浅谈固体自乳化药物传递系统固化技术

查阅最近的国内外文献，综述固体自乳化药物传递系统定义及特定，固体自乳化药物传递系统的各种固化技术。作为一种新型制剂，固体自乳化药物传递系统有着良好的开发前景。     

自乳化释药系统的研究进展

目的：介绍自乳化药物传递系统的研究进展。方法：根据国内、国外文献报道，进行全面综合、整理和归纳。结果：对自乳化药物传递系统的处方组成和质量评价作一介绍，重点对自乳化释药系统的应用现状与前景进行综述。结论：自乳化药物传递系统将有广阔的发展前景。     

自乳化药物传递系统的研究概况

目的:总结自乳化药物传递系统的研究概况.方法:对近期自乳化药物传递系统的形成机制、处方组成、体外质量评价及其在药剂学方面的应用进行介绍.结果与结论:自乳化药物传递系统对亲脂性和水难溶性的药物是一个非常有前景的新型载体系统.     

自乳化药物传递系统概述及研究进展

目的:介绍自乳化药物传递系统的研究情况及最新进展。方法:以"自乳化""药物传递系统"等的中、英文词汇为关键词,组合查询Elsevier数据库中1995-2013年相关文献并结合其他资料进行统计分析。结果与结论:共查询到文献37篇,其中有效文献30篇。通过对自乳化药物传递系统的定义及特点、结构及形成机制,处方组成、处方筛选及优化、制备方法、质量评价等方面的阐述,发现自乳化药物传递系统能增加难溶性药物的溶解分散能力和生物利用度;同时,固体自乳化药物传递系统已成为该领域的研究热点,如自乳化脂质混悬剂和自乳化复方制剂等。随着研究的不断深入,会有更多基于自乳化技术的新剂型出现。     

自乳化药物传递系统的应用与前景

自乳化药物传递系统对于亲脂性和难溶性药物是一个非常有希望的新型载体系统。本文综述了自乳化药物的传递系统的物化生物药剂学特性和其目前存在的问题,并预测了该药物传递系统的发展趋势。     

自乳化药物传递系统的研究进展

本文从自乳化释药系统组成、基本概念、自乳化机制、SEDDS在药物制剂中的应用及其在国内外的专利、SEDDS的处方设计等方面出发,总结自乳化药物传递系统的最新研究进展,并对自乳化传递系统的发展前景作了综述。     

自乳化药物传递系统的处方优化方法和应用

目的:综述自乳化药物传递系统的处方优化方法和应用。方法:查阅国内外相关文献进行归纳总结。结果:自乳化药物传递系统的处方优化方法有(伪)三元相图法、正交设计法、响应面优化法、D-优化法、定量构效关系法、高通量处方筛选法等。结论:在自乳化药物传递系统的研究中,可根据考察的因素和指标,选择合适的处方优化方法进行处方优化。     

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。     

自乳化药物传递系统

自乳化药物传递系统可改善药物的口服吸收,增加其生物利用度,是克服某些脂溶性或水难溶性药物制剂困难的一种极具潜力的方法。本文综述自乳化系统的组成、质量评价指标、影响其口服吸收的因素及其在给药实践中的应用。     

自乳化药物传递系统

自乳化药物传递系统可改善药物的口服吸收，增加其生物利用度，是克服某些脂溶性或水难溶性药物制剂困难的一种极具潜力的方法。本文综述自乳化系统的组成、质量评价指标、影响其口服吸收的因素及其在给药实践中的应用。     

Development of solid self-emulsifying drug delivery systems: preparation techniques and dosage forms

Approximately 40% of new chemical entities exhibit poor aqueous solubility and present a major challenge to modern drug delivery system, because of their low bioavailability. Self-emulsifying drug delivery systems (SEDDS) are usually used to improve the bioavailability of hydrophobic drugs. Conventional SEDDS, however, are mostly prepared in a liquid form, which can produce some disadvantages. Accordingly, solid SEDDS (S-SEDDS), prepared by solidification of liquid/semisolid self-emulsifying (SE) ingredients into powders, have gained popularity. This article gives an overview of the recent advances in the study of S-SEDDS, especially the related solidification techniques and the development of solid SE dosage forms. Finally, the existing problems and the possible future research directions in this field are pointed out.     

Enhanced oral bioavailability of dexibuprofen by a novel solid Self-emulsifying drug delivery system (SEDDS)

The main objective of this study was to prepare a solid form of lipid-based self-emulsifying drug delivery system (SEDDS) by spray drying liquid SEDDS with an inert solid carrier Aerosil 200 to improve the oral bioavailability of poorly water-soluble drug dexibuprofen. The liquid SEDDS was a system that consisted of dexibuprofen, Labrasol, Capryol 90 and Labrafil M 1944 CS. The particle size analysis revealed no difference in the z-average particle diameter of the reconstituted emulsion between liquid and solid SEDDS. The solid SEDDS was characterized by SEM, DSC and XRD studies. In vivo results of solid SEDDS and dexibuprofen powder in rats at the dose of 10 mg/kg showed that the initial plasma concentrations of drug in solid SEDDS were significantly higher than those of dexibuprofen powder (P < 0.05). The solid SEDDS gave significantly higher AUC and Cmax than did dexibuprofen powder (P < 0.05). In particular, the AUC of solid SEDDS was about twofold higher than that of dexibuprofen powder. Our results suggested that this solid SEDDS could be used as an effective oral solid dosage form to improve the bioavailability of poorly water-soluble drug dexibuprofen.     

Development and characterization of liquid and solid self-emulsifying drug delivery system of fexofenadine

Fexofenadine, the active metabolite of terfenadine, a well known and effective H1 receptor antagonist, is administered by the oral route. The objective of present investigation was to develop and characterize a liquid self-emulsifying drug delivery system (SEDDS) and a solid SEDDS by using bioenhancer excipients like Tween 80 and Labrasol which are known for their inhibiting action on CYP450 and P-glycoprotein pump. Solubility of fexofenadine was determined in various vehicles, including oils, surfactants and co-solvents. Various evaluation parameters (emulsification study, particle size, poly-dispersibility index, % drug release, etc.) were carried out to find out optimized liquid SEDDS formulation. Optimized liquid formulations were converted in solid SEDDS by simple and convenient physical adsorption technique. Solid SEDDS was characterized by X-ray diffraction (XRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and Fourier transport infra-red spectroscopy. The optimized liquid SEDDS formulation contained 29 % Captex 200P/Capmul MCM C8 EP as oil, 47 % Labrasol/Tween 80 as a surfactant and 24 % Ethanol as a co-solvent. The optimized liquid and solid SEDDS showed higher drug release than pure API powder. DSC and XRD results of solid SEDDS confirmed that the drug presented in the formulation was in an amorphous state. The prepared liquid SEDDS and solid SEDDS containing bio-enhancer excipients increased the in vitro dissolution rate of fexofenadine compared to pure drug and has potential to increase bioavailability by blocking Pgp efflux pump and CYP450 hepatic metabolism.     

Self-emulsifying drug delivery systems for improving oral absorption of ginkgo biloba extracts

Self-emulsifying drug delivery systems (SEDDS) are mixtures of oils, surfactants, and cosurfactants, which are emulsified in aqueous media under conditions of gentle stirring and digestive motility that would be encountered in the gastrointestinal tract. We found that SEDDS could efficiently improve oral absorption of the sparingly soluble drugs by rapid self-emulsification and subsequently dispersion in the absorption sites. Ginkgo biloba extract (GBE) has become a widely used herbal remedy for increasing cognitive function in elderly people. The main purpose of our work is to prepare SEDDS for improving oral absorption of GBE. Pseudoternary phase diagrams were constructed to identify the efficient self-emulsification region, and particle size distributions of resultant emulsions were determined. The optimized formulation for bioavailability assessment consisted of 45% Tween 80-Cremophor EL35 (1:1, w/w), 10% 1, 2-propanediol, and 45% ethyl oleate. The mean droplet size distribution of the optimized SEDDS was approximately 100 nm when diluted with 500-fold volume of the distilled water. The in vitro dissolution rates of the active components of GBE SEDDS form were significantly faster than those of the GBE tablets. After single oral administration of 800 mg GBE as SEDDS or tablets to fasted dogs, the relative bioavailability of SEDDS for bilabolide and ginkgolide A and B was 162.1, 154.6, and 155.8% compared with the reference tablets, respectively. Our results suggested the potential and promising use of SEDDS for the efficient delivery of the sparingly soluble drugs or traditional Chinese medicines, such as GBE by oral administration.     

靛玉红及其磷脂复合物和自乳化释药系统在犬体内的药动学

目的:考察靛玉红及其磷脂复合物和自乳化释药系统在犬体内的药动学过程。方法:采用三周期交叉试验设计法,取6条健康beagle犬随机分成3组,分别服用剂量为100mg的靛玉红片、靛玉红磷脂复合物和靛玉红自乳化释药系统,用高效液相色谱(HPLC)法测定靛玉红的血药浓度,利用3P97软件包和统计矩方法计算主要药动学参数和相对生物利用度。结果:以靛玉红片为对照,靛玉红磷脂复合物和自乳化释药系统的相对生物利用度分别为(157±s 10)%和(162±16)%。结论:磷脂复合物和自乳化释药系统有利于改善靛玉红口服生物利用度。     

酮洛芬自乳化制剂处方及化学稳定性研究

目的建立酮洛芬自乳化制剂处方 ,并考察其稳定性。方法通过溶解度实验和三元相图的建立 ,筛选酮洛芬自乳化制剂处方。用HPLC法测定处方经高低温循环和光照加速实验前后药物的含量 ,考察其化学稳定性。结果酮洛芬自乳化制剂处方中油相、表面活性剂和助表面活性剂分别为油酸乙酯、Tween 80和乙二醇单乙基醚 (Transcutol)。处方经高低温循环后酮洛芬平均含量由 99 8% (w)变为 99 0 % (w) ,光照 5d和 10d后 ,平均含量分别降为 85 7% (w )和 6 8 7%(w )。结论酮洛芬自乳化制剂处方比例为酮洛芬 油酸乙酯 Tween 80 Transcutol(w∶w∶w∶w =5 0∶4 0 0∶4 3 5 0∶11 5 )。制剂对热稳定 ,对光不稳定 ,需避光保存     

茴拉西坦自乳化给药系统与片剂的药代动力学及体内外相关性的研究

目的：研究茴拉西坦自乳化制剂和普通片剂的体内外相关关系;评价其大鼠口服给药的体内药代动力学。方法：通过测定自乳化制剂和普通片剂的体外溶出度考察其释药特性,采用RP-HPLC法测定活性代谢产物对氨基甲氧基丁酸的浓度血浆中,通过Wagner-Nelson法计算体内吸收分数（f）,研究两制剂的吸收分数（f）与体外累积溶出度（Q%）的相关性。结果：自乳化微乳体外15min的溶出度为（80±4）%,比片剂的溶出度（50%）明显提高;体内代谢产物的回收率为90%,日内日间精密度分别小于4%和6%,该方法灵敏度高、准确可靠。自乳化微乳的AUC0-∞为（11168±2395）ng·mL^-1·h,是普通片剂的3倍。自乳化微乳和片剂的MRT0-∞分别为（2.7±0.6）h和（1.7±0.5）h,具有统计学差异（P〈0.05）。体内外相关性结果表明,片剂的体内吸收与体外溶出度呈线性相关,线性方程的斜率为0.7765,截距为-2.9527;自乳化微乳的体内外相关性符合二次模型,其拟合系数为0.972。结论：茴拉西坦自乳化给药系统可显著提高药物体内的生物利用度。自乳化制剂处方中含有促吸收的复合表面活性剂和油相,其体外药物呈快速释放的特性,而体内自发与胃肠液形成o/w型微乳后可通过淋巴转运的吸收途径。     

Self-emulsifying drug delivery system and the applications in herbal drugs

Abstract

Herbal drugs have been used for thousands of years in the east and have had a recent resurgence in popularity among consumers in the west. However, most of herbal drug are poorly soluble and have hydrophobic properties and poor distribution, leading to reduced bioavailability and hence decreased treatment efficacy, requiring repeated administration or increased dose. In the past few decades, considerable attention has been focused on the development of self-emulsifying drug delivery system (SEDDS) for herbal drugs. SEDDS is isotropic and thermodynamically stable solutions consisting of oil, surfactant, co-surfactant and drug that can spontaneously form oil-in-water micro/nanoemulsion when mixed with water under gentle stirring. The formulation can be a viable alternative to classical formulations to take advantage of their lipophilic nature and to solve their problems of poor solubility, poor bioavailability, low oral absorption and instability. The mechanism of self-emulsification, solubility studies, construction of phase diagram, optimization and characterization of herbal drugs-loaded SEDDS formulation and in situ absorption evaluation of herbal drugs in rat intestine are presented in our article.     

Improved Intestinal Mucus Permeation of Vancomycin via Incorporation Into Nanocarrier Containing Papain-Palmitate

The aim of this study was to improve intestinal mucus permeation of a peptide antibiotic via incorporation into papain-palmitate–modified self-emulsifying drug delivery systems (SEDDS) as nanocarrier. Vancomycin as a peptide antibiotic was lipidized by hydrophobic ion pair formation using sodium bis-2-ethylhexyl-sulphosuccinate before incorporation in SEDDS comprising Capmul MCM, propylenglycol, and Kolliphor EL (2:1:2). As mucolytic agent, 0.5% papain-palmitate was introduced in SEDDS formulation containing the vancomycin-sodium bis-2-ethylhexyl-sulphosuccinate ion pair. The formulation was evaluated regarding droplet size, zeta potential, and cytotoxicity using Caco-2 cells previous to intestinal mucus permeation studies using Transwell diffusion and rotating tube method. The hydrophobic ion pair product yielded from surfactant to drug ratio of 3:1 provided a 25-fold increase in lipophilicity, drug payload in SEDDS of 5%, and log D_{SEDDS/release medium} of 2.2. The formulation exhibited a droplet size and zeta potential of 221.5 ± 14.8 nm and ?4.2 ± 0.8 mV, respectively. Cytotoxicity study showed that SEDDS formulations were not toxic. Introducing 0.5% papain-palmitate increased the mucus permeability of SEDDS 2.8-fold and 3.3-fold in Transwell diffusion and rotating tube studies, respectively. According to these results, papain decorated SEDDS might be a potential strategy to improve the mucus permeating properties of peptide antibiotics.     

Enhanced oral bioavailability of piperine by self-emulsifying drug delivery systems: in vitro,in vivo and in situ intestinal permeability studies

Abstract

The main purpose of this work was to develop and evaluate a self-emulsifying drug delivery system (SEDDS) of piperine to enhance its solubility and bioavailability. The formulation was optimized by solubility test and ternary phase diagrams. Then physiochemical properties and in vitro release of SEDDS were characterized. In vivo pharmacokinetics study and in situ single-pass intestinal perfusion were performed to investigate the effects of SEDDS on the bioavailability and intestinal absorption of piperine. The optimized formulation was composed of ethyl oleate, Tween 80 and Transcutol P (3:5.5:1.5, w/w), with the level of the piperine reached 2.5% (w/w). The in vitro dissolution rates of piperine SEDDS were significantly higher than the self-prepared capsules. In vivo pharmacokinetic study showed C_max1, C_max2 and area under the curve of piperine after oral administration of SEDDS in rats were 3.8-, 7.2- and 5.2-fold higher than the self-prepared capsules, respectively, and the relative bioavailability of SEDDS was 625.74%. The in situ intestinal absorption study revealed that the effective permeability and the effective absorption rate values of piperine for SEDDS were significantly improved comparing to solutions (p?<?0.01). So SEDDS formulation could improve the oral bioavailability and intestinal absorption of piperine effectively.