醋酸泼尼松龙醇质体的制备及其药剂学性质考察

目的:制备醋酸泼尼松龙醇质体并考察其药剂学性质。方法:采用乙醇注入法制备醇质体。以包封率为指标,以处方中药物与大豆磷脂质量比(A)、胆固醇与大豆磷脂质量比(B)、无水乙醇占处方总量的百分比(C)为考察因素进行正交设计优化处方;考察优化后处方所制醇质体的形态、粒径、Zeta电位、包封率、稳定性等,差示量热分析法考察其热力学特性。结果:最佳处方为平均A包1:封20率,B为1(:766、.C793±0%0.2;9以)%此,处贮方藏制30备d的稳醇定质性体较外好形。圆差整示光量滑热,分平析均法粒结径果为(表2明78,.醋5±酸4泼6.7尼)松nm龙,Z以et无a电定位形为状(态-包31封.6于±醇0.0质4)体m中V,。结论:醋酸泼尼松龙醇质体制备工艺简单,优化处方所制制剂药剂学性质符合要求。     

去氢骆驼蓬碱脂质体制备工艺优化及抗肝癌活性

目的 制备去氢骆驼蓬碱脂质体并对其制备工艺进行优化，评价脂质体的相关表征及对肝癌细胞的毒性。方法 用薄膜水化法制备去氢骆驼蓬碱脂质体。以包封率作为评价指标，以大豆卵磷脂和药物的质量比、大豆卵磷脂与胆固醇的质量比和超声时间作为评价因素对脂质体包封率的影响。并对脂质体的粒径、Zeta电位、外观和稳定性进行评价。CCK-8法对比去氢骆驼蓬碱和去氢骆驼蓬碱脂质体的抗肝癌细胞增殖活性。结果 最优制备工艺：大豆卵磷脂和药物的质量比为11.4：1，大豆卵磷脂与胆固醇的质量比为4.4：1，超声时间为33 min。在此条件下制备的脂质体的包封率为81.88%，粒径为143.65 nm，Zeta电位为-12.68 mV，低温环境稳定性良好，具有缓释效应。去氢骆驼蓬碱脂质体的抗肝癌细胞增殖活性大于裸药。结论 所制得的去氢骆驼蓬碱脂质体包封率和稳定性均符合标准。将去氢骆驼蓬碱制备成为脂质体能提高其抗肝癌细胞增殖活性。     

Increasing bioavailability of silymarin using a buccal liposomal delivery system: preparation and experimental design investigation

Silymarin is a natural lipotropic agent of low bioavailability from oral products. The aim of our study is to prepare buccal liposomal delivery system of silymarin with higher bioavailability. The effect of lecithin:cholesterol molar ratio on the percentage drug encapsulated was investigated. The influence of fluctuating the amount of added drug was also determined. The effect of additives such as positive charge inducer, negative charge inducer and surfactants was studied using two different 2(3) full factorial designs. Furthermore, additives used to optimize liposomal product were also investigated for their optimal concentrations, release properties and in vitro permeation and absorption through chicken cheek pouch. Optimal liposomal encapsulation efficiency was found at 7:4 lecithin to cholesterol molar ratio. A decrease in entrapment efficiency with increasing cholesterol content was observed. Tween 20 or Tween 80 beyond 0.5 molar ratio decreased the entrapment efficiency. Positively charged liposomes showed superior entrapment efficiency over neutral and negatively charged liposomes. Release studies as well as permeation and absorption studies showed that hybrid liposomes prepared according to formula 3 containing lecithin, cholesterol, stearyl amine and Tween 20 in 9:1:1:0.5 molar ratio, respectively, gave the best drug absorption and permeation. It showed steady state permeation through chicken cheek pouch for 6h. This is expected to improve the bioavailability of silymarin in the developed liposomal buccal delivery system, as the results show an increase in drug penetration compared to free drug powder.     

Proniosomes as a drug carrier for transdermal delivery of ketorolac.

Niosomes are nonionic surfactant vesicles that have potential applications in the delivery of hydrophobic and hydrophilic drugs. Permeation of a potent nonsteroidal anti-inflammatory, ketorolac, across excised rabbit skin from various proniosome gel formulations was investigated using Franz diffusion cells. Each of the prepared proniosomes significantly improved drug permeation and reduced the lag time (P<0.05). Proniosomes prepared with Span 60 provided a higher ketorolac flux across the skin than did those prepared with Tween 20 (7- and 4-fold the control, respectively). A change in the cholesterol content did not affect the efficiency of the proniosomes, and the reduction in the lecithin content did not significantly decrease the flux (P>0.05). The encapsulation efficiency and size of niosomal vesicles formed by proniosome hydration were also characterized by specific high performance liquid chromatography method and scanning electron microscopy. Each of the prepared niosomes achieved about 99% drug encapsulation. Vesicle size was markedly dependent on the composition of the proniosomal formulations. Proniosomes may be a promising carrier for ketorolac and other drugs, especially due to their simple production and facile up.     

Encapsulation efficiency of water-soluble and insoluble drugs in liposomes prepared by the microencapsulation vesicle method

The microencapsulation vesicle (MCV) method is a liposome preparation technique that reproducibly produces liposomes with homogeneous particle sizes with a high encapsulation efficiency. Liposomes encapsulating water-soluble drugs, lipophilic drugs and an amphiphilic drug were prepared by the MCV method and the encapsulation efficiency of the drugs was examined. Three kinds of egg yolk lecithin with different iodine values, i.e., purified egg yolk lecithin (PEL), partially hydrogenated purified egg yolk lecithin (R-20) and completely hydrogenated purified egg yolk lecithin (R-5), were used for membrane materials in order to explore the possible effects of membrane rigidity or surface area on the encapsulation efficiency of the drug. Water-soluble 5-fluorouracil showed 12-15% encapsulation efficiency, which was higher than those reported in the literature (less than 10%). With the MCV method, theoretically the initial drug-containing water phase was always separated from the dispersion medium by the lecithin-containing oil phase, which was advantageous to maintaining a higher encapsulation efficiency of the water-soluble drug. The encapsulation efficiency of lipophilic ibuprofen and flurbiprofen was around 90%. As for ketoprofen and liposomes were not formed when using hydrogenated egg yolk lecithin R-5, while the encapsulation efficiency using PEL or R-20 was around 80%. Amphiphilic amitriptyline hydrochloride resulted in a slightly higher encapsulation efficiency when dissolved in the water than the chloroform. Among the three kinds of lecithin, the most unsaturated PEL tended to show a higher encapsulation efficiency, probably due to differences in the packing geometry of the hydrophobic carbon chains in the membrane bilayer. The encapsulation efficiency of these drugs strongly correlated to the logP(octanol/water) and also tended to correlate to the logP(chloroform/water) for the order of the logP(chloroform/water) was almost the same as the order of the logP(octanol/water) in the drugs examined. As far as the results of this study, the logP(octanol/water) was considered to be a better indicator of the encapsulation efficiency of a drug in the MCV method.     

Stability and drug release properties of liposomes containing cytarabine as a drug carrier

Liposomes were studied as a drug delivery system. Multilamellar vesicles, small unilamellar vesicles and large unilamellar vesicles containing cytarabine were prepared using egg yolk lecithin and cholesterol. Large unilamellar vesicles showed the highest encapsulation efficiency of all and their encapsulation efficiency increased as the buffer volume decreased. Cholesterol increased the stability of liposomal drug products as drug carriers and reduced the permeability of drug across the liposomal membrane. The release rate of cytarabine increased with incubation temperature and decreased with cholesterol incorporation in liposomal membrane. The release mechanism of cytarabine from large unilamellar vesicles in vitro was chiefly due to simple diffusion across the liposomal membrane rather than liposomal rupture.     

正交试验优选盐酸川芎嗪脂质体的制备工艺

目的:优选盐酸川芎嗪脂质体的制备工艺。方法:以乙醚注入法制备川芎嗪脂质体,采用正交试验,以包封率为指标,以药物与大豆卵磷脂用量比、PBS缓冲液的pH值、胆固醇与大豆卵磷脂用量比、乙醚与PBS缓冲液用量比为考察因素,优选制备工艺。结果:最佳工艺条件为药物:大豆卵磷脂为1:12,PBS缓冲液pH为7.5,胆固醇:大豆卵磷脂为1:2,乙醚:PBS缓冲液为1:2。结论:该制备工艺可行、稳定、重现性好,可为工业化生产提供理论依据。     

克班宁长循环脂质体的制备工艺

目的:研究克班宁长循环脂质体的处方筛选和制备工艺。方法:采用硫酸铵梯度法制备克班宁长循环脂质体,以包封率和载药量为评价指标,采用葡聚糖凝胶过滤法分离脂质体,紫外分光光度法测定克班宁含量,采用正交设计优化制备工艺。结果:最佳工艺为:药脂比为1:6,胆固醇与磷脂比为9:12,0.15 mol·L^-1的硫酸铵溶液,以PBS液(pH7.4)为透析介质,在40 ℃水浴,40 r·min^-1条件下孵化20 min。结论:硫酸铵梯度法制备的克班宁长循环脂质体处方合理,工艺可行,包封率较高。     

盐酸小檗碱脂质体制备工艺研究

目的用薄膜蒸发法制备盐酸小檗碱脂质体。方法用离子交换树脂法测定脂质体包封率。以盐酸小檗碱脂质体包封率为指标,考察脂质体包封率的影响因素。结果制备盐酸小檗碱脂质体的最佳工艺条件为孵化温度65℃,孵化时间40min;此时包封率最高,且随着卵磷脂浓度的变化而变化。结论薄膜蒸发法制备的盐酸小檗碱脂质体粒径小、包封率高,条件易掌握,故该法可作为盐酸小檗碱脂质体的常规制备方法。     

西罗莫司脂质体的制备及处方因素考察

目的 制备西罗莫司脂质体并对处方进行筛选,以期得到高包封率的脂质体制剂.方法 选用乙醇注入法制备西罗莫司脂质体,微柱离心-HPLC法测定包封率,以包封率为评价指标,考察磷脂浓度、磷脂胆固醇质量比、药脂比、水相介质pH等因素对脂质体的影响,在此基础上运用正交设计对处方进行优化.结果 正交试验结果表明磷脂浓度为4%,磷脂与胆固醇质量比例为8:1,药物磷脂质量比为1:20,水相pH为7.4为最佳处方,制得的脂质体包封率为(82.11±2.13)%.结论 优选出最佳处方,制得的西罗莫司脂质体包封率高,重现性好.     

高乌甲素脂质体凝胶制备工艺筛选实验研究

目的：研究乙醇注入法制备高乌甲素脂质体凝胶的工艺。方法：采用单因素实验分析药脂比、磷脂胆固醇比、水化液pH、水化温度筛选影响包封率及载药量的因素,再采用正交试验优选最佳处方;制备得到高乌甲素脂质体后,单因素实验筛选最佳卡波姆用量及pH,得到最适宜脂质体凝胶配方。结果：采用正交试验法确定高乌甲素脂质体最佳处方工艺组合为卵磷脂：胆固醇为6∶1、药脂比为1∶10、水化温度为55 ℃,水化液pH值为7.0,该处方制备的脂质体包封率高,粒径分布均匀;当卡波姆-940用量为1%、在pH 6~7时,所制备的高乌甲素脂质体凝胶易涂布、黏度适宜。结论：制备的高乌甲素脂质体凝胶工艺简单可行,包封率较高,可以进一步研究。     

棓丙酯脂质体的制备与表征

目的制备棓丙酯脂质体,并对其进行理化性质的表征和释放度的评价。方法采用薄膜分散法制备棓丙酯脂质体,超滤离心法测定脂质体的包封率,正交设计优化处方,并对其包封率、粒径、Zeta电位、形态及体外释放行为进行综合评价。结果正交设计优化最终处方为磷脂浓度5 mg.mL-1、药脂比1∶5、磷脂胆固醇比5∶1、水化介质离子强度20 mmol.mL-1,所得脂质体包封率为89.6%、粒径为181.3 nm、Zeta电位为-21.8 mV、4 h体外释放达到80%。结论制备的棓丙酯脂质体包封率高,粒径小而均一,体外释放完全。     

Liposomes for Topical Use: A Physico-Chemical Comparison of Vesicles Prepared from Egg or Soy Lecithin

Developments in nanotechnology and in the formulation of liposomal systems provide the opportunity for cosmetic dermatology to design novel delivery systems. Determination of their physico-chemical parameters has importance when developing a nano-delivery system. The present study highlights some technological aspects/characteristics of liposomes formulated from egg or soy lecithins for topical use. Alterations in the pH, viscosity, surface tension, and microscopic/macroscopic appearance of these vesicular systems were investigated. The chemical composition of the two types of lecithin was checked by mass spectrometry. Caffeine, as a model molecule, was encapsulated into multilamellar vesicles prepared from the two types of lecithin: then zeta potential, membrane fluidity, and encapsulation efficiency were compared. According to our observations, samples prepared from the two lecithins altered the pH in opposite directions: egg lecithin increased it while soy lecithin decreased it with increased lipid concentration. Our EPR spectroscopic results showed that the binding of caffeine did not change the membrane fluidity in the temperature range of possible topical use (measured between 2 and 50 °C). Combining our results on encapsulation efficiency for caffeine (about 30% for both lecithins) with those on membrane fluidity data, we concluded that the interaction of caffeine with the liposomal membrane does not change the rotational motion of the lipid molecules close to the head group region. In conclusion, topical use of egg lecithin for liposomal formulations can be preferred if there are no differences in the physico-chemical properties due to the encapsulated drugs, because the physiological effects of egg lecithin vesicles on skin are significantly better than that of soy lecithin liposomes.     

硫酸阿米卡星多囊脂质体的制备及评价

目的 制备硫酸阿米卡星多囊脂质体(amikacin sulfate multivesicular liposomes, AMK-MVLs),对其进行质量评 价,并考察了其体外抗菌活性。方法 采用复乳法制备AMK-MVLs混悬液Ⅰ,Box-Behnken效应面法优化筛选最佳处方,采 用生理盐水洗涤后调整药物浓度得AMK-MVLs混悬液。采用光学显微镜、激光粒度仪、差示扫描量热(differential scanning calorimeter,DSC)考察制剂的理化性质,采用透析法考察其体外释放规律,通过微量稀释法初步考察其体外抗菌活性。结 果 优化得到AMK-MVLs混悬液Ⅰ的最佳处方为：大豆磷脂与胆固醇质量比为1.91:1,三油酸甘油酯用量为1.02%,PVA用量为 0.62%。AMK-MVLs呈堆叠有无数囊泡的非同心球状,AMK-MVLs混悬液包封率(87.12±1.55)%,平均粒径为11.93 μm。DSC 结果表明,AMK以无定型状态存在于脂质体内。体外释放结果显示AMK-MVLs混悬液在72 h时释药约80%。体外溶血实验表 明,AMK-MVLs脂质体粒子浓度低于400 μg/mL时无溶血风险。体外抗菌实验结果显示,相较于AMK溶液,AMK-MVLs混悬液对E. coli、 P. aeruginosa、S. aureus 3种细菌具有更好的抗菌效果。结论 成功制备了一种硫酸阿米卡星多囊脂质体,其粒径分布均匀、包 封率高,释药规律符合Higuchi动力学模型,具有增强的抗菌活性。     

卵磷脂质量对甲氨喋呤(MTX)脂质体包裹率的影响

本文研究了卵磷脂的理化性质与MTX脂质体包裹率的关系。分别测定了两种卵磷脂(大豆卵磷脂、蛋黄卵磷脂)的氧化指数、碘价、紫外吸收光谱及薄层层析,并用具有不同氧化指数的卵磷脂用二次乳化蒸发法制备MTX脂质体,测定它们包裹MTX的百分率。初步表明:卵磷脂对药物包裹率随其氧化指数的升高而降低,同时薄层层析的杂质点亦增多。实验结果提示,用氧化指数在0.2以下,碘价在60左右,以及薄层层析一个点的卵磷脂制备MTX脂质体可以得到较高的包裹率。     

维A酸脂质体的制备工艺研究

目的:提供一种制备稳定维A酸脂质体的新方法。方法:采用乙醇注入法制备维A酸脂质体,通过单因素试验和四因素三水平正交试验,以包封率为主要指标,优选药脂比、磷脂与胆固醇之比、水合介质(0.01 mol/L磷酸盐缓冲液)的pH和用量;并制备样品进行稳定性考察。结果:以药脂比为1∶10(维A酸用量1.0 mg),磷脂与胆固醇之比为4∶1,水合介质的pH为6.5、用量为30ml为最佳工艺;所制维A酸脂质体的包封率约为80%,平均粒径约为150 nm。在室温条件下密封放置10 d及4℃下保存6个月,其平均粒径及包封率差异无统计学意义(P>0.05)。结论:该制剂制备工艺简单可行;制剂处方合理,包封率较高,且在短期内稳定性良好。     

正交试验优选槲皮素长循环脂质体制备工艺

目的：研究以山嵛酸甘油酯、大豆卵磷脂和胆固醇为油相,泊洛沙姆、聚乙二醇-二硬脂酰磷脂酰乙醇胺和吐温-80作为水相的槲皮素长循环脂质体的制备工艺。方法：采用正交试验法,以纳米脂质体包封率和载药量等作为评价指标,采用多指标综合分析方法优选槲皮素长循环脂质体油相与水相的最佳比例。结果：槲皮素长循环脂质体的最佳制备工艺为：水：油相比例为1．5：1．0,水相之间（泊洛沙姆：PEG2000-DSPE：吐温-80）比例为1：1：1．0,油相之间（山嵛酸甘油酯：大豆卵磷脂：胆固醇）比例为1：2：1,以此制备工艺制得的长循环脂质体包封率和载药量较为理想。结论：该优选工艺制备槲皮素长循环脂质体,方法简易、可行。     

依托泊苷固体脂质纳米粒的研制

目的:制备依托泊苷固体脂质纳米粒(ET-SLN)并考察其药剂学性质。方法:采用乳化-超声分散法制备ET-SLN,以单硬脂酸甘油酯(A)、大豆磷脂(B)、泊洛沙姆188(C)、依托泊苷(D)的处方用量为考察因素,包封率为指标设计正交试验,筛选最优处方。考察纳米粒的粒径、表面电位、包封率、体外释放情况等。结果:A、B、C、D分别为0.020、0.010、0.015、0.015mg;所制纳米粒平均粒径(83±0.5)nm,表面电位(-23±0.3)mV,包封率81.2%,可持续48h缓释。结论:所制ET-SLN符合药剂学性质要求。     

大黄素传递体的制备和质量评价研究

目的 制备大黄素传递体,并建立其有关质量评价标准.方法 采用薄膜超声法制备大黄素传递体,以包封率为考察指标,通过单因素考察和正交实验设计优选最佳处方和工艺;采用Zetasizer电位及纳米粒度分析仪测定其Zeta电位并分析其大小,用紫外分光光度法测定药物的包封率等.结果 大黄素传递体最佳制备配方为去氧胆酸钠与磷脂比为1∶8,胆固醇与磷脂比为1∶3,维生素E与磷脂比为1∶20,大黄素与磷脂比为1∶6.所得大黄素传递体Zeta电位-15.11 mV,平均粒径为292.2 nm,球形圆整,大小均匀.在检测波长为435 nm处的吸光度(A)与药物浓度[C,(g/L)]的标准曲线方程为A=50.485C -0.0913(R2=0.9991),测得平均包封率为(69.35 ±0.25)％.结论 该传递体制备处方精确合理、工艺简单可行,所得传递体带负电,粒径较小且分布均匀,包封率高且稳定性好.     

苯丁酸氮芥脂质体的制备及处方因素考察

目的 制备苯丁酸氮芥脂质体并优化其处方。方法 薄膜超声分散法制备苯丁酸氮芥脂质体,采用微柱离心-HPLC法测定其包封率,以包封率为考察指标,研究膜材比、药脂比、水相介质pH值以及磷脂浓度等因素对脂质体包封率的影响;通过正交试验对处方进行优化,并进行质量评价。结果 苯丁酸氮芥脂质体优化后的制备处方为胆固醇与磷脂质量比1∶3、药脂比1∶10、水相介质pH值为7.4、磷脂浓度为0.3%。按该处方制得的苯丁酸氮芥脂质体包封率>87%,平均粒径为84.71 nm,PDI为0.167。结论 优选处方稳定可行,制备的苯丁酸氮芥脂质体包封率高、粒径小且均匀。