环糊精包合技术及其在中药药剂中的应用

目的探讨环糊精包合技术及其在中药药剂中的应用。方法随机抽取近几年来环糊精包合技术及其在中药药剂中的应用的资料作为研究对象进行综合分析。结果环糊精包合技术及其在中药药剂中的应用具有抑制药物挥发、降低药物刺激性、减少药物不良反应的效果，大大提高药物的溶解度和药物稳定性。结论环糊精包合技术及其在中药药剂中的应用，效果良好，值得临床应用与推广。     

缓控释技术及其口服制剂开发应用进展

随着固体分散技术、环糊精包合技术、微型包囊与微型成球技术、脂质体、微乳等缓控释新技术的不断开发,越来越多的口服缓控释制剂得到应用。缓释片、控释液体制剂、缓释干混悬剂等新剂型的研究日渐深入,其应用将越来越广泛。     

难溶性药物的增溶及其缓/控释制剂研究进展

目前由高通量药物筛选而得的活性物质约有40％是水难溶性的，难溶性药物（poorly water—soluble drug）因其在水中溶解度小，药物难以被机体吸收，体内消除速度较快，血药浓度容易出现峰谷现象，口服制剂生物利用度低，且难以实现剂型的多样化。已报道的增溶技术如固体分散技术、环糊精包合技术、胶束增溶、微乳增溶、超微粉碎等已用于增加难溶性药物的溶解度，提高其口服制剂的生物利用度。缓／控释制剂（sustained or controlled release dosage forms）具有减少用药总剂量和用药次数，避免血浓峰谷现象，降低毒副作用，提高病人顺应性等优点，在临床上的应用日益广泛。目前应用增溶技术和缓／控释技术提高难溶性药物的溶解度和生物利用度，研制难溶性药物的缓／控释制剂以成为药剂学研究的热点方向。本文就难溶性药物的增溶及其缓／控释制剂的研究进展做如下综述。     

环糊精在药物制剂方面的新应用

环糊精及其衍生物在改善药物理化性质、改进处方、提高药效等方面具有重要价值，尤其在靶向及微粒给药系统等尖端制剂技术方面的应用越来越广泛。对环糊精及其衍生物在速释和缓释制剂、控释给药、定位给药、微粒给药系统、药物微粉化等方面的发展现状进行了综述，以促进国内在这方面的研究。     

分子动力学模拟技术在自组装纳米递药系统研究中的应用进展

分子动力学模拟技术是一种依靠牛顿力学模拟分子体系的运动来研究现实系统的计算机模拟方法,近年来逐渐被用于自组装纳米递药系统的自组装过程揭示及宏观性能预测,有助于高效率、精准化设计制剂。本综述从分子动力学模拟技术的定义、类型及操作流程出发,总结了其在自组装纳米递药体系研究中的应用,包括自组装过程微观信息(尺寸形貌、微区组成、分子分布)的获取与分析、宏观性能(稳定性、载药能力、释药性及跨膜性能)的预测,并对其在递药系统处方预测中的应用进行了归纳,同时展望了未来实现制剂处方预测的策略,旨在为制剂研究人员选择适宜的路径研究纳米体系提供理论依据,为分子动力学模拟技术在制剂领域更广阔的应用提供参考。     

β－环糊精包合技术在中药药剂中的应用

本文就2003年以后，以β－环糊精在中药药剂包合中的主要作用为分类，对β－环糊精包合技术在中药药剂方面的应用作一综述。     

包合技术在中药药剂学中的应用

现代药剂学已进入了药物传递系统（Drug delivery system，DDS）的时代，利用新材料、新技术开发中药新剂型已成为当前中药制剂研究中的一项重要课题。包合技术是指一种分子被包藏在另一种分子的空穴结构内形成包合物的技术。药物作为客分子经包合后，溶解度增大，稳定性提高，液体药物可微粉化，可防止挥发性成分的挥发，掩盖药物的不良气味或味道，调节释放速率，提高药物的生物利用度，降低药物的刺激性与毒副作用。正是由于这些优点，包合技术越来越受到药剂工作者的青睐。常用的包合材料有环糊精（Cyclodextrin，CD）、胆酸、淀粉、纤维素、蛋白质、核酸等。目前，在制剂中最常用的是CD及其衍生物。CD有多种同系物，常见的CD是由6～8个葡萄糖分子通过1，4-苷键连接而成的环状化合物，分别称之为α—CD、β—CD和γ-CD。经X-射线衍射和核磁共振研究表明，CD的立体结构是一个环状中空的圆筒形，分子内部以氧原子为主，具有疏水性，分子外部以羟基为主，具有亲水性。     

固体分散技术及其在缓控释制剂中的应用

固体分散体（Solid Dispersion,简称SD）系指药物以微粒、微晶或分子状态等形式均匀分散在固态载体物质中的体系。由于SD能够增加一些难溶性药物的溶解度和释放速度、提高口服生物利用度,已受到各国学者普遍关注。近年来SD技术应用于缓控释制剂的研究日益增多。本文对SD的作用特点、载体材料、释药机制、稳定性及近年来固体分散技术在缓控释制剂中的应用作一概述。     

环糊精纳米给药系统在药物传递中的应用

目的对目前环糊精纳米给药系统的应用进行综述。方法参考近年来国内外文献共28篇,根据纳米制剂形成的驱动力不同将常见的环糊精纳米制剂分为四类进行分类和评述。结果基于环糊精的纳米给药系统综合应用环糊精包合技术和纳米技术共同改善药物的性质。根据形成纳米制剂的驱动力不同,主要分为四类:主分子—客分子介导的环糊精纳米载体、两亲性环糊精衍生物纳米粒、基于环糊精的聚合物纳米粒、无机环糊精纳米粒。同时介绍了环糊精纳米制剂的药剂学应用、研究进展以及发展前景。结论 环糊精纳米给药系统不仅能解决纳米粒载药量过低的缺点,还能达到靶向性,显著提高难溶性药物的生物利用度,极具发展前景和应用价值。     

CAChe6.1模拟软件优选灯盏花素环糊精包合工艺

目的:优选灯盏花素环糊精包合工艺。方法:以灯盏花素与不同环糊精包合物能量变化值为指标,通过CAChe6.1软件模拟灯盏花素环糊精包合过程并优选包合灯盏花素的最佳环糊精类型。结果:α-环糊精包合灯盏花素效果最佳,能量变化值最小,为14 k/mol。结论:该模拟软件优选工艺节省了大量时间,使具体试验得到优化。     

Effect of hydroxypropyl-beta-cyclodextrin on hydrocortisone dissolution from films intended for ocular drug delivery

The formation of an inclusion complex between hydrocortisone and hydroxypropyl-beta-cyclodextrin can affect the in vitro transfer rate of hydrocortisone from the aqueous to the organic phase. The observed first order transfer rate constants showed that the complexation of hydrocortisone with hydroxypropyl-beta-cyclodextrin decreased significantly the transport of the drug depending on the partition coefficient of the drug, and the relative magnitude of the stability constant of the inclusion complex. To optimize the ocular drug delivery, high molecular weight cellulosis and PVA polymeric films were prepared. No unified mathematical model can predict the release profile of drug and complex from films. The drug and complex-polymer interactions in each system could be responsible for the solubility of the drug, and different release behaviours of hydrocortisone and cyclodextrin inclusion complex from the films prepared.     

Cyclodextrins in topical drug formulations: theory and practice

Cyclodextrins are cyclic oligosaccharides with a hydrophilic outer surface and a somewhat lipophilic central cavity. Cyclodextrins are able to form water-soluble inclusion complexes with many lipophilic water-insoluble drugs. In aqueous solutions drug molecules located in the central cavity are in a dynamic equilibrium with free drug molecules. Furthermore, lipophilic molecules in the aqueous complexation media will compete with each other for a space in the cavity. Due to their size and hydrophilicity only insignificant amounts of cyclodextrins and drug/cyclodextrin complexes are able to penetrate into lipophilic biological barriers, such as intact skin. In general, cyclodextrins enhance topical drug delivery by increasing the drug availability at the barrier surface. At the surface the drug molecules partition from the cyclodextrin cavity into the lipophilic barrier. Thus, drug delivery from aqueous cyclodextrin solutions is both diffusion controlled and membrane controlled. It appears that cyclodextrins can only enhance topical drug delivery in the presence of water.     

Influence of hydroxypropyl-beta-cyclodextrin complexation on piroxicam release from buccoadhesive tablets.

Interaction of piroxicam (PX) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) was investigated in solution and in the solid state. Solubility studies demonstrated the formation of the PX-HPbetaCD inclusion complex with 1:1 stoichiometry. Equimolecular PX-HPbetaCD solid systems were prepared and characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, and X-ray diffractometry. Modification of the release of a sparingly water-soluble drug, PX, from hydrophilic matrices using cyclodextrin complexation was evaluated. The buccoadhesive controlled release tablets for the delivery of PX were prepared by direct compression of hydroxypropylmethyl cellulose (HPMC) and Carbopol 940 (C940), which showed superior bioadhesion properties compared to HPMC. The tablets were evaluated for their dissolution, swelling and mucoadhesive properties. The in vitro release results demonstrated that matrix tablets containing the PX-HPbetaCD solid complex displayed faster PX release compared to those containing a physical mixture or "free" drug. Differences in release rates of PX from the tablets could be attributed to the presence of the polymers and to cyclodextrin complexation. The effect of the polymers on PX release can affect the drug solubility (complexation) and polymer water uptake (swelling). Higher polymer water uptake may result in higher drug solubility and diffusivity in a hydrated polymeric environment. Drug complexation affected also its diffusivity through the semipermeable membrane.     

Comparative evaluation of polymeric and amphiphilic cyclodextrin nanoparticles for effective camptothecin delivery

Camptothecin (CPT) is a potent anticancer agent. The clinical application of CPT is restricted by poor water solubility and instability under physiological conditions. Solubilization and stabilization of CPT were realized through nanoparticulate systems of amphiphilic cyclodextrins, poly(lactide-co-glycolide) (PLGA) or poly-ε-caprolactone (PCL). Nanoparticles were prepared with nanoprecipitation technique, whereas cyclodextrin nanoparticles were prepared from preformed inclusion complexes of CPT with amphiphilic cyclodextrins. Polymeric nanoparticles, on the other hand, were loaded with CPT:HP-β-CD inclusion complex to solubilize and stabilize the drug. Mean particle sizes were under 275 nm, and polydispersity indices were lower than 0.2 for all formulations. Drug-loading values were significantly higher for amphiphilic cyclodextrin nanoparticles when compared with those for PLGA and PCL nanoparticles. Nanoparticle formulations showed a significant controlled release profile extended up to 12 days for amphiphilic cyclodextrin nanoparticles and 48 h for polymeric nanoparticles. Anticancer efficacy of the nanoparticles was evaluated in comparison with CPT solution in dimethyl sulfoxide (DMSO) on MCF-7 breast adenocarcinoma cells. Amphiphilic cyclodextrin nanoparticles showed higher anticancer efficacy than PLGA or PCL nanoparticles loaded with CPT and the CPT solution in DMSO. These results indicated that CPT-loaded amphiphilic cyclodextrin nanoparticles might provide a promising carrier system for the effective delivery of this anticancer drug having bioavailability problems.     

Cyclodextrins in drug carrier systems

One of the important characteristics of cyclodextrins is the formation of an inclusion complex with a variety of drug molecules in solution and in the solid state. As a consequence of intensive basic research, exhaustive toxic studies, and realization of industrial production during the past decade, there seem to be no more barriers for the practical application of natural cyclodextrins in the biomedical field. Recently, a number of cyclodextrin derivatives and cyclodextrin polymers have been prepared to obtain better inclusion abilities than parent cyclodextrins. The natural cyclodextrins and their synthetic derivatives have been successfully utilized to improve various drug properties, such as solubility, dissolution and release rates, stability, or bioavailability. In addition, the enhancement of drug activity, selective transfer, or the reduction of side effects has been achieved by means of inclusion complexation. The drug-cyclodextrin complex is generally formed outside of the body and, after administration, it dissociates, releasing the drug into the organism in a fast and nearly uniform manner. In the biomedical application of cyclodextrins, therefore, particular attention should be directed to the magnitude of the stability constant of the inclusion complex. In the case of parenteral application, a rather limited amount of work has been done because the cyclodextrins in the drug carrier systems have to be more effectively designed to compete with various biological components in the circulatory system. However, the works published thus far apparently indicate that the inclusion phenomena of cyclodextrin analogs may allow the rational design of drug formulation and that the combination of molecular encapsulation with other carrier systems will become a very effective and valuable method for the development of a new drug delivery system in the near future.     

Cyclodextrin-based supramolecular systems for drug delivery: Recent progress and future perspective

The excellent biocompatibility and unique inclusion capability as well as powerful functionalization capacity of cyclodextrins and their derivatives make them especially attractive for engineering novel functional materials for biomedical applications. There has been increasing interest recently to fabricate supramolecular systems for drug and gene delivery based on cyclodextrin materials. This review focuses on state of the art and recent advances in the construction of cyclodextrin-based assemblies and their applications for controlled drug delivery. First, we introduce cyclodextrin materials utilized for self-assembly. The fabrication technologies of supramolecular systems including nanoplatforms and hydrogels as well as their applications in nanomedicine and pharmaceutical sciences are then highlighted. At the end, the future directions of this field are discussed.     

Synthesis and evaluation of the mucoadhesivity of a CD-chitosan derivative

Combining mucoadhesive characteristics of a biodegradable polymer such as chitosan with the potential to enhance drug release by increasing the solubility of poorly water-soluble drugs has great potential for pharmaceutical technology and drug delivery design. Polymeric delivery systems have been extensively researched in an attempt to achieve modified drug release. Cyclodextrins (CD) offer an alternative approach. These cyclic oligosaccharides have the ability to form non-covalent complexes with a number of drugs altering their physicochemical properties. In the continuing challenge to improve the properties of delivery systems, this paper focuses on the modification of chitosan by introducing beta-cyclodextrin and to test the mucoadhesive strength and inclusion properties of this synthesised cyclodextrin-polymer. beta-Cyclodextrin was successfully grafted onto a chitosan chain polymer with a cyclodextrin grafting yield of 7% and a CD-chitosan yield of 85%. Although the complexation of (+)-catechin by the grafted beta-CD was found to be about five times weaker than that by the beta-CD monoaldehyde and natural beta-CD, the inclusion properties of the chitosan-CD remain promising. The mucoadhesive properties of chitosan-CD were compared to that of pectin (reference) and the parent chitosan with the use of a tensile separation test. The chitosan-CD showed mucoadhesive strengths of 12% stronger than pectin, but 13.5% weaker than the parent chitosan. The synthesised chitosan-CD-polymer exhibits characteristics of a possible mucoadhesive drug delivery system with some inclusion properties from beta-cyclodextrin.     

口服固体自微乳化给药系统的研究进展

目的对新近发展的固体自微乳化给药系统（S-SMEDDS）文献进行综述。方法查阅近年国内外相关文献并进行归纳和总结。结果对固体自微乳的载体、固化技术以及缓控释制剂进行了探讨,为研究水难溶性药物的生物利用度及适合药物释放特性的S-SMEDDS技术提供相关参考。结论固体自微乳化系统可以显著提高难溶性药物的口服生物利用度,且兼顾了液态自微乳和固体制剂二者的优势,是一个极具潜力的新型制剂。     

Bovine serum albumin nanospheres carrying progesterone inclusion complexes

Bovine serum albumin nanospheres carrying cyclodextrin complexes for the delivery of progesterone were produced. Inclusion complexes composed of progesterone and hydroxypropyl-β -cyclodextrin or dimethyl-β -cyclodextrin were prepared by spray-drying or freeze-drying methods. Prog alone and its inclusion complexes were incorporated into bovine serum albumin nanospheres using a coacervation method and cross-linking with heating. The nanosphere suspensions were essicated by spray-drying or freeze-drying. The inclusion complexes and the nanospheres were characterized by Fourier Transform-Infrared Spectroscopy (FT-IR) and Differential Scanning Calorimetry (DSC). Phase-solubility diagrams and stability constants were determined in distilled water at different temperatures (10, 25, and 37°C). Size of nanospheres, their drug loading capacity and swelling ability were evaluated, as well as the in vitro controlled release profiles at pH 5.5 and 7.4.