雷公藤甲素自微乳给药系统的制备及其质量评价

摘 要 目的：制备雷公藤甲素自微乳给药系统,并对其药剂学性质进行评价。方法: 通过溶解度试验及伪三元相图的绘制,筛选出雷公藤甲素自微乳的处方工艺;以自微乳平均粒径和自微乳化时间进一步优化雷公藤甲素自微乳处方;并对雷公藤甲素自微乳的药剂学性质进行考察。结果: 雷公藤甲素自微乳给药系统的最优处方为：油相中链甘油三酯（MCT）20%、表面活性剂聚氧乙烯蓖麻油（EL 35）40%、助表面活性剂聚乙二醇400（PEG 400）40%。自微乳化后平均粒径为43.48 nm,自微乳化时间小于30 s。结论:雷公藤甲素自微乳平均粒径和外观形态符合制剂学要求,具有较好的缓释效果,为进一步的药效学研究奠定基础。     

HPLC法测定汉防己甲素自微乳中汉防己甲素的含量

目的 建立测定汉防己甲素自微乳含量的高效液相色谱法.方法 采用HPLC法,色谱柱为C18色谱柱,流动相为0.06％二乙胺甲醇-水(80∶20),检测波长为282nm,进样量为10μL,流速为1.0mL·min-1,柱温为30℃.结果 汉防己甲素质量浓度在0.1004mg·mL-1 ～1.004mg·mL-范围内与峰面积呈良好的线性关系y=4365774x+ 9472(r=0.999),精密度试验结果的RSD％=0.08％,稳定性试验结果的RSD为0.32％,重复性试验结果的RSD为0.35％,回收试验结果平均回收率为100.34％,RSD为0.79％.结论 该方法简便、灵敏、准确、重复性好,结果可靠,可作为汉防己甲素自微乳的含量测定方法.     

双氯芬酸钠自乳化给药系统的研制

目的研制双氯芬酸钠自乳化给药系统。方法通过测定双氯芬酸钠在各种溶剂中的平衡溶解度,选择适宜油相、乳化剂、助乳化剂,并在此基础上绘制伪三元相图。通过对各处方比例的筛选,结合各处方载药量以及所形成微乳的稳定性,确定最佳处方。结果以油相为三辛酸/癸酸甘油酯,乳化剂为Cremophor EL,助乳化剂为丙二醇,Km1为4∶1,Km2为1∶9,双氯芬酸钠在微乳中的质量浓度为25g.L-1,该处方为最佳处方。结论所研制的自乳化给药系统具有粒径小、载药量高、性质稳定的优势,可作为进一步研究的基础。     

星点设计效应面法优化汉防己碱纳米乳滴眼液的处方

目的 采用伪三元相图联合星点设计效应面法(CCD-RSM)获得汉防己碱纳米乳(Tet-ME)滴眼液的最优处方.方法 首先筛选汉防己碱在不同辅料中的溶解度,并初步评价液态脂质的成乳能力,然后采用伪三元相图法获得形成微乳的区域,通过微乳法制备Tet-ME,分别以药物/脂质(X1)、脂质/表面活性剂(X2)为考察对象,以粒径...     

盐酸齐拉西酮自微乳的制备及其体内外活性

目的制备盐酸齐拉西酮自微乳,提高其体外溶出度及其空腹口服生物利用度。方法选择对盐酸齐拉西酮溶解能力较强的油相,乳化剂和助乳化剂,观察微乳的形成并绘制伪三元相图比较微乳区域大小,通过乳化时间的测定,粒径和Zeta电位测定来确定最佳处方,测定盐酸齐拉西酮自微乳的体外溶出度以及其在Beagle犬体内药物动力学研究。结果以油酸乙酯(油相)-吐温80(乳化剂)-聚乙二醇200(助乳化剂)(质量比为30∶47∶23)时制得的自微乳经水稀释后可形成稳定的微乳,平均粒径为58.4nm,Zeta电位为-31mV。自制盐酸齐拉西酮自微乳和市售胶囊相比,其体外溶出度显著提高,达到93%。Beagle犬体内实验表明,自制盐酸齐拉西酮自微乳的吸收不受食物影响。结论盐酸齐拉西酮自微乳制备简单,微乳粒径小,可显著提高盐酸齐拉西酮的体外溶出度,及其空腹口服生物利用度。     

自微乳制剂的研究进展

目的通过查阅文献,对自微乳的制法、处方的优化及代表性研究实例三个方面,作一客观的综述。     

天山雪莲自微乳制剂研究

目的建立雪莲自微乳制剂处方。方法通过配伍实验和伪三元相图的绘制,筛选油相、乳化剂、助乳化剂的最佳配比和处方配比。结果雪莲自微乳制剂处方中油相、表面活性剂、助表面活性剂分别为:肉豆蔻酸异丙酯、司盘80-吐温80和1,2-丙二醇。制剂载药量为6.56%。结论雪莲自微乳制剂处方组成为雪莲提取物、肉豆蔻酸异丙酯、司盘80-吐温80和1,2-丙二醇。油相、乳化剂、助乳化剂质量比为5∶3.3∶1.7。     

依托泊苷微乳相图的研究

目的确定o／w型依托泊苷微乳处方。方法选用油酸、十四酸异丙酯和十六酸异丙酯作为油相，Tween80、Cremophor EL和Cremophor RH40作为表面活性剂，乙醇、1，2-丙二醇、异丙醇、甘油和PEG400为助表面活性剂，通过滴定法绘制伪三元相图，以o／w型微乳区大小为指标筛选处方。结果确定了最终空白微乳处方为Cremophor RH40：乙醇：PEG 400：水：十四酸异丙酯=19．0：19．0：19．0：38．2：4．8（w／w）。结论所选择的微乳处方可以满足依托泊苷载药量的要求。     

微乳的制备与应用

微乳是一种制备简单、热力学及动力学稳定的、液滴粒径小于100nm的特殊乳状液,作为药物载体,能够提高药物贮存稳定性和生物利用度,并且增加疗效。本文从微乳的制备方法和在药剂学中的应用情况进行综述。     

非布司他自微乳胶囊的研制

目的 制备非布司他固体自微乳制剂,提高非布司他溶解度与溶出速度.方法 通过溶解度测定,选择对非布司他溶解度较大的油相,乳化剂及助乳化剂中,并通过绘制伪三元相图,确定成乳区域,采用Design Expert 8.0.5,以自乳化时间、平均粒径、Zeta电位为评价指标优化处方.结果 制备出最佳处方油酸乙酯39.60％,Tw...     

四乙酰基葛根素自微乳化给药系统的制备及体外评价

目的筛选四乙酰基葛根素自微乳化给药系统的处方并进行体外评价。方法测定四乙酰基葛根素在各种油相、表面活性剂和助表面活性剂中的溶解度,对不同溶剂进行初步配伍研究,采用三元相图法考察不同油相、表面活性剂和助表面活性剂形成微乳的能力,绘制不同处方组成的三元相图,以微乳外观、乳化速度、乳滴粒径、载药量为指标,进一步优选处方,找出最佳的组合和处方配比,制备自微乳化液,测定四乙酰基葛根素自微乳化制剂的溶出度。结果最佳处方体系为Labrafil M1944 cs-Polyoxy 35 castor oil-Transultol P（30∶40∶30）和LauroglycolFCC-Tween 80-Transcutol P（30∶30∶40）,此处方体系能迅速乳化为外观澄清透明的微乳液,粒径分布为（21.6±5.1）、（20.2±9.8）nm,45 min内溶出度分别96.2%、96.7%。结论成功制备了四乙酰基葛根素自微乳化给药系统。     

阿托伐他汀自微乳释药系统的制备和评价

目的制备阿托伐他汀自微乳，为自微乳释药系统的处方设计和体内外评价提供参考。方法采用伪三元相图法研究不同乳化剂、助乳化剂和油相形成微乳的能力和区域，绘制不同处方组成的相图，在此基础上制备阿托伐他汀自微乳，比较温度、介质、稀释等因素对自微乳效率的影响，进行自微乳时间、所成微乳的形态、粒径分布、zeta电位、含量和稳定性等体外评价Beagle犬体内药代动力学研究。结果理想的处方经分散后可得到平均粒径在100 nm以下、呈高斯分布的微乳，稳定性好，自微乳效率高，在Beagle犬体内的吸收明显高于市售片剂。结论本文首次研制阿托伐他汀自微乳，稳定性好，在Beagle犬体内的生物利用度高。     

星点设计-效应面法优化依托泊苷自微乳化释药系统

目的 研制稳定的依托泊苷自微乳制剂并评价其质量.方法 通过溶解度试验、处方配比、三元相图的绘制及星点设计-效应面法的优化,以粒径、溶解度和zeta电位为指标,筛选各组分的最佳组合和处方配比,并对依托泊苷自微乳的理化性质和体外溶出进行测定.结果 依托泊苷自微乳最佳处方为:依托泊苷(2.0％)、Capryol 90(15.1％)、Cremophor RH40(30.4％)、Transcutol HP(52.5％),平均粒径为18.31 nm,自乳化时间＜1min,乳化后载药量＞ 25 mg· mL-1.结论 制备的依托泊苷自微乳稳定性好,载药量高.     

紫杉醇超饱和自微乳化给药系统的制备及大鼠体内药动学研究

目的:制备紫杉醇超饱和自微乳化给药系统(supersaturatable self-microemulsifying drug delivery system,S-SMEDDS),并对其在大鼠体内的药动学进行研究。方法:采用伪三元相图的方法,优化紫杉醇自微乳化给药系统(SMEDDS)的处方。18只大鼠随机分为3组,分别灌胃给予10 mg/kg紫杉醇溶液、SMEDDS和S-SMEDDS,测定紫杉醇的血药浓度c、max、AUC和tmax,计算相对生物利用度。结果:确定紫杉醇SMEDDS最优处方为:油相∶表面活性剂∶助表面活性剂=50∶33∶17。油相为Lauroglycol FCC∶橄榄油(2∶1),表面活性剂为Cremophor EL∶吐温-80(1∶1),助表面活性剂为PEG-400。S-SMEDDS在此处方基础上添加5%羟丙基甲基纤维素。稀释对制剂的粒径无显著影响。SMEDDS和S-SMEDDS的粒径分别为(92.7±47.7)和(93.6±36.8)nm,粒径分布呈高斯分布。SMEDDS和S-SMEDDS的cmax和AUC显著高于溶液剂,tmax<溶液剂,生物利用度分别为333.9%和719.3%。结论:紫杉醇S-SMEDDS的口服吸收强于溶液剂和SMEDDS。     

银杏酮酯口服自微乳化给药系统的制备

研究制备银杏酮酯口服自微乳化给药系统。采用平衡溶解度方法筛选乳化剂与助乳化剂; 采用伪三元相图法制备微乳; 采用正交法优化处方组成; 并考察自微乳化制剂的乳化效率、溶出度、稳定性与药动学研究等。结果表明, 由肉豆蔻酸异丙酯IPM、聚氧乙烯蓖麻油Cremophor EL、丙二醇与银杏酮酯组成的自微乳化给药系统遇水可自发形成粒径为20～50 nm的稳定微乳。自微乳化给药系统的乳化效率与溶出快, 且制剂稳定性高, 能提高生物利用度。制备的银杏酮酯口服自微乳化给药系统稳定有效。     

Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid Naringenin: design,characterization, in vitro and in vivo evaluation

Abstract

Naringenin (NRG), predominant flavanone in grapefruits, possesses anti-inflammatory, anti-carcinogenic, hepato-protective and anti-lipid peroxidation effects. Slow dissolution after oral ingestion due to its poor solubility in water, as well as low bioavailability following oral administration, restricts its therapeutic application. The study is an attempt to improve the solubility and bioavailability of NRG by employing self-nanoemulsifying drug delivery technique. Preliminary screening was carried out to select oil, surfactant and co-surfactant, based on solubilization and emulsification efficiency of the components. Pseudo ternary phase diagrams were constructed to identify the area of nanoemulsification. The developed self-nanoemulsifying drug delivery systems (SNEDDS) were evaluated in term of goluble size, globule size distribution, zeta potential, and surface morphology of nanoemulsions so obtained. The TEM analysis proves that nanoemulsion shows a droplet size less than 50?nm. Freeze thaw cycling and centrifugation studies were carried out to confirm the stability of the developed SNEDDS. In vitro drug release from SNEDDS was significantly higher (p?<?0.005) than pure drug. Furthermore, area under the drug concentration time-curve (AUC_0–24) of NRG from SNEDDS formulation revealed a significant increase (p?<?0.005) in NRG absorption compared to NRG alone. The increase in drug release and bioavailability as compared to drug suspension from SNEDDS formulation may be attributed to the nanosized droplets and enhanced solubility of NRG in the SNEDDS.     

Preparation and in vivo evaluation of SMEDDS (self-microemulsifying drug delivery system) containing fenofibrate

The present work was aimed at formulating a SMEDDS (self-microemulsifying drug delivery system) of fenofibrate and evaluating its in vitro and in vivo potential. The solubility of fenofibrate was determined in various vehicles. Pseudoternary phase diagrams were used to evaluate the microemulsification existence area, and the release rate of fenofibrate was investigated using an in vitro dissolution test. SMEDDS formulations were tested for microemulsifying properties, and the resultant microemulsions were evaluated for clarity, precipitation, and particle size distribution. Formulation development and screening was done based on results obtained from phase diagrams and characteristics of resultant microemulsions. The optimized formulation for in vitro dissolution and pharmacodynamic studies was composed of Labrafac CM10 (31.5%), Tween 80 (47.3%), and polyethylene glycol 400 (12.7%). The SMEDDS formulation showed complete release in 15 minutes as compared with the plain drug, which showed a limited dissolution rate. Comparative pharmacodynamic evaluation was investigated in terms of lipid-lowering efficacy, using a Triton-induced hypercholesterolemia model in rats. The SMEDDS formulation significantly reduced serum lipid levels in phases I and II of the Triton test, as compared with plain fenofibrate. The optimized formulation was then subjected to stability studies as per International Conference on Harmonization (ICH) guidelines and was found to be stable over 12 months. Thus, the study confirmed that the SMEDDS formulation can be used as a possible alternative to traditional oral formulations of fenofibrate to improve its bioavailability.     

苦参碱固体自微乳制剂的制备及其评价

目的 制备苦参碱固体自微乳颗粒,并对其进行质量评价.方法 通过固体吸附材料的优选,制备了苦参碱固体自微乳颗粒,建立了HPLC法测定颗粒中苦参碱及其体外溶出度的方法;对溶解后微乳的类型、pH值、Zeta电位、粒径进行研究.结果 选择微粉硅胶与甘露醇质量比2∶1为固体吸附材料,每克苦参碱微乳液需加微粉硅胶0.42 g,微晶纤维素0.21 g,50℃恒温干燥后成淡黄色的苦参碱自微乳颗粒,遇水快速形成澄明的液体,平均粒径79 nm,pH值为7.95,Zeta电位-1.34 mV,载药量23.51 mg/g,45 min内累积溶出94.2％以上.结论 苦参碱固体自微乳的制备工艺简单,制剂稳定,可为水难溶性药物的开发提供一个新方法、新思路.