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。     

伪三元相图法优化复方丁香油微乳制备工艺

目的应用伪三元相图法优化复方丁香油微乳的处方工艺。方法以复方丁香油为油相,蒸馏水为水相,强力搅拌,借助伪三元相图,比较微乳区域大小,以选择合适的乳化剂和助乳化剂,并确定其最佳配比。结果吐温类作乳化剂的效果明显优于司盘类,且随着吐温类其分子量的增大乳化效果也增强;助乳化剂宜选用醇类;按适当配比可制得透明均一的复方丁香油微乳。结论以吐温-80为乳化剂,1,2-丙二醇为助乳化剂,复方丁香油为油相,按6∶2∶2的比例制得复方丁香油微乳的性质最好。     

鸦胆子油自微乳化制剂的处方优化及质量评价

目的:优化鸦胆子油自微乳化制剂处方并对其质量进行评价。方法:通过可溶性实验,辅料配伍对比实验,绘制三元相图筛选鸦胆子油自微乳最佳处方,用激光粒度扫描仪测定粒径,以乳液澄明度、乳滴粒径、自乳化效率、物理稳定性为指标对其进行质量评价。结果:鸦胆子油自微乳最优处方比例为鸦胆子油0.45g,卵磷脂0.15g,IPM0.15g,RH-400.15g,甘油0.4g,测得乳滴粒径为9.2nm,自乳化时间为20.53s。结论:在37℃下加入50mL纯化水形成鸦胆子油自微乳澄清透明,物理稳定性良好。     

伪三元相图结合CCD响应面法优化辛夷油微乳处方

目的 优选辛夷油微乳处方.方法 以辛夷油为油相、蒸馏水为水相,借助伪三元相图,选择合适的乳化剂和助乳化剂及其配比范围;以油相质量分数、固定乳化剂与助乳化剂比例(Km值)为考察因素,以乳滴粒径及聚合物分散性指数(PDI)为评价指标,采用中心复合设计响应面法优选上述两因素的最佳比例.结果 优选的辛夷油微乳处方为以辛夷油为油...     

葛根素微乳的制备及质量评价

利用伪三元相图，得到空白微乳的优化处方为吐温80一甘油．油酸乙酯．水（重量比20：20：1．6：58．4）。进而制得葛根素含量约20mg／ml的载药微乳。结果表明，载药微乳和空白微乳的黏度、电导率、折光率、粒径无显著差异；载药微乳的平均粒径23．4nm。稳定性初步试验表明，制品在60℃和45001x光照条件下放置10d，含量无显著变化。     

伪三元相图法研究芦丁自微乳化释药系统的制备工艺

摘 要 目的：应用伪三元相图法优化芦丁自微乳化释药体系的处方构成。 方法: 对油相、乳化剂、助乳化剂通过溶解度试验进行初步筛选,应用水滴定法绘制伪三元相图,考察不同配方的相图行为,确定芦丁的最佳自微乳处方构成。 结果: 优化的芦丁自微乳化释药系统的处方组成为油酸 聚氧乙烯40氢化蓖麻油 无水乙醇,质量比为23∶36∶12,制备的自微乳和载药微乳澄清透明。 结论:由伪三元相图法筛选的处方制备而成的自微乳化释药系统能显著提高芦丁的溶解度。     

葛根素自微乳制剂的制备工艺研究

目的:研究制备葛根素自微乳制剂。方法:根据葛根素的饱和溶解度选取油相、乳化剂和助乳化剂,通过伪三元相图,以自乳化效率及成乳后粒径为指标,确定最佳处方。结果:最佳处方为油酸乙酯∶吐温80/蓖麻油聚氧乙烯醚40(1∶2)∶聚乙二醇400∶葛根素∶三七总皂苷=15∶35∶35∶6∶9;微乳的平均粒径为32.9nm。结论:加入三七总皂苷的葛根素自微乳粒径小,稳定性好,这为自微乳制剂的增效减毒提供了新的思路和途径。     

星点设计-效应面法优化紫杉醇自微乳给药系统

目的紫杉醇自微乳释药系统的制备优化及评价。方法通过溶解度试验、伪三元相图的绘制及星点设计-效应面法,以粒径、平衡溶解度和自乳化时间为指标,筛选最佳处方,并对紫杉醇自微乳的理化性质和体外释药进行测定。结果紫杉醇自微乳最佳处方:十四酸异丙酯为23.93%、聚氧乙烯蓖麻油为57.91%、聚乙二醇400为18.16%;其平均粒径<40 nm,自乳化时间<86 s。结论制得的紫杉醇自微乳给药系统稳定,能显著提高紫杉醇的溶解度。     

丹参酮ⅡA微乳的制备与质量评价

目的 研制丹参酮ⅡA微乳,并评价其质量.方法 通过滴定法绘制伪三元相图,筛选微乳处方;采用RP-HPLC法测定丹参酮ⅡA的含量,以外观、粒径及其分布、Zeta电位、含量为指标考察微乳的稳定性.结果 优选的处方含聚氧乙烯蓖麻油-大豆磷脂-无水乙醇-油酸乙酯(2:1:2:5)和水,所制微乳的外观均一透明,平均粒径22.1 nm,多分散指数0.262,Zeta电位-2.73 mV,载药量748.4μg·ml-1.结论 所制微乳的理化性质较稳定,为细胞药理学及体内研究奠定了基础.     

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。     

薄荷素油纳米乳的制备

目的：研究探索制备薄荷素油纳米乳的处方。方法：采用转向法制备薄荷素油纳米乳,通过滴定法绘制伪三元相图,以纳米乳区域的面积、稳定性为考察指标,筛选薄荷素油纳米乳最佳处方。通过稀释法鉴定薄荷素油纳米乳类型、透射电子显微镜观察其外观形态、激光粒度测定仪测定其粒径分布、电位。结果：薄荷素油纳米乳优选处方结果为：表面活性剂为蓖麻油聚氧乙烯醚（EL-40）、助表面活性剂为聚乙二醇400（PEG-400）,K_m为3：1,薄荷素油、复表面活性剂、蒸馏水含量为56.62%：23.67%：19.72%;所制得薄荷素油纳米乳为澄清透明,平均粒径为19.55 nm,PDI为0.183,呈正态分布,Zeta电位为3.10 mV。结论：薄荷素油纳米乳制备工艺简单,采用优选处方制备的薄荷素油纳米乳粒径小、大小均匀。     

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。     

甲氨蝶呤微乳的制备与质量评价

目的:制备甲氨蝶呤微乳并评价其质量。方法:选用无水乙醇作助表面活性剂,以甲氨蝶呤在各种油相组分中的溶解度、不同体系的最大载油量为指标,通过滴定法绘制伪三元相图,确定微乳区,筛选甲氨蝶呤微乳的最佳处方;以外观、平均粒径及其分布、Zeta电位、含量、pH值为指标进行质量评价。结果:微乳的最佳处方为聚氧乙烯氢化蓖麻油RH-40、大豆磷脂、无水乙醇、油酸乙酯(3∶1.5∶1.5∶3),其中甲氨蝶呤在大豆磷脂中的溶解度为585.95μg·mL-1,在聚氧乙烯氢化蓖麻油RH-40/大豆磷脂体系中的最大载油量为42.8%;其外观均一透明,平均粒径为25.1nm,多分散指数为0.273,Zeta电位为-1.723mV,pH值为6～7,含药量均大于94%。结论:所制制剂理化性质稳定,制备工艺简单,质量稳定易控。     

Systematic Development of Self-Emulsifying Drug Delivery Systems of Atorvastatin with Improved Bioavailability Potential

The aim of this study was to prepare and characterize a self-emulsifying drug delivery system (SEDDS) with a high drug load of poorly water-soluble atorvastatin for the enhancement of dissolution and oral bioavailability. Solubility of atorvastatin in oil, surfactant, and cosurfactant was determined. Pseudo-ternary phase diagrams were constructed by the aqueous titration method, and formulations were developed based on the optimum excipient combinations. A high drug load (10% w/w) was achieved with a combination of oleic acid, Tween 80, and polyethylene glycol 400, ensuring the maximum dissolution property (in the case of SES6). Effects of lipids and surfactants on physical properties of SEDDS such as in vitro emulsification efficiency in terms of self-emulsification time, emulsion droplet size, and percent transmittance were measured. Multiple regression analysis revealed that a higher amount of surfactants significantly increased dissolution of ATV while decreasing emulsion droplet size and emulsification time. About a four-fold increase in dissolution was achieved by SEDDS compared to pure ATV powder. Overall, this study suggests that dissolution and oral bioavailability of ATV could be improved by SEDDS technology.     

Preparation and evaluation of a microemulsion for oral delivery of berberine

The principal aim of this study was to develop an oral microemulsion formulation of berberine in order to improve its bioavailability. The Microemulsion was prepared with pharmaceutically acceptable ingredients such as oleic acid, Tween 80 and PEG400. Phase diagrams were drawn to elucidate the phase behavior of systems, which were composed of Tween 80 as surfactant and PEG400 as cosurfactant. A single isotropic region, considered to be a bicontinuous microemulsion, was detected in the pseudo ternary phase diagrams. The berberine-loaded microemulsion was characterized by viscosity, refractive index, electrical conductivity and particle size. In vivo pharmacokinetic profile and oral bioavailability were also investigated in rats. The optimized formulation was as follows: 15 wt.% oleic acid, 17 wt.% Tween-80, 17 wt.% PEG400, and 51 wt.% water. The formulated microemulsion was found to be relatively uniform in size (24.0 nm). The in vivo study indicated that the bioavailability of the oral berberine-loaded microemulsion formulation was 6.47 times greater than that of the berberine tablet suspensions. The results suggest that the microemulsion is a promising oral drug delivery system for berberine.     

水杨酸微乳的制备及质量评价

目的制备水杨酸微乳并进行质量评价。方法采用吐温-80作乳化剂,肉豆蔻异丙酯为油相,借助伪三元相图的研究手段确定乳化剂和助乳化剂的最佳配比,制成不同浓度的水杨酸微乳,并从含量测定、透光率、pH值、比重、黏度测定和稳定性方面进行了评价。结果吐温-80与1,2-丙二醇的配比为15：1,其微乳区最大,几种浓度的水杨酸制剂均能形成微乳且稳定分散于制剂中。结论微乳能增加水杨酸在制剂中的溶解度,方便于临床应用和提高了治疗效果。     

Microemulsion formulation of clonixic acid: solubility enhancement and pain reduction

Clonixic acid is currently marketed as a salt form because of its poor water-solubility. However, the commercial dosage form causes severe pain after intramuscular or intravenous injection. To improve the solubility of clonixic acid and to reduce pain on injection, clonixic acid was incorporated into oil-in-water microemulsions prepared from pre-microemulsion concentrate composed of varying ratios of oil and surfactant mixture. As an oil phase for drug incorporation, up to 14% castor oil could be included in the pre-microemulsion concentrate without a significant increase in droplet size. Both drug contents and droplet size increased as the weight ratio of Tween 20 to Tween 85 decreased. Taken together, when microemulsions were prepared from pre-microemulsion concentrate composed of 5:12:18 weight ratio of castor oil:Tween 20:Tween 85, clonixic acid could be incorporated at 3.2 mg mL(-1) in the microemulsion with a droplet size of less than 120 nm. The osmotic pressure of this microemulsion was remarkably lower than the commercial formulation, irrespective of the dilution ratios. The rat paw-lick test was used to compare pain responses among formulations. The microemulsion formulation significantly reduced the number of rats licking their paws as well as the total licking time, suggesting less pain induction by the microemulsion formulation. The pharmacokinetic parameters of clonixic acid after intravenous administration of the clonixic acid microemulsion to rats were not significantly different from those of the commercial formulation, lysine clonixinate. The present study suggests that microemulsion is an alternative formulation for clonixic acid with improved characteristics.     

Improving emulsification efficacy of lecithin by formulation design. I: Effect of adding a secondary surfactant

The objective of this study was to seek improvement in the emulsification efficacy of lecithin by formulation design. A Base Emulsion was developed containing lecithin as the primary emulsifier. The lecithin concentration and method of preparation of the Base Emulsion were optimized to obtain minimum particle size and creaming of the emulsion. Selected hydrophilic and hydrophobic synthetic surfactants were evaluated as secondary emulsifiers for their ability to reduce particle size of the Base Emulsion. The selection of type and concentration of the secondary emulsifier was done by application of the HLB method. The hydrophilic emulsifiers selected were Tween 80, Tween 20, Pluronic F68, and Pluronic F127. The hydrophobic surfactants studied included Span 20, Span 80, Pluronic P103, and Pluronic P123. The median droplet size of the Base Emulsion was 2.7 microns. Addition of the hydrophilic emulsifiers caused an increase in particle size and substantial creaming of the emulsions. Addition of three of four hydrophobic surfactants resulted in particle size reduction, but the emulsions showed substantial creaming. Span 20 was found to be the most effective secondary emulsifier. The median particle size of the emulsion was 1.7 microns. These results suggest that supplementing the hydrophilic attributes of lecithin with an appropriate type and amount of hydrophobic surfactant improves the emulsion properties by applying principles of formulation design.