丙烯酸系列树脂在药物剂型中的应用

通过对丙烯酸树脂在薄膜包衣片、控释骨架片、固体分散体、微球、微囊、透皮给药系统和结肠定位给药等药物新剂型中的应用进行分析，认为随着丙烯酸树脂的开发研究，其在药物新剂型中的应用将越来越广泛。     

丙烯酸树脂在微丸包衣中的应用

本文对丙烯酸树脂系列辅料在微丸的缓释、控释、脉冲给药系统及定位给药系统等药物新剂型中的应用进行了综述。随着新型丙烯酸树脂的研究开发和制剂技术的发展,其在微丸中的应用更加广泛。     

药用丙烯酸树脂在微粒制剂中的应用状态综述

丙烯酸树脂具有成膜性能优良、各型号间相容性好等优点,近年来广泛应用于薄膜包衣、骨架制剂、微球、微囊及透皮等给药系统。本文对丙烯酸树脂系列辅料在微球和微囊制剂中的应用情况进行了综述。     

丙烯酸树脂在药物制剂中的应用

本文介绍了丙烯酸树脂的分类,以及在薄膜包衣、缓释骨架片、固体分散体、缓释微丸、口服定时/定位给药系统中的应用。     

替硝唑葡萄糖注射液的紫外分光光度测定

为了减小双氯灭痛对胃肠道刺激，减少服药次数，开发新的给药剂型，本研究分别以Ⅱ号丙烯酸树脂和Ⅳ号丙烯酸树脂为包衣材料，将其制成肠溶型级释微丸。体外溶出测定结果表明，该肠溶型缓释微丸在以人工胃液为溶出介质中，12h内无药物释放；在以人工肠液为溶出介质中，12h内最大释药百分率为84．5％，释药75％的时间为6h，达到缓释效果。     

卡托普利控释微丸的研制

目的：制备卡托普利控释微丸，并对其释药情况进行研究。方法：在流化床内，用丙烯酸树脂RL30D和丙烯酸树脂RS30D的混合物作为包衣材料制备卡托普利控释微丸，对包衣材料配比及包衣材料用量进行选择，对微丸体外释药方程进行研究，采用加速试验法考察微丸释药稳定性。结果：包衣材料最佳配比丙烯酸树脂RL30D-丙烯酸树脂RS30D为1：5，包衣材料最佳用量为包衣增重20％，微丸的体外释药方程为Q＝0．09614t-0．008379(r＝0．9980)，释药稳定性好。结论：卡托普利控释微丸具有良好的零级释药特征。     

药用丙烯酸树脂在制剂中的应用进展

目的:介绍药用丙烯酸树脂在药物制剂中应用的最新进展。方法:根据文献,以药用丙烯酸树脂中的德国商品尤特奇为代表,综述了该类辅料的理化性质及在制剂领域中的应用。结果:丙烯酸树脂根据溶解特性分为pH依赖型与pH非依赖型2种;主要用作缓控释制剂、口服定位释药系统、微球与微囊等制剂中的包衣材料及载体,可达到缓、控释或定位释放的目的,还可起到掩味、提高药物稳定性等作用。结论:丙烯酸树脂因具有多种功能和特殊性质而成为多种制剂的重要辅料,在制剂领域中具有广阔的前景。     

制备因素对丙烯酸树脂缓释微球中硝苯地平释放度的影响

用乳剂－溶剂挥发法制备硝苯地平的丙烯酸树脂缓释微球，微球中药物的释放速率随丙烯酸树脂Eudragit RL/RS比率的增加以及制备时搅拌速率的增加而增大，随内相聚合物浓度的增加及微球粒径的增加而减少，释药50％所需时间与微球粒径呈良好线性，微球的释药速率也随药物含量的增加（从4．2％到16．7％）而增大，并快于药物结晶的溶解速率，但药物含量达26．6％时，微球释药速率明显下并低于药物结晶的[溶解速率，用差热分析和X射线衍射分析证明，药物含量为4．2，9．4和16．7％的微球中药物完全是以非晶态分散的，而含药26．6％，的微球中有药物结晶存在，不同微球释药低于70％时，释放方式均符合Higuchi时间平方根方程。     

Influence of Preparation Factors on the Sustained Release of Nifedipine from Eudragit RL/RS Microspheres

用乳剂—溶剂挥发法制备硝苯地平的丙烯酸树脂缓释微球。微球中药物的释放速度随丙烯酸树脂ＥｕｄｒａｇｉｔＲＬ／ＲＳ比率的增加以及制备时搅拌速率的增加而增大，随内相聚合物浓度的增加及微球粒径的增加而减小，释药５０％所需时间与微球粒径呈良好线性。微球的释药速率也随药物含量的增加（从４．２％到１６．７％）而增大，并快于药物结晶的溶解速率，但药物含量达２６．６％时，微球释药速率明显下降并低于药物结晶的溶解速率。用差热分析和Ｘ射线衍射分析证明，药物含量为４．２，９．４和１６．７％的微球中药物完全是以非晶态分散的，而含药２６．６％的微球中有药物结晶存在。不同微球释药低于７０％时，释放方式均符合Ｈｉｇｕｃｈｉ时间平方根方程。     

微乳给药系统研究进展

微乳是一种新型给药系统，能提高水难溶性药物的溶解度和生物利用度，延长水溶性药物的释放，并具有较好的靶向性。近年来研究表明，微乳有利于药物的吸收、分布，可改善药动学，在透皮与口服给药、新制剂研发中得到应用。     

Drug release properties of polymer coated ion-exchange resin complexes: experimental and theoretical evaluation

Although ion-exchange resins have been used widely as drug delivery systems, their exact release kinetics has not been reported yet. Usually only the rate-limiting step has been taken into account and the rest of the steps have been ignored as instantaneous processes. To investigate the exact release kinetics of polymer-coated drug/ion-exchange resin complexes for sustained drug delivery, the results of new mathematical modeling were compared with experimental results. Drug/resin complexes with a model drug, dextromethorphan, were prepared and used as cores for fluid-bed coating. An aqueous colloidal dispersion of poly(vinyl acetate) was applied for the coating. A comprehensive mathematical model was developed using a mechanistic approach by considering diffusion, swelling, and ion-exchange processes solved by numerical techniques. The rate-limiting factor of the uncoated resin particles was diffusion through the core matrix. Similarly, in the coated particles the rate-limiting factor was diffusion through the coating membrane. The mathematical model has captured the phenomena observed during experimental evaluations and the release dynamics from uncoated and coated (at different coat levels) particles were predicted accurately (maximum RMSE 2.4%). The mathematical model is a useful tool to theoretically evaluate the drug release properties from coated ion-exchange complexes thus can be used for design purposes.     

镶嵌蒙脱石载体的离子交换微球给药系统的研制

目的以新型微纳米载体制备镶嵌蒙脱石的载药缓释微球离子交换给药系统。方法先考察蒙脱石对模型药盐酸倍他洛尔的静态吸附、动态吸附过程,后以丙烯酸树脂RS和RL,采用乳化-溶剂扩散法制备载药蒙脱石的缓释微球,对微球收率、载药量和包封率等理化性能进行考察。结果该法所制微球形态圆整,分布均匀,粒径在10～30μm之间。微球收率为101.9%,载药量为25.5%,包封率为45.84%。结论该微球制备工艺重复性较好,可用于制备镶嵌蒙脱石新型载体的离子交换给药系统。     

多层片给药系统在定位和控制释药中的应用

多层片给药系统由含药片层及屏障层组成，通过屏障层控制药物的释放。综述近年来该给药系统在缓控释方面的研究进展，介绍其在定位释药（颊部黏膜给药、胃内定位释药和结肠定位给药）和控制释药形式（双相型释药、零级释药、双峰型释药和延时型释药）方面的应用。     

Proprietary Rel-Ease drug delivery technology: opportunity for sustained delivery of peptides, proteins and small molecules

Proprietary Rel-Ease (Praecis Pharmaceuticals) drug delivery technology uses biocompatible polymers as carriers to incorporate a drug into a polymer matrix through opposite charge interaction or complexation. The resulting low solubility complexes can be used to prepare sustained release depot injections or potentially sustained release formulations for oral administration. As a regulatory approved and commercialised drug delivery technology, Rel-Ease is used in abarelix for injectable suspension, a monthly depot injection for the treatment of patients with advanced prostate cancer. The technology offers high drug loading and minimal-to-no initial burst effect in vivo. It uses aqueous processes and is compatible for complexation with many peptide and protein therapeutics; its mechanism can also be applied to many small-molecule therapeutics and offers conventional and alternative methods for sustained release delivery via an oral route.     

Proprietary Rel-Ease™ drug delivery technology: opportunity for sustained delivery of peptides,proteins and small molecules

Proprietary Rel-Ease? (Praecis Pharmaceuticals) drug delivery technology uses biocompatible polymers as carriers to incorporate a drug into a polymer matrix through opposite charge interaction or complexation. The resulting low solubility complexes can be used to prepare sustained release depot injections or potentially sustained release formulations for oral administration. As a regulatory approved and commercialised drug delivery technology, Rel-Ease is used in abarelix for injectable suspension, a monthly depot injection for the treatment of patients with advanced prostate cancer. The technology offers high drug loading and minimal-to-no initial burst effect in vivo. It uses aqueous processes and is compatible for complexation with many peptide and protein therapeutics; its mechanism can also be applied to many small-molecule therapeutics and offers conventional and alternative methods for sustained release delivery via an oral route.     

Simple preparation of coated resin complexes and their incorporation into fast-disintegrating tablets

Even though ion-exchange resins are good drug carriers to get sustained release properties, it may not be good enough only with themselves. For further sustained release effect, a diffusion barrier or coating on the resins’ surface can be utilized. Initially, microencapsulation using a w/o/w double emulsion method was used to apply ethylcellulose (EC) onto the drug/resin complexes. Typical pharmaceutical waxes can be alternative materials to delay the drug release from the complex. After the coating, the coated resin particles were incorporated into fast-disintegrating tablets to get an idea regarding the effects of wet granulation and compression on the release. Among the different grades of ECs tested (Ethocel® 20, 45, and 100), more viscous EC resulted in better morphologies and sustained release effects. Because the drug release rate was significantly dependent on the coating level, the release rate can be modified easily by changing different levels of the coating. The drug release rate was also strongly dependent on the granulation and compaction process as the coated particles were incorporated into the tablet dosage form. Among the tested waxes, stearic acid had an effect on the sustained release together with lubrication and wetting properties. Even though microencapsulation or wax coating may not be practical for real manufacturing, the results may give valuable information how to formulate sustained release dosage forms and their properties on the tablet preparation.     

大内径多壁碳纳米管基靶向缓释载药系统的制备及性能

目的制备大内径多壁碳纳米管（LID-MWCNT）基靶向抗肿瘤药物缓释系统,分析其功能特性并检测其对肿瘤细胞的增殖抑制作用。方法纯化、切割LID-MWCNT,制备碳管载体及同源封堵物超短LID-MWCNT （UST）。碳管表面负载靶向分子叶酸（FA）及荧光标记分子;管内负载抗肿瘤药物顺铂（CDDP）,并以UST 封堵药物通道。观察载药系统显微形态;测定载药率及药物释放曲线;观察载药系统对肿瘤细胞的靶向趋化状况及增殖抑制效应。结果成功制备大内径多壁碳纳米管基靶向抗肿瘤药物缓释系统（CDDP@UST-FA-LID-MWCNT）,其载药率为70.97%。体外释放呈双相缓释模式,持续释放时间约18 h。载体系统具备了一定靶向趋化能力;较低载药浓度的 CDDP@UST-FA-LID-MWCNT 即对肿瘤细胞具有增殖抑制作用,且随着药物浓度的增加,抑制作用增强。结论载药系统CDDP@UST-FA-LID-MWCNT 具有较高的载药率及良好的药物缓释效果,能够靶向作用于肿瘤细胞,具有较强的抗肿瘤作用。     

离子交换树脂在药剂学中的应用进展

离子交换树脂药物载体在给药系统中的应用由于具有很多优点而得到了人们的重视。目前在控释、透皮给药、定位给药、速溶、离子导入透皮、鼻腔、局部给药和掩盖药物苦味等方面都有很深入的研究，在缓控释给药中占有特殊的地位。综述了这一药物载体在给药系统和作用部位应用的新进展，并对其应用前景进行了展望。     

Development of pulsatile systems for targeted drug delivery of celecoxib for prophylaxis of colorectal cancer

The aim of the present study was to formulate fast release enteric-coated tablets for drug delivery to the colon. Two different approaches were used for the preparation of these tablets. The first included making use of superdisintegrant (SD) in the tablet. The amount of super disintegrant (cross-linked PVP) in the tablet and the coat weight were varied to formulate a suitable time-controlled release system, that would provide colon-specific drug delivery. The second approach consisted of development of osmogen-based tablets for drug delivery into the tracts of the colon. Two different osmogens, sodium chloride and potassium chloride, were used. These also were coated at different coat levels. Celecoxib was used as a model drug. In vitro drug release studies showed that superdisintegrants were more effective in showing burst effect in the tablets and therefore showed a rapid drug release as compared with osmogens, which would show a sustained drug release all through the colon. Osmotic tablets were formulated making use of a high concentration of osmogen sodium chloride (OM-SC) and potassium chloride (OM-KC) were further enteric-coated. These also were found to be useful in providing a sustained delivery of nearly 80-90% of the drug into the colonic region. The coat weight required in these tablets for protection in the upper gastrointestinal conditions varied from 9.69% in OM-KC tablets to 4.65% in OM-SC tablets.