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.     

纳米药物载体在经皮给药系统中应用的研究进展

目的介绍纳米药物载体在经皮给药系统中的应用。方法查阅国内外文献共31篇,从纳米药物载体在经皮给药系统中的应用及各自的优势和不足等方面进行综述。结果纳米药物载体具有提高药物的化学稳定性、促进药物经皮吸收、控制药物释放以及定位给药等优点,在药物的经皮吸收方面具有广阔应用前景。结论纳米药物载体为药物的经皮通透提供了新的途径和方法,但是其安全性和有效性仍需进一步研究。     

药物剂型和药物传输系统的发展综述

近年来,现代药剂学发展迅速,新剂型和药物传输系统展现了广阔的发展前景。发展新剂型和新给药系统可以获得短期内成效,使药品差异化,提高制药企业研发及产业化水平。在有限的资源分配下,我国唯有发展制剂创新才能缩小同发达国家的差距。本文就现代药剂学的发展进行综述,重点探讨剂型和给药系统的相关理论和应用,介绍了药剂学的最新研究进展,并总结未来发展可能遇到的挑战和机遇。     

国内外药物释放系统研究的文献计量学分析

利用互联网Medline数据库、清华全文数据库、欧洲专利数据库和中国知识产权局专利数据库,应用统计和情报分析的方法,对国内外近年来发表的有关药物释放系统(DDS)主题文献的论文进行文献数量、年代及研究内容的统计分析,同时对国内外药物制剂专利公布情况进行资料统计,对比分析国内外DDS的研究领域、研究重点变化及发展趋势,探讨我国未来DDS的研究重点与发展前景。     

我国药物释放系统发展对策与建议

在综合分析药物释放系统发展趋势、我国药物释放系统发展的实际水平及存在问题的基础上,提出我国药物释放系统发展的对策与建议。     

Recent progress in drug delivery systems for anticancer agents

Recent progress in understanding the molecular basis of cancer brought out new materials such as oligonucleotides, genes, peptides and proteins as a source of new anticancer agents. Due to their macromolecular properties, however, new strategies of delivery for them are required to achieve their full therapeutic efficacy in clinical setting. Development of improved dosage forms of currently marketed anticancer drugs can also enhance their therapeutic values. Currently developed delivery systems for anticancer agents include colloidal systems (liposomes, emulsions, nanoparticles and micelles), polymer implants and polymer conjugates. These delivery systems have been able to provide enhanced therapeutic activity and reduced toxicity of anticancer agents mainly by altering their pharmacokinetics and biodistribution. Furthermore, the identification of cell-specific receptor/antigens on cancer cells have brought the development of ligand- or antibody-bearing delivery systems which can be targeted to cancer cells by specific binding to receptors or antigens. They have exhibited specific and selective delivery of anticancer agents to cancer. As a consequence of extensive research, clinical development of anticancer agents utilizing various delivery systems is undergoing worldwide. New technologies and multidisciplinary expertise to develop advanced drug delivery systems, applicable to a wide range of anticancer agents, may eventually lead to an effective cancer therapy in the future.     

Pharmacokinetics of cefazolin administered as a new drug delivery system in healthy volunteers

A study was made of the pharmacokinetic behaviour in plasma and urine of cefazolin in seven healthy volunteers following parenteral administration of sodium cefazolin (1250 mg) and a sustained release formulation containing sodium cefazolin: cefazolin-dibenzylamine (1:4) at a total dose of 1250 mg, both formulations being administered over 1 week by the i.m. route. Cefazolin concentrations in plasma and urine were determined by a HPLC technique. Kinetic analysis of the experimental results was performed using an open single-compartment kinetic model and a sustained release model for the drug administered as standard formulation and the sustained release formulation, respectively. The results obtained point to significant variations in the pharmacokinetic profile of the drug when administered in the DDS. The time of cefazolin at levels greater than 1 microgram ml-1 was 16.03 +/- 2.51 and 47.76 +/- 14.18 h-1 after administration of the standard formulation and the DDS, respectively. The urinary excretion rate curves also show the existence of sustained drug levels in the urine following administration of the DDS. The renal clearance of the drug did not show statistically significant differences between the two formulations administered. The process of release of cefazolin from the cefazolin-dibenzylamine complex proved to be a first order kinetic process. The release constant of the antibiotic was calculated according to three different methods: the Wagner-Nelson method; the statistical moments method; and the fitting of the plasma levels curves to a compartmental model considering release and absorption. The values obtained for this constant ranges from 0.026 +/- 0.02 h-1 calculated with the method of statistical moments to 0.094 +/- 0.03 h-1 as calculated by the equation derived for the plasma fitting of cefazolin administered as DDS.     

Preparation and evaluation of a sustained morphine delivery system in rats

A new drug delivery system to induce physical dependence to morphine in rats is described. The device consists of a silicone polymer containing a water soluble "carrier" material, sodium alginate, which swells on contact with moisture to release the drug. The silicone or silastic pellets formulated to contain morphine sulfate are very easily prepared and the advantages over existing methods to induce physical dependence to morphine are discussed. In addition, a comparison of the percent of drug released and withdrawal intensities in rats was made with a silastic-morphine sulfate pellet, silastic-morphine base pellet and a microcrystalline cellulose-morphine base pellet.     

Lipid nanocapsules: Ready-to-use nanovectors for the aerosol delivery of paclitaxel

Aerosol drug delivery permits the development of dose-intensification strategies in severe, malignant lung diseases. The aim of the study was to demonstrate that the encapsulation of paclitaxel in lipid nanocapsules (LNCs), a novel drug nanocarrier for lipophilic components, allows one to provide pulmonary drug delivery of paclitaxel by nebulisation, thereby allowing preclinical and clinical studies. LNC dispersions are made into aerosols with commercial nebulisers. The structure, drug payload and cytotoxicity of nebulised LNCs were compared to fresh LNCs. The results demonstrated that LNC dispersions could be made into aerosols by using mesh nebulisers without altering the LNC structure. Only eFlow^® rapid-produced aerosols are compatible with human use: the mean duration to nebulise 3 ml of LNC dispersion is less than 9 min, with an aerosol mass median aerodynamic diameter equal to 2.7 ± 0.1 μm and a fine-particle fraction (between 1.0 and 5.0 μm) of 81.5 ± 3.1%. No modifications of drug payload or cytotoxicity effects of paclitaxel-loaded LNC (PTX–LNC) were observed. In order to carry out preclinical studies, a scaled-up LNC formulation protocol was used. Chemical parameters, such as acidity and osmolarity, were optimised, and a storage procedure for PTX–LNC batches was set-up. Animal studies are now needed to determine the tolerance and therapeutic potential of LNC dispersion aerosols.     

药物载体用于递送肿瘤坏死因子相关凋亡诱导配体的研究进展

肿瘤坏死因子相关凋亡诱导配体（Tumor necrosis factor-related apoptosis-inducing ligand,TRAIL）是肿瘤坏死因子家族的成员之一,可与肿瘤细胞膜表面过度表达的死亡受体4或5结合,特异性诱导肿瘤细胞凋亡,且对正常细胞无明显影响,因此被认为是临床最有发展前景的蛋白药物之一。然而,由于肿瘤坏死因子相关凋亡诱导配体存在体内稳定性差和生物利用度低等缺点,限制了其在临床中的应用。运用药物载体对肿瘤坏死因子相关凋亡诱导配体进行递送,成为目前解决此弊端的有效策略。本综述简要介绍了近年来药物载体在肿瘤坏死因子相关凋亡诱导配体递送方面的研究进展。     

Ultrasonic gene and drug delivery to the cardiovascular system

Ultrasound targeted microbubble destruction has evolved as a promising tool for organ specific gene and drug delivery. This technique has initially been developed as a method in myocardial contrast echocardiography, destroying intramyocardial microbubbles to characterize refill kinetics. When loading similar microbubbles with a bioactive substance, ultrasonic destruction of microbubbles may release the transported substance in the targeted organ. Furthermore, high amplitude oscillations of microbubbles lead to increased capillary and cell membrane permeability, thus facilitating tissue and cell penetration of the released substance. While this technique has been successfully used in many organs, its application in the cardiovascular system has dominated so far. Drug delivery using microbubbles has played a minor role in the cardiovascular system. In contrast, gene transfer has been successfully achieved in many studies. Both viral and non-viral vectors were used for loading on microbubbles. This review article will give an overview on studies that have applied ultrasound targeted microbubble destruction to deliver substances in the heart and blood vessels. It will show potential therapeutic targets, especially for gene therapy, describe feasible substances that can be loaded on microbubbles, and critically discuss prospects and limitations of this technique.     

Solid super saturated self-nanoemulsifying drug delivery system (sat-SNEDDS) as a promising alternative to conventional SNEDDS for improvement rosuvastatin calcium oral bioavailability

ABSTRACT

Objective: This study aims to illustrate the applicability of solid supersaturated self-nanoemulsifying drug delivery system (sat-SNEDDS) for the improvement of rosuvastatin calcium (RC) oral bioavailability.

Methods: Different sat-SNEDDS were prepared by incorporating different ratios of RC into SNEDDS using tween80/PEG400 (77.2%) as surfactant/cosurfactant mixture and garlic /olive oil (22.8%) as oil phase. The prepared systems were characterized viz; size, zeta potential, TEM and stability. Various hydrophilic and hydrophobic carriers were employed to solidify the optimized RC sat-SNEDDS. The influence of the carrier was investigated by SEM, XRPD, DSC, flow properties, in vitro precipitation, drug release and oral bioavailability study.

Results: The adsorption of the stable positively charged nanocarrier RC sat-SNEDDS onto solid carriers provided free flowing amorphous powder. The carrier could amend the morphological architecture and in vitro release of the RC solid sat-SNEDDS. Hydrophobic carriers as microcrystalline cellulose 102 (MCC) showed superior physical characters and higher dissolution rate over hydrophilic carriers as maltodextrin with respective T_100% 30 min and 45 min. The rapid spontaneous emulsification, the positively nanosized MCC-sat-SNEDDS improved oral bioavailability of RC by 2.1-fold over commercial tablets.

Conclusion: Solid MCC-sat-SNEDDS combined dual benefits of sat-SNEDDS and solid dosage form was successfully optimized to improve RC oral bioavailability.     

Iontophoresis: a potential emergence of a transdermal drug delivery system

The delivery of drugs into systemic circulation via skin has generated much attention during the last decade. Transdermal therapeutic systems propound controlled release of active ingredients through the skin and into the systemic circulation in a predictive manner. Drugs administered through these systems escape first-pass metabolism and maintain a steady state scenario similar to a continuous intravenous infusion for up to several days. However, the excellent impervious nature of the skin offers the greatest challenge for successful delivery of drug molecules by utilizing the concepts of iontophoresis. The present review deals with the principles and the recent innovations in the field of iontophoretic drug delivery system together with factors affecting the system. This delivery system utilizes electric current as a driving force for permeation of ionic and non-ionic medications. The rationale behind using this technique is to reversibly alter the barrier properties of skin, which could possibly improve the penetration of drugs such as proteins, peptides and other macromolecules to increase the systemic delivery of high molecular weight compounds with controlled input kinetics and minimum inter-subject variability. Although iontophoresis seems to be an ideal candidate to overcome the limitations associated with the delivery of ionic drugs, further extrapolation of this technique is imperative for translational utility and mass human application.     

Nanostructured lipid carriers as a delivery system of biochanin A

Abstract

The aim of this study was to explore the nanostructured lipid carriers as a delivery system of biochanin A so as to supply a method to improve its bioavailability. Biochanin A–loaded nanostructured lipid carriers (BCA-NLCs) were prepared by the method of emulsion-evaporation and low temperature solidification. Pharmacokinetics was carried out in rats upon oral administration at a dose of 10?mg/kg. BCA-NLC showed spherical formulation and had mean diameter174.68?±?0.96?nm, zeta potential ?20.9?±?0.8?mv and entrapment efficiency 97.36?±?0.14%. DSC and XRD studies indicated that BCA was not in crystal state in NLC. In in vitro release study, the BCA from BCA-NLC exhibited a biphasic release pattern with burst release initially and sustained release afterwards. BCA-NLC showed higher AUC value and circulated in blood for a longer time than BCA suspension. The studies demonstrated that NLC could be a potential delivery system for BCA to improve bioavailability.     

口服结肠定位给药系统

综述了近年来口服结肠定位给药系统的发展状况 ,并评价了各类结肠定位给药系统的优、缺点和发展前景     

HPMA在骨靶向药物输送方面的应用

本文简要的阐述了N-2-羟丙基-甲基丙烯酰胺聚合物(HPMA)在靶向药物输送方面的特性,并介绍了把N-2-羟丙基-甲基丙烯酰胺聚合物复合物应用在骨靶向方面的部分进展以及它们的体内体外的实验研究现状,以HPMA-D-Asp8-PGE1复合物为例介绍了N-2-羟丙基-甲基丙烯酰胺聚合物复合物的整体设计。     

Colloidal systems for the delivery of cyclosporin A to the anterior segment of the eye

Due to the eye's specific anatomical and physiological conformation, the treatment of eye diseases is a real challenge for pharmaceutical therapy. The presence of efficient protective barriers (i.e., the conjunctival and corneal membranes) and protective mechanisms (i.e., blinking and nasolachrymal drainage) makes this organ particularly impervious to local drug therapy. To overcome these issues, numerous strategies have been envisioned using pharmaceutical technology. Many formulations currently on the market or still under development are emulsions or colloidal systems intended to enhance precorneal residence time and corneal penetration, causing a consequent increase in drug bioavailability after instillation. After a review of some recent developments in the field of cyclosporin A formulations for the eye, a novel micellar formulation of cyclosporine A based on a diblock methoxy-poly(ethylene glycol)-hexysubstituted poly(lactides) (MPEG-hexPLA) is described.     

降钙素给药系统的研究进展

随着人类社会的老年化,骨质疏松症逐渐成为大众所关注的健康问题.相对其他治疗药物,降钙素由于其有效性和安全性,在抗骨质疏松症治疗的药物中越来越受到重视.现对其结构式、已上市品种及最新给药系统的研究情况及其进展进行了综述.