新型凝胶给药系统研究进展

凝胶在现代药学中应用广泛,以凝胶为基质的缓释控释剂型,如胃滞留控释系统、凝胶骨架片等,得到了全面的研究。适用于凝胶给药系统的药物甚多,亲水性药物、疏水性药物、酸性药物、阳离子药物、大分子药物、细胞组织等均可作为它的模型药物。而且可以从口腔、鼻腔、眼粘膜、消化道粘膜、阴道、直肠、皮肤等途径给药。     

原位凝胶在黏膜给药制剂中的研究进展

原位凝胶是一种新型给药系统,按其形成机制可分为温度敏感型、离子敏感型、pH敏感型等类型。该文就原位凝胶在眼部给药、鼻腔给药及直肠给药方面的应用作一概述,提出原位凝胶应用中存在的问题,并对其良好应用前景进行展望。     

温敏水凝胶在智能给药系统中的应用

温敏水凝胶能随环境温度的变化而发生可逆性的体积变化，利用这种性质，将其应用于给药系统可以实现响应环境温度变化的智能化给药。在这种新型的给药系统中，温敏水凝胶可以是骨架材料，也可制成控释膜、微球、胶团等形式。本文介绍温敏水凝胶的性质以及在给药系统中的应用和释药机理。     

阴道内给药凝胶制剂的研究进展

随着药用高分子材料的发展,阴道给药凝胶制剂将会成为一种具有发展前景的腔道给药制剂.本文通过对近年来有代表性的文献进行分析和归纳,介绍了阴道用凝胶剂的研究进展,为其深入研究提供参考.随着阴道系统给药吸收机制研究的深入及药用高分子材料的发展,相信不久的将来会有稳定的、更方便的、生物利用度更高的凝胶制剂问世.     

温敏水凝胶在智能给药系统中的应用

温敏水凝胶能随环境温度的变化而发生可逆性的体积变化，利用这种性质，将其应用于给药系统可以实现响应环境温度变化的智能化给药，在这种新型的给药系统中，温敏水泵凝胶可以是骨架材料，也可制成控释膜，微球，胶团等形成，本文介绍温敏水凝胶的性质以及在给药系统中的应用和释药机理。     

微乳凝胶经皮给药制剂的研究与应用进展

目的 介绍微乳凝胶经皮给药制剂的研究与应用进展。方法 根据近年来国内外相关文献,对微乳凝胶作为经皮给药载体的处方筛选、制备、体外释药性能、质量检查、研究应用进展等方面进行介绍。结果 微乳凝胶具有显著增强药物的经皮渗透能力、降低药物刺激性和延缓药物释放等作用,且更便于给药。结论 微乳凝胶有望成为一种具有重要应用价值的经皮给药新剂型。     

鼻用原位凝胶给药系统中药物吸收的影响因素与改进措施

药物的吸收主要是由药物的理化性质、剂型以及给药途径所决定的。原位凝胶是指在生理条件刺激下能发生分散状态或构象的可逆变化、完成溶液与凝胶间相互转变的新剂型。原位凝胶经鼻腔给药,既避免了药物的胃肠首过效应,又因其能延长药物在给药部位滞留时间,从而避免药物被鼻纤毛快速清除。本文通过系统查阅近年国内外鼻用原位凝胶给药系统的相关文献,就鼻腔的生理特点、药物理化性质与原位凝胶的制剂处方等影响其药物吸收的主要因素及改进措施,进行分析、整理和归纳,旨在为鼻用原位凝胶给药系统的设计与质量控制提供参考。     

温敏凝胶的研究与应用进展

目的:为温敏凝胶的研发及临床应用提供相关理论参考。方法:以"温敏凝胶""作用机制""辅料""给药途径""Temperature-sensitive gel""Mechanism""Accessories""Route of administration"等为关键词,组合检索2009-2014年Pub Med、中国知网、万方等数据库,对温敏凝胶的作用机制、释药模式、给药途径及应用情况等作简要综述。结果与结论:温敏凝胶通过改变分子间的作用力,使聚合物之间的相互作用发生改变,随着温度升高而形成凝胶。其中常用的是丙烯酰胺类,主要释药模式包括挤压式、正反"开-关"式、压力作用式等。采用注射、口腔、耳内、鼻腔、眼内、皮肤等多种给药方式,使药物在人体内发挥很好的缓释作用,降低药物毒性,防止药物外渗,提高药物的稳定性,比同类药物的其他剂型更有优势。随着温敏凝胶研究和应用的不断深入,其作为一种新型剂型,有望在肿瘤、中药新剂型等方面得到更好的应用。     

眼用凝胶剂研究进展

凝胶剂因其优良的成型性、黏弹性、载药量、生物相容性好和眼部滞留时间长的优点,已广泛应用于眼部给药系统.根据国内外眼用凝胶剂的研究现状,本文简要综述了眼用凝胶剂的性质、分类、常用的聚合物及应用情况等.     

凝胶材料及其在经皮给药系统中的应用与研究进展

凝胶材料具有触感舒适、透气性好、高粘弹性等其他材料所无法比拟的优势,在经皮给药系统中备受青睐,被广泛应用于现代经皮给药制剂如贴剂、贴膏剂、凝胶剂、膜剂当中。随着医药材料的创新发展,许多具有优异功能的新型凝胶材料涌现,使经皮给药制剂的应用范围得到扩大,性能得以优化。通过综述凝胶材料的分类、性能及其在经皮给药系统中的应用,总结最新研究进展,为凝胶材料在经皮给药系统的创新应用提供借鉴和参考。     

Organogels in drug delivery

In the last decade, interest in physical organogels has grown rapidly with the discovery and synthesis of a very large number of diverse molecules, which can gel organic solvents at low concentrations. The gelator molecules immobilise large volumes of liquid following their self-assembly into a variety of aggregates such as rods, tubules, fibres and platelets. The many interesting properties of these gels, such as their thermoreversibility, have led to much excitement over their industrial applications. However, only a few organogels are currently being studied as drug/vaccine delivery vehicles as most of the existing organogels are composed of pharmaceutically unacceptable organic liquids and/or unacceptable/untested gelators. In this paper a brief overview of organogels is presented, followed by a more in-depth review of the gels that have been investigated for drug and/or vaccine delivery. These include microemulsion-based gels and lecithin gels (studied for transdermal delivery), sorbitan monostearate organogels and amphiphilogels (studied as vaccine adjuvants and for oral and transdermal drug delivery, respectively), gels composed of alanine derivatives (investigated as in situ forming gels) and Eudragit organogels (studied as a matrix for suppositories). Finally, pluronic lecithin organogels, descendents of lecithin gels but which are not really organogels, are briefly discussed for their interesting history, their root and the wide interest in these systems.     

Organogels in drug delivery

In the last decade, interest in physical organogels has grown rapidly with the discovery and synthesis of a very large number of diverse molecules, which can gel organic solvents at low concentrations. The gelator molecules immobilise large volumes of liquid following their self-assembly into a variety of aggregates such as rods, tubules, fibres and platelets. The many interesting properties of these gels, such as their thermoreversibility, have led to much excitement over their industrial applications. However, only a few organogels are currently being studied as drug/vaccine delivery vehicles as most of the existing organogels are composed of pharmaceutically unacceptable organic liquids and/or unacceptable/untested gelators. In this paper a brief overview of organogels is presented, followed by a more in-depth review of the gels that have been investigated for drug and/or vaccine delivery. These include microemulsion-based gels and lecithin gels (studied for transdermal delivery), sorbitan monostearate organogels and amphiphilogels (studied as vaccine adjuvants and for oral and transdermal drug delivery, respectively), gels composed of alanine derivatives (investigated as in situ forming gels) and Eudragit organogels (studied as a matrix for suppositories). Finally, pluronic lecithin organogels, descendents of lecithin gels but which are not really organogels, are briefly discussed for their interesting history, their root and the wide interest in these systems.     

An examination of the rheological and mucoadhesive properties of poly(acrylic acid) organogels designed as platforms for local drug delivery to the oral cavity

This study examined the rheological/mucoadhesive properties of poly(acrylic acid) PAA organogels as platforms for drug delivery to the oral cavity. Organogels were prepared using PAA (3%, 5%, 10% w/w) dissolved in ethylene glycol (EG), propylene glycol (PG), 1,3-propylene glycol (1,3-PG), 1,5-propanediol (1,5-PD), polyethylene glycol 400 (PEG 400), or glycerol. All organogels exhibited pseudoplastic flow. The increase in storage (G') and loss (G') moduli of organogels as a function of frequency was minimal, G' was greater than G' (at all frequencies), and the loss tangent <1, indicative of gel behavior. Organogels prepared using EG, PG, and 1,3-propanediol (1,3-PD) exhibited similar flow/viscoelastic properties. Enhanced rheological structuring was associated with organogels prepared using glycerol (in particular) and PEG 400 due to their interaction with adjacent carboxylic acid groups on each chain and on adjacent chains. All organogels (with the exception of 1,5-PD) exhibited greater network structure than aqueous PAA gels. Organogel mucoadhesion increased with polymer concentration. Greatest mucoadhesion was associated with glycerol-based formulations, whereas aqueous PAA gels exhibited the lowest mucoadhesion. The enhanced network structure and the excellent mucoadhesive properties of these organogels, both of which may be engineered through choice of polymer concentration/solvent type, may be clinically useful for the delivery of drugs to the oral cavity.     

定量吸入气雾剂处方设计应考虑的几个问题

肺部具有吸收表面积大、吸收部位血流丰富、可避免肝脏首过效应以及上皮屏障薄、膜通透性高等优点,因此,采用定量吸入喷雾剂进行肺部给药得到极大的重视。现参考美国FDA、欧盟关于吸入制剂相关指导原则,并结合国内气雾剂的研发和生产的具体情况和我国药典,对定量吸入气雾剂的处方设计中应该考虑的一些主要问题进行了综述。     

Application of organogels as oral controlled release formulations of hydrophilic drugs

We previously demonstrated that organogels prepared from soybean oil using 12-hydroxy stearic acid as a gelator can slowly release ibuprofen, a model lipophilic drug. In this study, we investigated the applicability of organogels as controlled release formulations of hydrophilic drugs. The release rates of theophylline and ofloxacin, which are used as model hydrophilic drugs, were significantly slower than those of ibuprofen and antipyrine (model lipophilic drugs). Furthermore, no erosion was noted during drug release from organogels. Lipophilic drug molecules are released after diffusion in organogels because all molecules fully dissolve in the gel. On the other hand, hydrophilic drug molecules need to be dissolved before they diffuse in the organogel, prior to their release from the gel. Therefore, it is speculated that the release rates of hydrophilic drugs are slower than those of lipophilic drugs. To confirm the usefulness of organogels in controlled release formulations in vivo, organogels containing ibuprofen, ofloxacin, theophylline or antipyrine were intraduodenally administered to rats. All drugs used in this study were rapidly absorbed when administered in aqueous suspensions. In contrast, the drug concentrations in plasma after administration in organogels were lower; however, the lower concentrations of drugs sustained for 10h after administration. With organogel administration, the mean residence time of drugs was longer than that with aqueous suspension administration. In conclusion, organogels are potential candidates for controlled release formulations of not only lipophilic drugs, but also hydrophilic drugs.     

在体成形给药系统

综述热塑胶浆、在体交联、在体聚合物沉淀和在体固化有机凝胶4种在体成形给药系统的制备原理。蛋白质类药物局部注射埋植给药已成为研究热点,在体成形技术已广泛用于医药学领域,如注射埋植给药、眼部植入给药、口服给药和组织修复等。简介该类给药制剂的流变学和体内外评价方法。     

Topical Delivery of Flurbiprofen from Pluronic Lecithin Organogel

The purpose of this research is to formulate and evaluate the suitability of pluronic lecithin organogels containing flurbiprofen for topical application. Four formulations were developed using flurbiprofen, lecithin, Pluronic F127, isopropyl palmitate, water, sorbic acid and potassium sorbate were coded as FL1, FL2, FL3 and FL4. All the formulations carried 30% w/w of lecithin phase and 70% w/w of Pluronic phase. The formulated organogels were evaluated for appearance and feel psychorheologically, in vitro diffusion study, drug content, viscosity and pH. Release of flurbiprofen from all formulations was monitored via dialysis membrane-70 and Wistar rat skin as a semipermeable membrane into phosphate buffer saline (0.2 M, pH 7.4) using Keshary-Chien diffusion cell. The viscosities of different formulations were determined by using Brookfield Viscometer at 25°. An attempt has been made to explore the potential of pluronic lecithin organogels for topical delivery of flurbiprofen.     

The reformulation of Amphotericin B for oral administration to treat systemic fungal infections and visceral leishmaniasis

Amphotericin B (AmB) is a parenterally administered broad-spectrum antifungal and leishmanicidal drug that has been on the market for over sixty years. Unfortunately, significant infusion-related side effects and renal toxicity often accompany treatment, limiting its clinical applications. Lipid-based formulations have somewhat ameliorated the associated toxicity, but the increased cost of formulations restricts widespread use. AmB is amphipathic and exhibits low solubility and permeability, resulting in negligible absorption when administered orally. Advances in drug delivery systems have overcome some of the solubility issues that prevent oral bioavailability and new formulations are currently in development. The existence of an effective, safe and inexpensive oral formulation of amphotericin B would have significant applications for the treatment of disseminated fungal infections and would dramatically expand access to treatment of visceral leishmaniasis by introducing a readily available highly tolerated oral formulation of a drug with known efficacy.     

Gelatin-stabilised microemulsion-based organogels facilitates percutaneous penetration of Cyclosporin A in vitro and dermal pharmacokinetics in vivo

Gelatin-stabilised microemulsion-based organogels (MBGs) are very useful in transdermal and topical delivery of hydrophobic drugs because of their lipophilic nature. MBGs systems possessing a potentially improved skin bioavailability of Cyclosporin A were designed and explored for some characteristics. The release characteristics of drug from MBGs were studied according to drug concentration. As the concentration of drug increased, the release of drug from gel increased, showing concentration dependency. Percutaneous penetration studies using rat skin in vitro showed that the deposition of Cyclosporin A was significantly improved by MBGs compared to the control. We also evaluated the therapeutic advantage of dermal administration of Cyclosporin A in rat model. Local (subcutaneous and skin), systemic concentrations and organ distribution (liver and kidney) were evaluated serially following topical and oral application of the drug. In rat dermal applied with the MBGs containing Cyclosporin A, the deposition of the drug into skin and subcutaneous fat was, respectively, almost 55- and 3-fold higher than the concentrations compared with oral administration. Systemic distribution in blood, liver and kidney was much lower following topical than following oral administration. With high local concentrations and minimal distribution to other organs via the circulation, topical applied MBGs loaded with Cyclosporin A might deliver maximal therapeutic effect to local tissue while avoiding the side effects seen with systemic therapy. The histopathological findings revealed that the new MBGs vehicle was a safe vehicle for topical drug delivery systems.     

智能材料在药剂学中的分类与应用

目的为智能材料在药剂学中的应用提供理论依据。方法通过查阅近年国内外文献,对物理、化学和生物化学刺激敏感型智能材料的分类、各类材料构建相应智能给药系统的设计原理及其在药剂学中的应用进行详细的阐述。结果应用智能材料可制备出各种智能给药系统,通过感应病变部位各种环境信息的变化,实现药物的定点、定时、定量释放。结论虽然智能材料的应用迄今为止多数仍停留在实验研究阶段,但可以预见智能材料在药剂学领域中的应用会显现出更大的优势。