固体自微乳药物递送系统的研究进展

作为一种新型的药物递送系统,固体自微乳药物递送系统可以显著提高水难溶性药物的口服生物利用度,且具有液态自微乳和固体制剂二者的优势。通过设计不同的辅料处方和包衣技术,可以控制药物释放使其具有靶向性,来达到不同的给药目的。固体自微乳药物递送系统的应用前景广阔,具有研究意义。本文对固体自微乳载体、固化技术、固体自微乳新制剂的应用进行了总结归纳,为提高水难溶性药物释放的固体自微乳化技术的研究提供了参考。     

固体自微乳载体、固体化方法及稳定性研究进展

目的：对国内外近年来固体自微乳的载体、固体化方法及稳定性的研究进展进行综述,为该剂型的进一步研究和开发提供参考。方法：搜集国内外相关文献进行综合分析。结果：新型的载体材料和新的固体化方法可进一步提高固体自微乳的自乳化性能、药物的分散度,提高难溶性药物的溶出度和生物利用度,还可以改善药物的稳定性。结论：固体自微乳制剂具有微乳和固体制剂的双重优势,是非常具有研发前景的新型固体制剂,随着新型载体材料和固体化方法的开发,该剂型将得到广泛的应用。     

固体自（微）乳化释药系统的研究进展

目的：了解固体自（微）乳化释药系统的最新进展。方法：查阅国内外文献,对固体自（微）乳化释药系统的组成、固化技术及近年来固体自（微）乳化制剂的应用新进展进行概述。结果与结论：固体自（微）乳化释药系统能够显著促进难溶性药物的溶解和吸收,提高药物的生物利用度,是一种较理想的药物载体。但是对固体自（微）乳化制剂的研究还不够透彻,尚存在不少亟待解决的问题,如新型固体载体研究、固体载体筛选方法以及其对药物体内外性质的影响、体内外相关性的研究、制剂的产业化等。     

难溶性药物的制剂增溶技术及应用

目的：综述难溶性药物增溶和提高生物利用度的制剂技术及应用。方法：查阅国内外相关文献进行总结、归纳。结果：难溶性药物随着制剂技术的改进及新剂型的应用,可通过环糊精包合或复合、固体分散体、微粉化、加增溶剂或助溶剂、成盐处理等多种途径来提高药物的溶出速率和生物利用度。结论：随着药学领域中新制剂技术的发展、新材料的应用,难溶性药物的吸收差、生物利用度低这一限制已逐渐被克服,难溶性药物也可获得较好的吸收和生物利用度。     

难溶性西药制剂中自微乳化释药的应用研究

自微乳化释药系统是由油相、表面活性剂、助表面活性剂和药物组成的澄清、均一的液体或者固体制剂,是一种脂质给药系统。目前,很多药物在生物体内溶解度比较小,因此,如何增加药物的溶解度,提高生物利用度是西药制剂中的一大难题。本文对自微乳化释药系统的作用机制、处方研究以及在难溶性西药制剂中的应用作一综述。     

固体自乳化药物传递系统的研究概况

综述固体自乳化药物传递系统的定义与特点、处方组分、制备工艺、药物体外释放和体内吸收的影响因素及质量评价指标。固体自乳化药物传递系统为一种新型制剂，可以显著提高难溶性药物的口服生物利用度，还可以通过添加各种固体辅料或采用包衣技术制备缓控释产品。     

难溶性药物增溶研究进展

如何增加难溶性药物的溶解度,改善其生物利用度,一直是药剂学研究的重要内容。该文就近年来应用广泛的纳米混悬剂、渗透泵、自微乳化技术、固体分散体、固体脂质纳米粒、液固压缩技术等一些新方法新技术在增加难溶性药物溶解度及改善生物利用度方面的应用进行综述。     

自微乳化释药系统与液固压缩技术在难溶性中药制剂中的联合应用

药物的难溶性严重影响药物的生物利用度,也严重影响药物制成各类制剂。如何增加中药难溶性成分的溶解度,改善其生物利用度,一直是药剂学研究的重要内容。对于难溶性药物来说,药物只有处于溶解状态下,才能表现出较好的溶出和生物利用度。自微乳化释药系统和液固压缩技术均有很好的增溶作用,而且液固压缩技术使药物以无定形或分子状态给药,两者联合应用,可以显著提高药物的溶出度和生物利用度,为中药增溶领域提供一种新的思路与方法。     

自乳化释药系统与液固压缩技术联合开发难溶性药物新剂型的进展

提高难溶性药物溶解度,改善难溶性口服药物的生物利用度,一直是药剂学的热点和难点。本文旨在通过对自乳化释药系统和液固压缩技术的介绍,并阐述2种技术联合开发难溶性药物新剂型的优势,说明固体自乳化释药系统可以作为液体自乳化释药系统的提高或者替代,其具有降低生产成本,简化工业生产,提高稳定性与患者耐受性等方面的优势。     

自微乳化释药系统在药物制剂中的应用

很多新活性药物在生物体内溶解度很小,如何增加药物溶解度,提高其生物利用度是药物制剂工作中的一大难题.本文介绍了自微乳化释药系统的基本概述,并对其在难溶性西药制剂中的应用进行综述.     

微粉硅胶对固体自微乳化给药系统小肠吸收的影响

固体载体对固体自微乳化给药系统(solid self-microemulsifying drug delivery systems,S-SMEDDS)的体内外性质有重要影响。本文探讨微粉硅胶对S-SMEDDS药物吸收的影响,为选择适宜固体载体提供依据。通过研究微粉硅胶对小肠脂解和S-SMEDDS体外释放的影响,并采用新型体外脂解-吸收模型研究微粉硅胶对S-SMEDDS离体小肠吸收的影响。结果发现微粉硅胶既能提高脂解速率,增加脂解后水性分散相中药物分配,促进药物吸收;又会延缓S-SMEDDS体外释药,影响药物的吸收速度;最终导致对S-SMEDDS的离体小肠吸收没有显著性影响。而且微粉硅胶对脂解和释药的影响都与其用量有关,这提示微粉硅胶适合作为S-SMEDDS的固体载体,其用量需要进一步筛选优化。     

A novel nanomatrix system consisted of colloidal silica and pH-sensitive polymethylacrylate improves the oral bioavailability of fenofibrate

A novel solid particle system with a nanomatrix structure and without surfactant for the oral delivery of insoluble drugs was prepared. This used a combination of pH-sensitive polymethylacrylate and nano-porous silica, in order to improve the drug absorption using only pharmaceutical excipients and a relative simple process. The in vitro drug dissolution and in vivo oral bioavailability of this formulation, using fenofibrate as the model drug, were compared with other reference formulations such as a suspension, micronized formulation or self microemulsion drug delivery system (SMEDDS). The supersaturation stabilizing effect of different polymers was evaluated and the physicochemical characterization of the optimal formulation was conducted by SEM, TEM, surface area analysis, DSC, and XRD. The optimized formulation prepared with polymethylacrylate (Eudragit®L100-55) and silica (Sylysia®350) markedly improved the drug dissolution compared with other reference preparations and displayed a comparative oral bioavailability to the SMEDDS. Fenofibrate existed in a molecular or amorphous state in the nanomatrix, and this state was maintained for up to 1 year, without obvious changes in drug release and absorption. In conclusion, the nanomatrix formulation described here is a promising system to enhance the oral bioavailability of water-insoluble drugs.     

Enhanced intestinal lymphatic absorption of saquinavir through supersaturated self-microemulsifying drug delivery systems

The therapeutic potential of saquinavir, a specific inhibitor of human immunodeficiency virus (HIV)-1 and HIV-2 protease enzymes, has been largely limited because of a low solubility and consequnt low bioavailability. Thus, we aimed to design a supersaturated self-microemulsifying drug delivery system (S-SMEDDS) that can maintain a high concentration of saquinavir in gastro-intestinal fluid thorugh inhibiting the drug precipitation to enhance the lymphatic transport of saquinavir and to increase the bioavailability of saquinavir considerably. Solubilizing capacity of different oils, surfactants, and cosurfactants for saquinavir was evaluated to select optimal ingredients for preparation of SMEDDS. Through the construction of pseudo-ternary phase diagram, SMEDDS formulations were established. A polymer as a precipitation inhibitor was selected based on its viscosity and drug precipitation inhibiting capacity. The S-SMEDDS and SMEDDS designed were administered at an equal dose to rats. At predetermined time points, levels of saquinavir in lymph collected from the rats were assessed. SMEDDS prepared presented a proper self-microemulsification efficiency and dispersion stability. The S-SMEDDS fabricated using the SMEDDS and hydroxypropyl methyl cellulose 2910 as a precipitation inhibitor exhibited a signficantly enhanced solubilizing capacity for saquinavir. The drug concentration in a simulated intestinal fluid evaluated with the S-SMEDDS was also maintained at higher levels for prolonged time than that examined with the SMEDDS. The S-SMEDDS showed a considerably enhanced lymphatic absoprtion of saquinavir in rats compared to the SMEDDS. Therefore, the S-SMEDDS would be usefully exploited to enhance the lymphatic absorption of hydrophobic drugs that need to be targeted to the lymphatic system.     

微乳在注射给药系统中的应用研究进展*

微乳是热力学稳定的液-液分散体系,粒径在10~100 nm之间,它作为新型给药系统,由于其具有增溶、缓释、提高生物利用度等显著优点,在口服、经皮、注射给药方面均有广泛应用研究。更由于其低黏度,可直接注射,以及靶向的特性在注射给药方面显示出独特的优势。现对微乳在注射给药系统中的应用研究进展进行综述。     

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。     

Preparation and pharmacokinetics evaluation of oral self-emulsifying system for poorly water-soluble drug Lornoxicam

Abstract

The present work was performed aiming to develop a new solid self-emulsifying system (SMEDDS) for poorly water-soluble drug Lornoxicam and evaluate the bioavailability in Wister rats by oral gavage. Liquid SMEDDS of Lornoxicam was formulated with Labrafil M 1944 CS as oil phase, Kolliphor HS 15 as a surfactant and Transcutol HP as a cosurfactant after screening various vehicles. The microemulsion system selected from the phase diagram and optimized by central composite design (CCD) response surface method was transformed into solid-SMEDDS (S-SMEDDS) by lyophilization using sucrose as cryoprotectant. The formulations were further characterized by the particle size, poly dispersity index (PDI), self-emulsifying time, zeta potential, transmission electron microscope (TEM), differential scanning calorimeter (DSC), in vitro drug release and in vivo pharmacokinetics. Results of DSC studies confirmed that the drug was incorporated in the S-SMEDDS. The in vitro drug release from Lornoxicam SMEDDS was found to be greatly higher in comparison with that from the commercial tablets. It was indicated that SMEDDS might be effective in reducing the effect of pH variability of Lornoxicam and improving the release performance of Lornoxicam. HPLC system was applied to study the concentration of Lornoxicam in the plasma of the Wister rats after oral administration of Lornoxicam SMEDDS and Lornoxicam commercial tablets. The pharmacokinetics parameters of the rats were C_max 1065.91?±?224.90 and 1855.22?±?748.25?ngmL^?1, T_max were 2.5?±?0.4?h and 1.8?±?0.5?h, and AUC_0～t were 5316.35?±?323.62 and 7758.07?±?241.57?ngmL^?1?h, respectively. Calculated by AUC_0～∞, the relative bioavailability of Lornoxicam S-SMEDDS was 151.69?±?15.32%. It suggested that this S-SMEDDS could be used as a successful oral solid dosage form to improve the solubility and bioavailability of poorly water-soluble drug Lornoxicam as well.     

Increased dissolution rate and oral bioavailability of hydrophobic drug glyburide tablets produced using supercritical CO2 silica dispersion technology

The aim of this study was to design a silica-supported solid dispersion of a water-insoluble drug, glyburide, to increase its dissolution rate and oral absorption using supercritical fluid (SCF) technology. DSC and PXRD results indicated that the encapsulated drug in the optimal solid dispersion was in an amorphous state and the product was stable for 6 months. Glyburide was adsorbed onto the porous silica, as confirmed by the SEM images and BET analysis. Furthermore, FT-IR spectroscopy confirmed that there was no change in the chemical structure of glyburide after the application of SCF. The glyburide silica-based dispersion could also be compressed into tablet form. In vitro drug release analysis of the silica solid dispersion tablets demonstrated faster release of glyburide compared with the commercial micronized tablet. In an in vivo test, the AUC of the tablets composed of the new glyburide silica-based solid dispersion was 2.01 times greater than that of the commercial micronized glyburide tablets. In conclusion, SCF technology presents a promising approach to prepare silica-based solid dispersions of hydrophobic drugs because of its ability to increase their release and oral bioavailability.     

Systematic development of design of experiments (DoE) optimised self-microemulsifying drug delivery system of Zotepine

The aim of present investigation is to improve dissolution rate of poor soluble drug Zotepine by a self-microemulsifying drug delivery system (SMEDDS). Ternary phase diagram with oil (Oleic acid), surfactant (Tween 80) and co-surfactant (PEG 400) at apex were used to identify the efficient self-microemulsifying region. Box–Behnken design was implemented to study the influence of independent variables. Principal Component Analysis was used for scrutinising critical variables. The liquid SMEDDS were characterised for macroscopic evaluation, % Transmission, emulsification time and in vitro drug release studies. Optimised formulation OL1 was converted in to S-SMEDDS by using Aerosil^® 200 as an adsorbent in the ratio of 3:1. The S-SMEDDS was characterised by SEM, DSC, globule size (152.1?nm), zeta-potential (?28.1?mV), % transmission study (98.75%), in vitro release (86.57%) at 30?min. The optimised solid SMEDDS formulation showed faster drug release properties as compared to conventional tablet of Zotepine.