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 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).     

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。     

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.     

美洛昔康凝胶剂的制备及其经皮吸收研究

目的：制备美洛昔康凝胶剂，研究其经皮吸收过程。方法：采用双室渗透扩散装置，小鼠皮肤作为试验材料，进行体外渗透材料。结果：油酸，红桧油，Azone，桉叶油均能有效地促进美洛昔康的渗透，其中油酸的渗透系数和增渗倍数比其他促进剂大。结论：凝胶剂的最佳处方为：0．1％美洛昔康，2％油酸，卡波普／羟丙甲纤维素为2：1，凝胶剂中药物的渗透可用Higuchi方程来描述。     

Preparation and evaluation of flurbiprofen-loaded microemulsion for parenteral delivery.

The purpose of this study was to improve the solubility of flurbiprofen, a poorly water-soluble drug, in an oil-in-water (o/w) microemulsion that is suitable for parenteral administration. Microemulsions with varying ratios of oil to surfactant were prepared with ethyl oleate, Tween 20 and isotonic solution. The effect of formulation variables on the particle size of microemulsion and solubility of flurbiprofen in microemulsion system was investigated. The pharmacokinetic parameters of flurbiprofen after intravenous administration of flurbiprofen-loaded microemulsion were compared with those of a solution of the drug. The mean droplet diameter of microemulsion containing less than 1% (w/w) of flurbiprofen was below 100 nm. The maximum solubility of flurbiprofen in the microemulsion system was found to be 10 mg/ml. However, the mean droplet diameters of flurbiprofen-loaded o/w microemulsions tend to be increased at room temperature. The pharmacokinetic parameters of flurbiprofen after intravenous administration of flurbiprofen-loaded microemulsion to rats were not significantly different from those of flurbiprofen in phosphate-buffered saline solution. It can be concluded that microemulsions of flurbiprofen prepared with ethyl oleate and Tween 20 can be used as a parenteral drug carrier for this and other poorly water-soluble drugs, provided that physical stability can be properly addressed. Copyright     

Preparation and characterization of microemulsion formulations of nicotinic acid and its prodrugs for transdermal delivery

At pharmacological doses, nicotinic acid has a lipid-regulating effect and is in use clinically for that purpose. However, despite of all features, its utility is strongly limited by several disadvantages such as, extensive hepatic metabolism and flushing. Transdermal delivery of nicotinic acid may, therefore, be the solution to reducing side effects associated with oral administration, and to maintaining constant therapeutic blood levels for longer duration. The aim of this investigation was to develop a suitable formulation or select a suitable vehicle for the transdermal delivery of highly lipophilic prodrugs of nicotinic acid (dodecyl and myristyl nicotinate) designed to deliver nicotinic acid through skin without causing vasodilatation and flushing and optimizing its delivery to the blood stream. A microemulsion system and penetration enhancers have been attempted in this study. The microemulsion system was composed of isopropyl myristate (IPM), water and a 4:1 (w/w) mixture of Labrasol and Peceol where a pseudoternary phase diagram was constructed. Furthermore, the microemulsion formulations with different component ratios were characterized by determination of conductivity, pH, particle size, viscosity and refractive index. According to the particle size analysis, conductivity and viscosity measurements, the microemulsion formulations that formed were of oil-in-water type. The transdermal permeability of nicotinic acid and its prodrugs was evaluated in vitro using Franz diffusion cells fitted with mice skin and nicotinic acid concentration was analyzed by high performance liquid chromatography. A theoretical design of percutaneous penetration optimization in which prodrugs derivation and enhancer application are combined based on the skin diffusion model was experimentally verified. The selected formulations seemed promising for developing a transdermal drug delivery system of nicotinic acid from dodecyl nicotinate that would offer advantages like possible controlled drug release, reduced flushing, increased drug stability and ease of large-scale production.     

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.     

Formulation of microemulsion systems for transdermal delivery of aceclofenac

An ONW microemulsion system was developed to enhance the skin permeability of aceclofenac. Of the oils studied, Labrafil M 1944 CS was chosen as the oil phase of the microemulson, as it showed a good solubilizing capacity. Pseudo-ternary phase diagrams were constructed to obtain the concentration range of oil, surfactant, Cremophor ELP, and co-surfactant, ethanol, for micoemulsion formation. Eight different formulations with various values of oil of 6-30%, water of 0-80%, and the mixture of surfactant and co-surfactant (at the ratio of 2) of 14-70%. The in vitro transdermal permeability of aceclofenac from the microemulsions was evaluated using Franz diffusion cells mounted with rat skin. The level of aceclofenac permeated was analyzed by HPLC and the droplet size of the microemulsions was characterized using a Zetasizer Nano-ZS. Terpenes were added to the microemulsions at a level of 5%, and their effects on the skin permeation of aceclofenac were investigated. The mean diameters of the microemulsions ranged between approximately 10-100 nm, and the skin permeability of the aceclofenac incorporated into the microemulsion systems was 5-fold higher than that of the ethanol vehicle. Of the various terpenes added, limonene had the best enhancing ability. These results indicate that the microemulsion system studied is a promising tool for the percutaneous delivery of aceclofenac.     

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.     

氨甲环酸纳米乳膏的制备及体外透皮效果评价

目的设计制备氨甲环酸纳米乳膏(TA-NC),并观察其体外透皮效果。方法采用高压均质法制备氨甲环酸纳米乳,并进一步制得TA-NC,检测TA-NC粒径、微观结构及包封率。以裸鼠皮肤为模型,通过体外透皮吸收实验、离体皮肤组织滞留实验考察TA-NC的体外透皮效果;以尼罗红为荧光探针制备荧光标记TA-NC,共聚焦显微镜观察其促透进入真皮层的效果。并考察TA-NC的6个月加速稳定性。结果制备的TA-NC粒径为(109.9±7.4)nm,形态圆整,分布均匀;包封率为(90.13±2.90)%。体外透皮吸收实验中,TA-NC组给药6 h药物皮肤中的累积滞留量达饱和状态,24 h累积透过量达(163.9±7.4)μg·cm-2;TA水溶液组皮肤的滞留量在20μg·cm-2以下,24 h累积透过量为(15.9±0.8)μg·cm-2,组间差异非常显著(P<0.01)。共聚焦显微镜下,荧光素TA水溶液组仅表皮角质层有荧光,荧光标记的TA-NC经皮吸收后可透过角质层和表皮层到达真皮层,且TA-NC粒径越小透皮能力越强。6个月内TA-NC制剂外观性状、有关物质、含量、粒度等均未发生明显改变。结论 TA-NC制备简单,透皮效果显著,稳定性好。     

酮基布洛芬贴片的制备及体外渗透性研究

目的：观察环丙沙星治疗下呼吸道感染的疗效。方法：１００例患者（男性５２例,女性４８例,年龄（４５±８）ａ用药剂量为５００ｍｇ,每１２ｈ口服１次,疗程一般为７～２１ｄ。结果：临床总有效率为９２０％,细菌清除率为８７２％,对革兰氏阳性及阴性菌均有效,敏感菌百分率达８８５％,特别对铜绿假单胞菌感染也有较好的疗效。结论：环丙沙星治疗下呼吸道感染疗效满意,副作用少,是安全、方便、可靠的有效药物。     

Novel sugar esters proniosomes for transdermal delivery of vinpocetine: Preclinical and clinical studies

Vinpocetine (Vin) existing oral formulations suffer poor bioavailability (∼7%) since Vin undergoes a marked first-pass effect (∼75%) and its absorption is dissolution rate-limited. In this study, a novel sustained release proniosomal system was designed using sugar esters (SEs) as non-ionic surfactants in which proniosomes were converted to niosomes upon skin water hydration following topical application under occlusive conditions. Different in vitro aspects (encapsulation efficiency, vesicle size and shape, effect of occlusion, in vitro release, skin permeation and stability) were studied leading to an optimized formula that was assessed clinically for transdermal pharmacokinetics and skin irritation.All formulae exhibited high entrapment efficiencies, regardless of the surfactant HLB. Vesicle size analysis showed that all vesicles were in the range from 0.63 μm to 2.52 μm which favored efficient transdermal delivery. The extent of drug permeation through the skin from the optimized formula - containing laurate SE with shorter fatty acid chain length and high HLB - was quite high (91%) after 48 h under occlusive conditions. The extent of absorption of Vin from proniosomes was larger when compared to the oral tablet with a relative bioavailability (F_rel) of 206%. Histopathological evaluation revealed only moderate skin irritation when using SEs compared to skin inflammation when using Tween 80. Sugar esters proniosomes may be a promising carrier for vinpocetine, especially due to their simple scaling up and their ability to control drug release.     

Enhancement of transdermal delivery of theophylline using microemulsion vehicle

A microemulsion vehicle had been studied as a possible matrix for transdermal delivery of theophylline. The existence of microemulsion regions were investigated in pseudo-ternary phase diagrams, and various microemulsion formulations were prepared using oleic acid, Cremophor RH40/Labrasol (1:2) and water. The optimal formulation of the microemulsion was evaluated in vitro using Franz diffusion cells. The droplet size of microemulsion was characterized by photo correlation spectroscopy. Pharmacokinetic study in vivo was conducted using rabbits, and the results indicated that AUC(0-->infinity) of transdermal administration was 1.65-fold higher than that of oral solution administration. These studies showed that microemulsion system of theophylline might be promising vehicles for the transdermal delivery of theophylline.     

萘普生微乳经皮给药系统的处方前研究

目的:测定萘普生的表观溶解度和油水分配系数.研究溶解度、促渗剂、接受液对萘普生体外经皮渗透性能的影响.方法:采用高效液相色谱法(HPLC)测定萘普生在水、不同pH缓冲液、各种油相和表面活性剂中的溶解度.通过摇瓶法测定萘普生的表观油水分配系数.以累积渗透量、稳态渗透速率常数和渗透系数为评价指标研究5种促渗剂和5种接受液对萘普生体外经皮渗透行为的影响.结果:32℃时,萘普生在水中的平衡溶解度为25.7 mg·L-1,在各种油相和表面活性剂中的溶解度约是水中的200～4 000倍.萘普生在正辛醇/水体系中的表观油水分配系数为2.5(logP);在正辛醇/缓冲液体系中的表观油水分配系数随pH值的升高而减小.促渗剂的促渗效果不明显,有的还会抑制渗透;萘普生在以20%丙二醇-生理氯化钠溶液、pH 7.4缓冲液、20%乙醇-pH 7.4缓冲液、20%聚乙二醇400-pH 7.4缓冲液作为接受液时,均有良好的渗透效果,10 h累积透过量最小可达2.08 mg.结论:萘普生是一种优良的经皮给药模型药物,开发其经皮给药微乳制剂有望提高疗效、减少毒副作用.微乳可选择将萘普生溶解在油或表面活性剂中的方法制备,pH 7.4的缓冲液可作为其透皮制剂的接受液.     

遗传算法在经皮给药微乳载体处方优化中的应用

以萘普生为模型药物，用遗传算法优化经皮给药微乳载体的处方。用伪三元相图法确定由Tween 80、IPM、乙醇和水组成的微乳区域。用3因素3水平的中心设计法制备载药量为1.12%的萘普生模型微乳，并进行离体兔皮的体外渗透实验。以稳态渗透速率的二次回归模型为目标函数，用遗传算法对中心设计结果进行优化，筛选出具有最大透皮速率的萘普生微乳载体处方。所得优化处方的组成为：21.41% Tween 80、15.17%乙醇、4.14% IPM和59.28%水，预计的稳态渗透速率为183.57 μg·cm^-2·h^-1。回代试验表明，以优化处方制备的萘普生微乳，其稳态渗透速率的平均值为189.43 μg·cm^-2·h^-1，高于预测值。结果表明，用遗传算法筛选微乳经皮给药载体处方，方法可行，结果合理、可靠。     

己酮可可碱巴布剂的研制及质量评价

目的制备己酮可可碱巴布剂并按照《中华人民共和国药典》(2 0 0 0版 )的有关规定对其进行体外质量评价。方法通过正交实验确定己酮可可碱巴布剂的优化处方 ,利用Franz扩散池研究己酮可可碱的体外经皮渗透性 ,用HPLC法测定药物的经皮渗透量。结果己酮可可碱巴布剂经皮行为呈零级模式 ,2 4h累积渗透量为 1 98mg·cm-2 ,质量考察结果表明各项指标均符合要求 ;5 %NMP的增渗倍数最大 ,为 2 61。结论己酮可可碱巴布剂质量可控 ,刺激性小 ,是一种安全、有效的透皮给药系统     

长春西汀自微乳化给药系统的制备与体外评价

［摘要］目的：制备长春西汀自微乳化给药系统,并对其体外释药及初步稳定性进行了评价。方法：通过溶解度实验、相分离实验以及三元相图的研究筛选了长春西汀自微乳化处方;并对制剂进行了粒径分布、溶出度及初步稳定性的考察。结果：长春西汀自微乳处方组成：Solutol HS 15（A）为表面活性剂;Transcutol P（B）为辅助表面活性剂;Ethyl Oleate（C）为油相。所得处方的自微乳化时间<1min,粒径<100nm。体外释放实验表明自微乳化制剂受溶出介质pH值影响小,在不同pH值非依赖型介质中均能快速完全释放药物。结论：所制备的长春西汀自微乳化制剂能够显著提高难溶性药物的溶解度,为体内研究提供实验依据。     

Synthesis and evaluation of esmolol prodrugs for transdermal delivery

Esmolol hydrochloride, an important anti-hypertensive and anti-arrhythmic agent, is administered as intravenous infusion only. The objective of the present work is to screen the feasibility of this drug for transdermal delivery. To enhance the lipophilicity, a pro-drug approach was adopted. Four pro-drugs, esmolol acetate, propionate, butyrate, and valerate, were synthesized and characterized by IR, NMR, Mass spectroscopy, and elemental analysis. Physicochemical parameters were ascertained and in vitro skin permeability study was carried out using excised porcine skin. Drug and pro-drugs were assessed for anti-hypertensive effect on male Sprague Dawley rats and data was statistically analyzed by one-way ANOVA. The results indicate that esters had much higher lipophilicity (p?<?0.001) than the parent drug. All the esters had recorded significantly higher (p?<?0.001) skin permeability than the parent moiety, with esmolol valerate showing the highest steady state flux (1.899?±?0.035?µmol/cm²/h). Esters showed greater reduction of blood pressure than the parent drug, with esmolol propionate showing the highest efficacy. The findings suggest that esterification can be a promising tool for enhancing the skin permeability of esmolol, which is an essential requirement for transdermal development.     

长春西汀透皮贴剂的研制及体外释药机理的探讨

目的:制备长春西汀透皮贴剂,研究其体外释药机理.方法:在单层贴剂优化处方的基础上制备了单层、双层和三层贴剂,比较不同类型贴剂经不同皮肤的体外渗透速率,对三层贴剂进行了质量考察并研究了其释药机理.结果:三层贴剂和双层贴剂的经皮渗透量大于单层贴剂.去除角质层的皮肤对药物经皮渗透的屏障作用明显小于完整皮肤. 结论:长春西汀贴剂质量可控,刺激性小,药物经皮吸收的主要屏障为角质层,在经皮渗透中有较微弱的储库效应,其渗透行为主要是零级释药模式.