相高效液相色谱法测定利巴韦林注射液与输液配伍后,6h内利巴韦林的含量及有关物质,同时考察配伍液的外观和pH值。结果利巴韦林与输液配伍6h后,外观、pH值、含量和有关物质均无明显变化。结论利巴韦林注射液可与50g·L-1葡萄糖注射液、9g·L-1氯化钠注射液和复方葡萄糖氯化钠注射液配伍使用。     

多效胃镜乳的处方改进及稳定性考察

目的:考察氟罗沙星葡萄糖注射液和利巴韦林的配伍稳定性。方法:在25℃的避光和室内自然光条件下,用紫外分光光度法分别测定24 h内利巴韦林和氟罗沙星葡萄糖注射液配伍前后的含量变化情况,同时记录其外观及pH值变化。结果:利巴韦林和氟罗沙星平均回收率分别为99．52％,99．31％;RSD分别为0．450％,0．364％。常温放置6 h内配伍液外观、pH值、含量均无明显变化。结论:6 h内利巴韦林与氟罗沙星葡萄糖注射液配伍基本稳定。     

头孢替唑钠与利巴韦林2种注射液的配伍试验

目的:在25℃和37℃条件下6h内观察头孢替唑钠与利巴韦林注射液的配伍液稳定性.方法:采用紫外分光光度法测定配伍液中头孢替唑钠及利巴韦林在6h内的含量变化,同时观察配伍液的外观及pH变化.结果:配伍液在25℃和37℃条件下0～6h内其外观、pH值及含量均无明显变化.结论:在上述条件下,注射用头孢替唑钠与利巴韦林注射液可配伍应用.     

葡萄糖酸依诺沙星注射液与利巴韦林注射液配伍稳定性的研究

目的研究葡萄糖酸依诺沙星注射液与利巴韦林注射液的配伍稳定性。方法考察溶液配伍前后的颜色、pH值、不溶性微粒等变化情况,并用UV和HPLC分别考察配伍前后葡萄糖酸依诺沙星和利巴韦林的含量变化。结果葡萄糖酸依诺沙星注射液与利巴韦林注射液配伍,6 h内溶液颜色基本无变化、pH值、不溶性微粒及含量无明显变化。结论两药配伍后的理化性质稳定,在6h内可以配伍使用。     

利巴韦林脂质体吸入粉雾剂的研制与初步评价

目的 为解决利巴韦林存在的明显不良反应问题,研制利巴韦林脂质体吸入粉雾剂,并初步评价其质量特性。方法 采用薄膜分散法制备利巴韦林脂质体,再冻干制备成利巴韦林脂质体粉雾剂,并考察制剂的外观形态、流动性、松密度、包封率、复溶液粒径、聚合物分散指数、电位及亲水性。结果 利巴韦林脂质体粉雾剂形态、粒径、电位、流动性与亲水性均较好,能满足粉雾剂給药的基本要求。结论 应用该方法制备利巴韦林脂质体粉雾剂的制剂技术是可行的,为后续体内外研究提供制剂学技术依据。     

Effects of sialic acid derivative on long circulation time and tumor concentration of liposomes

The effects of a sialic acid derivative, Neu5Aβ-PA, on the blood circulation and tissue distribution of liposomes composed of dipalmitoylphosphatidylcholine (DPPC), cholesterol (Chol) and Neu5Aβ-PA were investigated compared with liposomes composed of DPPC, Chol and monosialoganglioside GM₁, in mice and rats. When liposomes containing Neu5Aβ-PA were intravenously administered into mice, the plasma concentration of liposomes containing Neu5Ac/3-PA was increased, and the liver and spleen uptakes were decreased; there was no significant difference in tissue distribution between liposomes containing Neu5Aβ-PA (DPPC/Chol/Neu5Aβ-PA= 10: 10:3) and those containing GM₁, (DPPC/Chol/GM₁= 10:10:1). On the other hand, the plasma concentration of liposomes containing Neu5Aβ-PA was significantly greater than that of liposomes containing GM₁, at all times determined in rats, and was about 30.7- and 10.3-fold that of liposomes containing GM₁, at 6 and 24 h, respectively. The liver and spleen uptakes of liposomes containing Neu5Aβ-PA at 6 h were significantly reduced compared with those of liposomes containing GM, in rats. The tumor accumulation of liposomes was also examined. The liver/tumor ratio of liposomes containing Neu5Aβ-PA was similar to that of liposomes containing GM₁ in mice and lower than that of liposomes containing GM₁ in rats.     

Brain delivery of proteins by the intranasal route of administration: A comparison of cationic liposomes versus aqueous solution formulations

The goal of this research was to evaluate the effectiveness of cationic liposomes for intranasal administration of proteins to the brain. Cationic liposomes were loaded with a model protein, ovalbumin (OVAL), and a 50 µg dose was administered intranasally to rats. In qualitative studies, liposomes were loaded with Alexa 488‐OVAL and delivery was assessed by fluorescence microscopy. By 6 and 24 h after administration, Alexa 488‐OVAL deposits were widely distributed throughout brain, with apparent cellular uptake in midbrain by 6 h after administration. In quantitative studies, liposomes were loaded with ¹¹¹In‐OVAL, and distribution to brain and peripheral tissues was monitored by gamma counting at 1, 4, 6, and 24 h after administration. The highest brain concentrations were achieved at the shortest time point, 1 h, for both liposomal and aqueous OVAL. However, the liposomes yielded higher ¹¹¹In‐OVAL concentrations in brain than ¹¹¹In‐OVAL in PBS. Moreover, a 2 µg/µL form of liposomal OVAL yielded a higher percentage of dose in brain, and a lower percentage in stomach and intestines, than twice the volume of a 1 µg/µL preparation. Cationic liposomes may provide a novel, noninvasive strategy for delivery of neuroactive proteins to the brain for treatment of central nervous system disorders. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1745–1761, 2010     

葡萄糖修饰的不同PEG作为桥联脂质体的体外特性研究

目的 制备用葡萄糖修饰以不同聚合度的PEG作为桥联的脂质体,并考察其体外特性.方法 以香豆素6为荧光探针,用薄膜分散法制备葡萄糖修饰的以PFG400、PEG800、PEG2000作为桥联的载香豆素6脂质体,用激发光散射粒度测定仪测定其粒径;用凝胶柱层析法测定其包封率;在含10%胎牛血清的磷酸盐缓冲液（PBS）中考察其稳定性;以大鼠脑毛细血管内皮细胞（BCECs）为受试细胞,对载香豆素6的不同类型脂质体进行细胞摄取的定量分析.结果 葡萄糖修饰的以PEG400、PEG800、PEG2000作为桥联的脂质体的粒径分别为（81.5±6.3）、（100.0±5.0）、（104.9±8.7）nm,多分散系数（PDI）分别为（0.252±0.016）、（0.265±0.032）、（0.289±0.013）;其包封率均〉80%;在含10%胎牛血清的PBS中具有较好的稳定性;葡萄糖修饰的以PEG800、PEG2000作为桥联的脂质体在BCECs中的细胞摄取率均高于普通脂质体.结论 本研究成功制备了葡萄糖修饰的以PEG400、PEG800、PEG2000作为桥联的脂质体,研究初步显示以PEG800、PEG2000为桥联的脂质体有一定脑靶向潜力.     

Preparation and the in-vivo evaluation of paclitaxel liposomes for lung targeting delivery in dogs

Objectives The aim of this study was to develop paclitaxel liposomes for a lung targeting delivery system. Methods The liposomes composed of Tween‐80/HSPC/cholesterol (0.03 : 3.84 : 3.84, mol/mol), containing paclitaxel and lipids (1 : 40, mol/mol), were prepared by a combination of solid dispersion and effervescent techniques, and then subjected to ultrasonication. The pharmacokinetics and biodistribution of liposomal and injectable formulation of paclitaxel in dogs were studied after intravenous administration. Key findings The mean diameter, polydispersity index, zeta‐potential and entrapment efficiency of the liposomes were 501.60 ± 15.43 nm, 0.28 ± 0.02, ?20.93 ± 0.06 mV and 95.17 ± 0.32%, respectively. The liposomal formulation kept stable for at least 3 months at 6 ± 2°C and didn't cause haemolysis. The liposome carrier decreased the area under the curve and terminal half‐life of paclitaxel compared with paclitaxel injection ranging from 0.352 ± 0.031 mg/l*h and 0.0671 ± 0.144 h to 0.748 ± 0.062 mg/l*h and 1.978 ± 0.518 h, respectively. The paclitaxel liposomes produced a drug concentration in the lung that was markedly higher than that in other organs or tissues and was about 15‐fold of that of paclitaxel injection at 2 h. Conclusions To sum up, these results demonstrated that the paclitaxel liposomes are an effective lung targeted carrier in the treatment of lung cancer.     

Efficacy of high dose-short duration ribavirin aerosol in the treatment of respiratory syncytial virus infected cotton rats and influenza B virus infected mice

Fifteen to 20 mg/ml ribavirin administered as a small particle aerosol for 10-18 h per day is currently the regimen generally used to treat experimental or naturally-occurring respiratory syncytial (RS) or influenza virus infections in humans. To determine if such prolonged treatment schedules could be reduced, cotton rats and mice were inoculated with RS or influenza B virus, respectively, and then treated with different concentrations of ribavirin small particle aerosols. Aerosols generated from reservoirs containing 60 mg/ml ribavirin given 2 h twice daily, protected cotton rats from RS virus and mice from influenza B virus as well as aerosols generated from reservoirs containing 20 mg/ml ribavirin given 11 h daily. Aerosols generated from reservoirs containing 40 or 20 mg/ml given 2 h daily were less efficacious. There was no evidence of intolerance or pulmonary histopathology in infected or uninfected animals exposed to any of the doses of ribavirin tested. These studies indicate that use of aerosols containing higher concentrations of ribavirin than generally used to treat respiratory virus diseases may permit significantly shorter treatment schedules without loss of efficacy or increase in toxicity.     

Vitamin E TPGS coated liposomes enhanced cellular uptake and cytotoxicity of docetaxel in brain cancer cells

The aim of this work was to develop a drug delivery system of liposomes, which are coated with D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), a PEGylated vitamin E, with docetaxel as a model drug for enhanced treatment of brain tumour in comparison with the nude liposomes as well as with the so-called stealth liposomes, i.e. those coated with polyethylene glycol (PEG), which have been intensive investigated in the literature. Docetaxel or coumarin-6 loaded liposomes were prepared by the solvent injection method and characterized for their particle size, polydispersity, zeta potential and drug encapsulation efficiency. C6 glioma cells were employed as an in vitro model to access cellular uptake and cytotoxicity of the drug or coumarin-6 loaded liposomes. The particle size of the PEG or TPGS coated liposomes was ranged between 126 and 191nm. High-resolution field-emission transmission electron microscopy (FETEM) confirmed the coating of TPGS on the liposomes. The IC50 value, which is the drug concentration needed to kill 50% cells in a designated time period, was found to be 37.04±1.05, 31.04±0.75, 7.70±0.22, and 5.93±0.57μg/ml for the commercial Taxotere(?), the nude, PEG coated and TPGS coated liposomes, respectively after 24h culture with C6 glioma cells. The TPGS coated liposomes showed great advantages in vitro than the PEG coated liposomes.     

Antimicrobial effectiveness of liposomal polymyxin B against resistant Gram-negative bacterial strains

Polymyxin B is a polycationic antibiotic effective in the treatment of Gram-negative bacterial infections. Systemic use of polymyxin B has been limited due to its toxicity, most notably nephrotoxicity, ototoxicity, and neuromuscular blockade. Entrapment of antibiotics in liposomes is known to enhance their antimicrobial activities while minimizing their toxic effects. In the present study, polymyxin B was incorporated into liposomes composed of either 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol (Chol) or 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and Chol. The entrapment efficiency of sonicated liposomes containing DPPC/Chol (32.1+/-2.43%) was six-fold higher than that of liposomes containing POPC/Chol (5.35+/-0.32%). On the other hand, the entrapment efficiency of extruded DPPC/Chol liposomes (3.23+/-0.46%) was about 30% less than that of liposomes composed of POPC/Chol (5.10+/-0.37%). Incubation of extruded DPPC/Chol liposomes containing polymyxin B in serum at 37 degrees C resulted in a complete release of the antibiotic into the supernatant after 3h as compared to 6h in the case of POPC/Chol liposomes. Spontaneous release of polymyxin B from DPPC/Chol liposomes incubated in saline was significantly higher (66%) than that from POPC/Chol liposomes (24%) after 48h at 37 degrees C. With respect to the antimicrobial activities of the liposomal polymyxin B formulations, the MICs of sonicated DPPC/Chol liposomes against Gram-negative strains were generally lower when compared to free polymyxin B. Immunocytochemistry and electron transmission microscopic studies revealed that the penetration of polymyxin B into a resistant strain of Pseudomonas aeruginosa was higher following its administration as a liposomal formulation as compared to its conventional form. The combination of free drug and plain liposomes had an antibacterial activity similar to that of free antibiotic. These data suggest that incorporation of polymyxin B in liposomes could be useful in the management of Gram-negative infections induced by these microorganisms.