依托泊苷口服微乳的制备及质量评价

目的 研制O/W型依托泊苷口服微乳制剂并评价其质量.方法 通过相图筛选处方,并考察最大载药量及所制微乳的性质.结果 空白微乳最终处方为;Cremophor RH40-乙醇-PEG 400-水-十四酸异丙酯(19.0;19.0;19.0;38.2;4.8),依托泊苷的含量为10 mg·ml-1,平均粒径为34.6 nm.结论 所制备的O/W型微乳能显著提高依托泊苷的溶解度,且制备简单,质量稳定.     

o/w型、w/o型葛根素口服微乳的制备及质量评价

目的研制o/w型、w/o型葛根素口服微乳制剂并进行质量评价。方法通过相图研究进行处方筛选,并考察最大载药量。对制备的o/w型、w/o型微乳的性质进行考察。结果得到空白微乳的最终处方(重量比)为:o/w型微乳:RH∶1,2-丙二醇∶EO∶水=12.6∶6.3∶2.1∶79.0;w/o型微乳:PC∶无水乙醇∶EO∶水=45∶22.5∶27.5∶5。葛根素含量均为30 mg.mL-1,平均粒径分别为23.4和46.2 nm。结论o/w型、w/o型微乳均能显著提高葛根素溶解度,且制备简单,质量稳定。     

Preparation and evaluation of microemulsion of vinpocetine for transdermal delivery

Poorly soluble vinpocetine was selected as the model drug to prepare a microemulsion in order to increase solubility and in vitro transdermal delivery of the drug. Oleic acid was chosen as the oil phase due to its excellent solubilizing capacity. PEG-40 hydrogenated castor oil (Cremophor RH40) was employed as a surfactant (S) and purified diethylene glycol monoethyl ether (Transcutol P) was used as a cosurfactant (CoS). The effects of diverse types of oil, different weight ratios of surfactant to cosurfactant (S/CoS) on the solubility and permeation rate of vinpocetine were investigated. The optimized microemulsion consisted of 1% vinpocetine, 4% oleic acid, 20% Cremophor RH40, 10% Transcutol P and 65% distilled water (w/w), in which drug solubility was about 2,100 fold compared to that in water and the apparent permeation rate across the excised rat skin was 15.0 +/- 2.5 microg/cm2/h. Finally the physicochemical properties of the optimized microemulsion including pH, viscosity, refractive index, conductivity and particle size distribution were examined, which showed stable behavior after more than 12 months at ambient temperature. The irritation study showed that optimized microemulsion was a safe transdermal delivery system.     

Preparation and evaluation of aceclofenac microemulsion for transdermal delivery system

To develop novel transdermal formulation for aceclofenac, microemulsion was prepared for increasing its skin permeability. Based on solubility and phase studies, oil and surfactant was selected and composition was determined. Microemulsion was spontaneously prepared by mixing ingredients and the physicochemical properties such was investigated. The mean diameters of microemulsion were approximately 90 nm and the system was physically stable at room temperature at least for 3 months. In addition, the in vitro and in vivo performance of microemulsion formulation was evaluated. Aceclofenac was released from microemulsion in acidic aqueous medium, and dissolved amounts of aceclofenac was approximately 30% after 240 min. Skin permeation of aceclofenac from microemulsion formulation was higher than that of cream. Following transdermal application of aceclofenac preparation to delayed onset muscle soreness, serum creatine phosphokinase and lactate dehydrogenase activity was significantly reduced by aceclofenac. Aceclofenac in microemulsion was more potent than cream in the alleviation of muscle pain. Therefore, the microemulsion formulation of aceclofenac appear to be a reasonable transdermal delivery system of the drug with enhanced skin permeability and efficacy for the treatment of muscle damage.     

Development of propofol-loaded microemulsion systems for parenteral delivery

The aim of the present study was to develop the aqueous parenteral formulation containing propofol using o/w microemulsion systems. Propofol itself was chosen as the oil phase and its content was fixed to 1%, w/w. Pseudoternary phase diagrams were constructed to obtain the concentration range of surfactant and cosurfacatnt and the optimum ratio between them for microemulsion formation. Consequently, the suitability of the chosen microemulsion system as a parenteral formulation was evaluated from the stability and hemolysis tests on that. Among the surfactants and cosurfactants screened, the mixture of Solutol HS 15-ethyl alcohol (5/1) showed the largest o/w mocroemulsion region in the phase diagram. When 1% (w/w) of propofol was solubilized with 8% (w/w) of Solutol HS 15-ethyl alcohol (5/1), the average droplet size (150 nm) and the content of propofol in the systems were not significantly changed at 40 degrees C for 8 weeks. The hemolysis test showed that this formulation was nontoxic to red blood cells. In conclusion, propofol was successfully solubilized with the o/w microemulsion systems.     

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.     

Preparation and evaluation of dl-praeruptorin A microemulsion based hydrogel for dermal delivery

Abstract

The purpose of the present investigation was to develop and optimize the microemulsion (ME) as a transdermal system for Pd-Ia, a poor water soluble and low bioavailable drug. The pseudo-ternary phase diagrams were constructed for various ME formulations including oleic acid as the oil phase, Cremophor RH40 as the surfactant, ethanol as the cosurfactant, and water. The maximum cumulative amount permeated through rat abdominal skins per unit area in 32?h (Q₃₂), and the maximum flux were evaluated using the Franz diffusion cell in order to optimize the ME formulation. The results indicated that the optimized ME formulation was composed of oleic acid (5%, W/W), Cremophor RH40 (13.33%, W/W), ethanol (26.67%, W/W), and water (55%, W/W); the maximum cumulative amount of Pd-Ia was 354.330?±?12.006?μg?cm^?2, the maximum flux was 11.467?±?0.500?μg?cm^?2?h^?1. ME-gel was administered transdermally to rats. The mean plasma concentration of Pd-Ia following transdermal application of ME-gel could be maintained for 32?h at least and the half-life was evidently prolonged. It shows that the ME-gel could be a promising vehicle for dermal delivery of Pd-Ia.     

Formulation and evaluation of flurbiprofen-loaded genipin cross-linked gelatin microspheres for intra-articular delivery

Oral and parenteral formulations are challenging to produce therapeutic concentration of flurbiprofen in the joints. This encourages for the development of formulation for long term drug retention in the joint through intra-articular (i. a.) administration. In this study, genipin cross-linked gelatin microspheres of flurbiprofen were prepared for i. a. delivery. The microspheres were prepared using emulsification-homogenization-cross-linking method by changing the experimental variables such as concentration of cross-linker, cross-linking time and cross-linking temperature. The microspheres showed drug entrapment up to 76.19% with a mean particle size range of 5.91–8.19 µm. The degree of cross-linking and water-soluble fraction were 8.27–59.33% and 12.29–81.23%, respectively. SEM confirmed smooth surface and spherical shape of the microspheres. FTIR and ¹³C-NMR confirmed cross-linking of gelatin by genipin. No chemical change in encapsulated drug was observed by FTIR and TGA. DSC and XRD indicated the molecular dispersion of drug within microspheres. Optimized microspheres could prolong the drug release for more than 108?h with anomalous transport. Histopathology confirmed the biocompatibility of microspheres in the rat (Wistar) knee joint. After 96?h of i. a. injection, significant higher amount (42.56%) of administered drug in cross-linked microspheres was recovered than uncross-linked microspheres (8.27%) confirming better drug retention efficiency (p < 0.01).     

Development and evaluation of artemether parenteral microemulsion

The objective of the present investigation was to develop a parenteral microemulsion delivering artemether, a hydrophobic antimalarial drug and to evaluate antimalarial activity of the microemulsion in comparison to the marketed oily injection of artemether (Larither^®). The microemulsion was evaluated for various parameters such as globule size, ability to withstand centrifugation and freeze-thaw cycling and effect of sterilization method on the drug content and globule size. The in vivo antimalarial activity of the microemulsion was evaluated in P. berghei infected mice in comparison to the Larither^;. The stability of the microemulsion was evaluated at 5º for 1 month. The microemulsion exhibited globule size of 113 nm and it could successfully withstand centrifugation and freeze-thaw cycling. The method of sterilization did not have any significant effect on the artemether content and globule size of the microemulsion. The microemulsion showed around 1.5-fold higher antimalarial activity and higher survival as compared to that of marketed artemether injection Larither^® and it showed a good stability at the end of 1 month.     

Preparation and evaluation of andrographolide-loaded microemulsion

Andrographolide has a low aqueous solubility and oral bioavailability, which limits its clinical application. Reform the dosage forms of andrographolide to improve its aqueous solubility and oral bioavailability. The formulation, characterisation, stability, anti-inflammatory effect, pharmacokinetics and oral toxicity of andrographolide-loaded microemulsion, were studied. An formulation of O/W microemulsion consisting of an oil phase of isopropyl myristate, a surfactant phase of Tween 80, a co-surfactant of alcohol, and water was found to be ideal, with mean droplet size of 15.9?nm, a high capacity of solubilisation for andrographolide (8.02?mg?mL^?1). Such an andrographolide-loaded microemulsion is stable by monitoring the time, temperature and gravity-dependent change, and has a much better anti-inflammatory effect and a higher biological availability than andrographolide tablets. Besides, it also shows a very low acute oral toxicity. The andrographolide-loaded microemulsion is a promising dosage form of andrographolide.     

酮康唑微乳的制备及其质量评价

目的制备酮康唑微乳并进行质量评价。方法以肉豆蔻酸异丙酯(isopropyl myristate,IPM),中链甘油三酯(medium chain triglycerides,MCT)为油相,以聚氧乙烯蓖麻油(polyoxyethylenated castor oil,EL-40)或Tween80为乳化剂,分别以乙醇、1,2-丙二醇、聚乙二醇400(polyethylene glycol400,PEG400)、甘油为助乳化剂,采用加水滴定法,绘制伪三元相图,以所形成的微乳区域大小为评价指标,筛选出酮康唑微乳的最佳处方。考察所制微乳的形态、粒径及其分布、稳定性和体外经皮透过性。结果最优处方为:按质量分数取IPM 12.0%、EL-40 27.0%、PEG400 9.0%、水50.5%、酮康唑1.5%。所制备的酮康唑微乳澄清透明,透射电子显微镜下呈圆整的球形,平均粒径为36.7nm、黏度为141 mPa·s、pH值为6.66,对热、光照稳定;其透皮速率显著大于酮康他索乳膏。结论酮康唑微乳质量稳定,此微乳体系对酮康唑的透皮具有促渗作用。     

杨梅素微乳的制备及质量评价

目的制备杨梅素微乳,并评价其质量。方法选择适宜的油相、表面活性剂和助表面活性剂,利用伪三元相图筛选微乳处方,研制出适合经口给药的微乳制剂;采用HPLC法测定杨梅素的含量,并对微乳的类型、载药量、体外释放等进行考察。结果优选处方为聚山梨酯80-聚山梨酯20-乙醇-油酸-pH 6.5磷酸缓冲液的质量比20∶10∶15∶5∶50,杨梅素质量分数为2%。所制微乳外观透明,平均粒径为(56.3±8.7)nm,zeta电位为-2.73 mV,电导率为13.27 mS.m-1。载药微乳在不同pH值环境下对药物有良好的释放效果。结论通过优化处方制备的杨梅素微乳具有较稳定的理化性质,HPLC法可以有效、准确的测定杨梅素微乳的含量,并且微乳载药系统有良好的释药效果。     

微乳型丙泊酚纳米注射液的制备与评价

目的:制备微乳型丙泊酚纳米注射液,并对其进行体内外评价,为新型微乳型纳米注射液研究提供参考。方法:使用可注射用乳化剂和油制备丙泊酚纳米注射液,旋转黏度计测定其黏度,动态光散射法测定其粒径和Zeta电位,透射电镜测定其显微外观,透析法测定其游离药物浓度,并研究其体外溶血性和Beagle犬体内药动学性质。结果:黏度为1.5×10-3 Pa.s,粒径为(22.7±10.2)nm,Zeta电位为-5.82 mV;透射电镜照片显示微乳粒子外观近球状,游离药物浓度为(17.9±0.8)μg.mL-1(n=3),不引起溶血的发生;微乳与脂肪乳主要药动学参数t1/2α分别为(1.506±0.994)和(2.512±2.122)min,t1/2β分别为(42.221±43.878)和(49.095±42.521)min,V1分别为(1.947±1.17)和(3.546±3.836)L.kg-1,CL分别为(0.218±0.07)和(0.219±0.068)L.min-1.kg-1,AUC0～t分别为(17.916±6.772)和(16.968±5.395)mg.min.L-1,AUC0～∞分别为(20.488±7.729)和(...     

葛根素微乳的制备

目的:制备葛根素微乳口服给药系统(PUE-ME).方法:通过溶解度实验、处方配伍实验和伪三元相图的绘制,以乳化时间、色泽为指标,筛选油相、表面活性剂、助表面活性剂的最佳搭配和处方配比.结果:葛根素在微乳中的溶解度最高可达77.11 mg/mL.结论:所制备的PUE-ME对葛根素增溶效果显著,将为PUE的口服制剂的进一步开发提供依据.     

Development and evaluation of a microemulsion formulation for transdermal delivery of terbinafine

The aim of the present study is to develop and evaluate microemulsion formulations for Terbinafine (TB) with a view to enhance its permeability through the skin and provide release for 24 h. Various o/w microemulsions were prepared by the spontaneous emulsification method. Oleic acid was chosen as the oil phase, Caprylo caproyl macrogol-8- glyceride (Labrasol S) and purified diethylene glycol monoethyl ether (Transcutol P) were used as surfactant and cosurfactant, respectively, on the basis of solubility studies. Pseudoternary phase diagrams were constructed to obtain the concentration range of oil, surfactant, cosurfactant, and water for microemulsion formulation. The optimized microemulsion consisted of 2% w/w TB, 8% w/w oleic acid, 31% w/w labrasol S, 31% w/w transcutol P, and 30% w/w distilled water. Permeability parameters like Jss and Kp were found to be significantly higher for formulation F4 as compared to other formulations (P < 0.05). Microbiological studies of TB in microemulsion showed better anti-fungal activity against Candida albicans and Aspergillus flavus as compared to marketed product (P < 0.05).     

双嘧达莫微乳的制备及质量评价

目的:制备双嘧达莫水包油型微乳制剂,并对其稳定性及质量进行考察。方法:通过双嘧达莫在各溶媒中的溶解度初步确定处方组成,通过绘制伪三元相图对处方进行优化,考察优化处方的黏度、电导率、折光率、Zeta电位、粒径分布等理化性质,并对其稳定性进行测试。结果:在Km=3∶1时,伪三元相图形成的微乳区域最大,微乳平均粒径为59.7 nm,在高速离心、高温、强光下无分层,也无絮凝或药物析出。结论:双嘧达莫微乳制剂增加了药物的溶解度,制剂稳定,含量测定方法可靠,重复性好。     

尼莫地平微乳的制备及质量评价

目的:研究尼莫地平微乳的制备和质量评价.方法:考察尼莫地平在不同油相、乳化剂和助乳化剂中的平衡溶解度,并通过滴定法绘制伪三元相图,确定最优的Km值和处方,分别考察载药微乳的外观、稳定性、形态和粒径大小.用高效液相色谱法测定微乳中尼莫地平的包封率和载药量.结果:尼莫地平微乳为澄清或略带乳光的淡黄色液体,稳定,透射电镜下呈圆球形,分布均匀.平均粒径18.2 nm,呈Gauss分布.微乳经0.9%氯化钠注射液和5%葡萄糖注射液稀释50倍后,外观、pH值、载药量、粒径均无明显变化,高效液相色谱法测定包封率为97.62%,载药量为0.402 g·L-1.结论:微乳能提高尼莫地平的溶解度,微乳制剂质量稳定,易于制备.     

去甲斑蝥素微乳的制备和质量评价

目的 研究去甲斑蝥素微乳(NCID ME)的制备和质量评价方法。方法 通过滴定法绘制伪三元相图,根据相图优选处方,分别考察微乳制剂的稳定性、形态和对NCID的溶解性。用气相色谱法测定微乳中NCTD的含量。结果 NCTD ME稳定,透射电镜下呈圆球型,分布均匀。平均粒径45.1 nm,呈Gauss分布。NCTD在微乳中的溶解度为183.8 mg·ml-1。气相色谱测定回收率为99.54％,RSD=1.8％(n=5)。结论 微乳能显著提高NCTD溶解性,微乳制剂质量稳定,易于制备。检测方法可靠,重复性好。     

盐酸阿比朵尔微乳的制备及其质量评价

目的:研制阿比朵尔微乳并对其质量进行评价。方法:选用肉豆蔻酸异丙酯作为油相,蓖麻油聚氧乙烯醚-40、聚山梨酯-20和聚山梨酯80-司班20(质量比为49∶51)分别作为表面活性剂,乙醇、正丁醇和异丙醇作为助表面活性剂。再通过滴定法制备伪三元相图的基础上,根据相图优选处方,分别考察微乳制剂的稳定性、形态粒径;用高效液相色谱(HPLC)法测定微乳中阿比朵尔的含量。结果:以蓖麻油聚氧乙烯醚-40为表面活性剂和乙醇作为助表面活性剂形成微乳系统。阿比朵尔微乳稳定,透射电镜下呈圆球形,分布均匀,平均粒径为28.4nm,呈Gauss分布。用RP-HPLC法测定回收率为100.18%,RSD为0.51%(n=6)。结论:采用微乳作为药物载体制备口服阿比朵尔微乳,为开发阿比朵尔微乳新型口服制剂提供了依据;HPLC检测方法可靠,重复性好。     

Preparation and evaluation of ibuprofen-loaded microemulsion for improvement of oral bioavailability

The purpose of the current study was to improve the solubility of ibuprofen, a poorly water-soluble drug, in a microemulsion system that is suitable for oral administration. Microemulsion was prepared using different sorts of oils, surfactants, and co-surfactants. Pseudo-ternary phase diagrams were used to evaluate the microemulsion domain. The formulations were characterized by solubility of the drug in the vehicle, droplet size, and drug release. The optimal formulation consists of 17% Labrafil M 1944CS, 28% Cremophor RH40/Transcutol P (3:1, w/w), and 55% water, with a maximum solubility of ibuprofen up to 60.3?mg/ml. The mean droplet size of microemulsion was 57?nm. The pharmacokinetic study of microemulsion was performed in rats and compared with granule formulation. The microemulsion has significantly increased the C_max and area under the curve (AUC) compared to that of the granule (p?<?0.05). The relative bioavailability of ibuprofen in microemulsions was 1.9-fold higher than that of the granule. These results indicated that this novel microemulsion is a useful formulation for enhancing the oral bioavailability of ibuprofen.