pH敏感型羧甲基壳聚糖水凝胶的制备及体外释药考察

目的:研制一种新型羧甲基壳聚糖基pH敏感性水凝胶,考察其在药物传输体系中的应用.方法:采用钙离子交联方法制备有良好pH响应性能的羧甲基壳聚糖基水凝胶,并对其pH响应性能进行相关的表征.以磺胺嘧啶钠为模型药物,考察载药水凝胶在不同pH环境条件下(pH =2和pH =7.4)的药物释放行为.结果:所制备的羧甲基壳聚糖水凝胶具有明显的孔洞结构和良好的pH响应性能,在中性磷酸盐缓冲溶液(pH=7.4)中吸水率显著大于在酸性溶液(pH=2)中的吸水率.载有磺胺嘧啶钠的羧甲基壳聚糖水凝胶在中性磷酸盐缓冲溶液(pH=7.4)中的4h的药物累计释放率达到95％,而在酸性溶液(pH=2)中的4h的药物累计释放率却只有50％.结论:本文所制备的羧甲基壳聚糖pH敏感性水凝胶具有良好的孔隙率和pH响应性能,在口服药物传输体系中有一定的应用前景.     

氨苯砜包合物凝胶的体外释放度考察

摘要目的探讨氨苯砜（DDS）凝胶的体外释放规律及释放动力学。方法采用透析法研究1%,2%DDS包合物凝胶和2%DDS普通凝胶的体外释药特征。结果DDS包合物凝胶26 h基本完全释放,而DDS普通凝胶仅释放64%,3种凝胶的体外释放过程符合Higuchi方程。DDS经包合后释放速率较快。结论DDS包合物制备的凝胶具有加快释药的释放特征。     

复方替硝唑水凝胶栓体外释放度考察

<正>复方替硝唑水凝胶栓是我院在复方替硝唑栓的基础上更改剂型研制而来的一种制剂。由于传统栓剂无法持续恒定释药,且易受体温影响,融化后导致基质呈液状流出,污染衣物。复方替硝唑水凝胶栓是由替硝唑、醋酸氯己定、克霉唑与基质泊洛沙姆P407、卡波姆等辅料经先进工艺加工制成的白色透明胶冻状半固体水溶性凝胶,主要用于滴     

口服双氯芬酸钠pH敏感性水凝胶球研究

目的：以N-琥珀酰壳聚糖、海藻酸钠为载体,制备口服双氯芬酸钠pH敏感性水凝胶小球,并考察该水凝胶小球在不同pH环境中的释放行为。方法：通过正交试验优选口服双氯芬酸钠pH敏感性水凝胶小球最佳制备工艺。采用红外光谱和电子显微镜扫描对其进行结构表征,并考察该水凝胶小球在体外不同pH环境、人工胃液及人工肠液中的释放行为,揭示其在体外不同环境中的pH敏感性释放机制。结果：该水凝胶小球最佳处方组成为：N-琥珀酰壳聚糖浓度为1％(w/v),海藻酸钠浓度为1％(w/v),氯化钙浓度为1.5％(w/v),药物与海藻酸钠质量比为3∶5(g/g);口服双氯芬酸钠pH敏感性水凝胶小球具有明显的pH敏感性,在人工胃液中3 h的累积释放度小于22%,在人工肠液中11 h的累积释放度可达98%。结论：口服双氯芬酸钠pH敏感性水凝胶小球可望成为具有时辰药理学特性的pH敏感性肠道释药系统。     

两亲性PCL-PVP聚合物水凝胶负载布洛芬-精氨酸药物共晶制备及体外释放研究

目的：制备两亲性聚己内酯-聚乙烯吡咯烷酮（PCL-PVP）聚合物水凝胶用于负载布洛芬-精氨酸药物共晶并考察其体外释放行为。方法：采用溶剂挥发法制备物质的量比1：1布洛芬-精氨酸药物共晶;通过自由基溶液聚合法制备PCL-PVP聚合物凝胶。将布洛芬-精氨酸共晶负载于PCL-PVP聚合物凝胶上,考察不同亲疏水比例载药物共晶凝胶（PCL：PVP=1：9,3：7,5：5）在pH 5.8,7.4的PBS中的体外释放行为。结果：在pH 5.8 PBS中,布洛芬释放速率及释放量受载药凝胶亲疏水比例影响较大,释放72 h后, PCL：PVP=3：7的载药凝胶累积释放量达到约80%,为3组凝胶中的最大值。在pH 7.4 PBS中,不同亲疏水比例的载药凝胶的释放速率差别不大,布洛芬的释放速率较pH 5.8 PBS中的释放速率明显增大,在释放开始12 h后三者累积释放率均已接近或超过80%。结论：药物共晶的体外释放受多种因素影响,两亲性PCL-PVP聚合物凝胶可用于布洛芬-精氨酸药物共晶的载体,具有一定控释作用。     

盐酸拉莫三嗪纳米水凝胶的制备及其体外释放性能

目的 制备盐酸拉莫三嗪纳米水凝胶,并评价其体外释放性能.方法 采用无皂乳液共聚法制备纳米水凝胶,通过黏度仪、激光粒度和电位分析仪分别考察纳米水凝胶的黏度、粒径、电导率和溶胀率.利用纳米凝胶包载盐酸拉莫三嗪制得盐酸拉莫三嗪水凝胶,考察其体外释放性能.结果 最佳纳米水凝胶处方为甲基丙烯酸二甲氨基乙酯9.3 g,苯乙烯0.3...     

克林霉素磷酸酯聚氨酯水凝胶栓剂的制备及体外释放

目的：制备一种基于聚氨酯水凝胶的克林霉素磷酸酯缓释栓剂,并考察栓剂的体外释放及其影响因素。方法：以聚乙二醇6000、二环己基甲烷二异氰酸酯及1,2,6-己三醇为原料,采用一步法合成聚氨酯水凝胶材料,并通过傅里叶变换红外光谱及溶胀率对其进行初步表征。将聚氨酯水凝胶制成特定形状的空白栓剂,载入克林霉素磷酸酯后考察所得载药栓剂的体外释放行为,并探讨聚氨酯的化学组成、栓剂厚度、栓剂载药量及释放介质pH对载药栓剂体外释放的影响。通过Ritger—Peppas方程对释放数据进行拟合,探讨栓剂的释放机制。结果：合成了4批不同化学组成的聚氨酯水凝胶材料,其结构经FTIR确证,溶胀率则随交联率的增加而逐渐降低。制备的栓剂中克林霉素磷酸酯占目标载药量的103．0％（RSD=1．8％,／1,=10）。体外释放结果显示聚氨酯的化学组成及栓剂载药量对释放基本无影响;释放介质pH的升高及栓剂厚度的增加会减缓药物释放。释放数据分析结果表明克林霉素磷酸酯的释放由溶胀及扩散双重机制控制。结论：基于聚氨酯水凝胶的克林霉素磷酸酯栓剂制备方法简单、可控,体外释放完全,具有良好的应用前景。     

加替沙星pH敏感眼用原位凝胶体外释放的研究

目的研究加替沙星pH敏感眼用原位凝胶的体外释药特性与机制。方法采用改良桨法考察加替沙星pH敏感眼用原位凝胶的释药规律,并用无膜溶出法研究其释放机制。结果凝胶溶蚀和药物释放随着振荡频率和释放面积的增加而加快。其溶蚀度与释放度有明显相关性。结论体外的溶蚀行为与释放行为遵循零级动力学方程,凝胶溶蚀是决定药物释放的主要因素。     

灯盏花素微乳凝胶剂的体外释放度考察

目的 考察灯盏花素微乳凝胶剂体外释放度。方法 以pH 6.8的磷酸盐缓冲溶液为释放介质,分别采用正向透析扩散法和反向透析扩散法进行药物体外释放度试验。结果 采用反向透析扩散法测得的药物释放速率显著高于正向透析扩散法,采用反向透析扩散法时灯盏花素微乳凝胶剂在2 h内的累积释放量>60%,10 h的累积释放量>90%,其体外释药符合一级动力学方程。结论 采用反向透析扩散法方便快捷,能较好地模拟灯盏花素微乳凝胶剂的释药行为,灯盏花素微乳凝胶剂体外释药性能良好。     

盐酸左氧氟沙星凝胶剂的体外释放度考察

目的：探讨盐酸左氧氟沙星凝胶剂的体外释放度及释放动力学。方法：采用HPLC法测定释放介质中盐酸左氧氟沙星的含量,以此为指标,采用透析法研究凝胶与乳膏的体外释药特性。结果：凝胶剂中盐酸左氧氟沙星在36h已基本全部释放,释放过程以Weibull模型拟合最佳。与乳膏剂比较,释放速率快,释放完全。结论：盐酸左氧氟沙星制成凝胶剂后,具有速释作用,考察方法稳定、可靠。     

Controlled release of terbinafine hydrochloride from pH sensitive poly(acrylamide/maleic acid) hydrogels

Adsorption and controlled release of terbinafine hydrochloride (TER-HCl) to and from pH sensitive poly(acrylamide/maleic acid) (P(AAm/MA)) hydrogels were investigated. P(AAm/MA) hydrogels were prepared by irradiating the ternary mixtures of AAm/MA/and water by gamma-rays at ambient temperature. Antifungal drug, TER-HCl containing hydrogels, at different drug to polymer ratios, was prepared by direct adsorption method. The influence of MA content in the gel on the adsorption capacities of hydrogel and the effect of pH on the releasing behavior of TER-HCl from gel matrix were investigated. Terbinafine adsorption capacity of hydrogels are found to increase from 2 to 38 mg TER-HCl per g dry gel with increasing amount of MA in the gel system. In vitro drug release studies in different buffer solutions show that the basic parameters affecting the drug release behavior of hydrogel are the pH of the solution and MA content of hydrogel.     

高乌甲素脂质体凝胶制备工艺及体外释药性能研究

目的：制备高乌甲素脂质体（LA-LIP）经皮给药制剂,对其质量及透皮吸收性质进行考察。方法：采用薄膜分散法制备LA-LIP,以包封率与载药量为指标,运用正交试验法确定LA-LIP的优选处方;以卡波姆-940为基质制备LA-LIP凝胶,采用体外释放试验评估释放能力。结果：正交试验法确定LA-LIP最佳处方工艺组合为卵磷脂与胆固醇质量比为8：1、药脂比为1：8、水化温度为55℃。体外透析袋实验显示,LA-LIP凝胶慢释过程符合Higuchi方程,LA凝胶释放过程符合零级动力学方程;体外透皮结果显示,LA凝胶24 h内皮肤滞留量为8.39 μg·cm^-2,LA-LIP凝胶皮肤滞留量为15.17 μg·cm^-2。结论：本研究发现运用薄膜分散法制备LA-LIP工艺简单可靠,制备成脂质体凝胶剂时,具有缓释效果。     

嵌段共聚物OSM1-PCLA-PEG-PCLA-OSM1的pH和温度敏感性质及体外释药特性考察

目的 为嵌段共聚物磺胺甲嘧啶低聚物-聚-ε-己内酯-丙交酯-聚乙二醇-聚-ε-己内酯-丙交酯-磺胺甲嘧啶低聚物(sulfamerazine oligomers-poly(ε-caprolactone-co-DL-lactide-b-ethyleneglycol-b-ε-caprolactone-co-DL-lactide)-sulfamerazine oligomers,OSM1-PCLA-PEG-PCLA-OSM1)作为缓控释给药系统的载体提供依据.方法 采用激光粒度仪对不同pH和温度下嵌段共聚物OSM1-PCLA-PEG-PCLA-OSM1胶束粒径大小、分布进行考察;通过表面张力和相转变温度测定对其临界胶束浓度和溶液-凝胶相转变行为进行考察;以5 -氟尿嘧啶为模型药,通过透射电镜观察载药和空白共聚物胶束形态;采用物理混合法制备5 -氟尿嘧啶载药水凝胶;采用HPLC法测定载药水凝胶中药物释放速率.结果 嵌段共聚物OSM1-PCLA-PEG-PCLA-OSM1胶束溶液具有pH和温度双重敏感的性质,在一定pH和温度条件下可发生溶液-凝胶相转变;5 -氟尿嘧啶载药水凝胶体外释放可持续9 d,具有较好的缓释作用.结论 pH和温度双重敏感型嵌段共聚物OSM1-PCLA-PEG-PCLA-OSM1作为注射缓释给药系统载体材料具有良好的应用前景.     

In vitro dissolution of pH sensitive microparticles for colon-specific drug delivery

Objective: The objective of this work is to prepare oral dosage systems based on enteric materials in order to verify their possible use as Colon-Specific Drug Delivery Systems (CSDDSs).

Methodology: In particular, three different copolymers of methyl-methacrylate (MMA) - acrylic acid (AA) are synthesized with increasing percentage of MMA (from 70% to 73%) and they are used to produce microparticles by the double-emulsion solvent evaporation method. The microparticles, loaded using theophylline as model drug, are then tested for drug release under varying pH to reproduce what happens in the human GI tract.

Results: All the investigated systems have shown an effective pH sensitiveness: they show a good gastro-resistance, releasing the model drug only at higher pH, small intestine or colon, depending on the kind of used copolymer.

Conclusion: The results confirm the usefulness of both the materials and the methods proposed in this study for colon-specific delivery applications.     

An investigation into the influence of hydrogel composition on swelling behavior and drug release from poly(acrylamide-co-itaconic acid) hydrogels in various media

The hydrogels prepared by free radical copolymerization of acrylamide and itaconic acid were investigated with regard to their composition and crosslinking degree to find materials with satisfactory swelling and drug release properties. Samples were characterized by measuring the swelling behavior and in vitro release of paracetamol as a model drug in aqueous media with different pH values. The two-factor, three-level experimental design and response surface methodology were applied to statistically evaluate the influence of investigated factors.     

Pulsatile drug release control using hydrogels.

Current research in the field of drug delivery devices, by which pulsed and/or pulsatile release is achieved, has been intensified. In this article several types of drug delivery systems using hydrogels are discussed that showed pulsed and/or pulsatile drug delivery characteristics. As is frequently found in the living body, many vital functions are regulated by pulsed or transient release of bioactive substances at a specific site and time. Thus it is important to develop new drug delivery devices to achieve pulsed delivery of a certain amount of drugs in order to mimic the function of the living systems, while minimizing undesired side effects. Special attention has been given to the thermally responsive poly(N-isopropylacrylamide) and its derivative hydrogels. Thermal stimuli-regulated pulsed drug release is established through the design of drug delivery devices, hydrogels, and micelles. Development of modified alginate gel beads with pulsed drug delivery characteristic is also described in this article.     

药物导电压敏胶的制备及其体外透皮释放试验

目的:考察固化在导电压敏胶中的吲哚美辛在低频脉冲电流作用下的释放现象,试图将透皮给药治疗体系与低频脉冲电刺激相结合来提高疗效。方法:利用紫外光固化技术将吲哚美辛直接固化在导电压敏胶中,通过药物体外透皮释放模型测定吲哚美辛的释放。结果:光引发剂对压敏胶固化有重要影响,使用混合光引发剂有利于固化;压敏胶厚度不宜超过2cm;吲哚美辛药量增加,对预聚体配方的固化及保存有影响,吲哚美辛合适用量约为0.50％。结论:制得了固化良好、具有一定粘性和可多次使用的含药导电压敏胶;低频脉冲电流刺激下(正、负极),压敏胶中吲哚美辛的释放加快。     

莫达非尼肠溶片体外释放度的研究

莫达非尼（modafinil）是一种新型非苯丙胺类中枢神经系统兴奋药，化学名称2-（二苯甲基亚硫酰）乙酰胺，该药略溶于甲醇，在乙醇或乙酸乙酯中做溶，几乎不溶于水，它具有良好的中枢兴奋作用，能改善因长期睡眠剥夺（sleep deprivation，SD）导致人体疲劳困倦程度增加．以及由认知能力下降产生的不良影响。临床用于治疗发作性睡病。改善病人白天嗜睡症状，维持正常工作，却不会出现异常兴奋。有研究认为合理使刖该药是提高部队战斗力和持续作战能力，     

嵌段共聚物OSM1-PCLA-PEG-PCLA-OSM1的pH和温度敏感性质及体外释药特性考察

目的 为嵌段共聚物磺胺甲嘧啶低聚物-聚-ε-己内酯-丙交酯-聚乙二醇-聚-ε-己内酯-丙交酯-磺胺甲嘧啶低聚物（sulfamerazine oligomers-poly(ε-caprolactone-co-DL-lactide-b-ethyleneglycol-b-ε-caprolactone-co-DL-lactide)-sulfamerazine oligomers,OSM₁-PCLA-PEG-PCLA-OSM1)作为缓控释给药系统的载体提供依据。方法 采用激光粒度仪对不同pH和温度下嵌段共聚物OSM₁-PCLA-PEG-PCLA-OSM₁胶束粒径大小、分布进行考察;通过表面张力和相转变温度测定对其临界胶束浓度和溶液-凝胶相转变行为进行考察;以5-氟尿嘧啶为模型药,通过透射电镜观察载药和空白共聚物胶束形态;采用物理混合法制备5-氟尿嘧啶载药水凝胶;采用HPLC法测定载药水凝胶中药物释放速率。结果 嵌段共聚物OSM₁-PCLA-PEG-PCLA-OSM₁胶束溶液具有pH和温度双重敏感的性质,在一定pH和温度条件下可发生溶液-凝胶相转变;5-氟尿嘧啶载药水凝胶体外释放可持续9 d,具有较好的缓释作用。结论 pH和温度双重敏感型嵌段共聚物OSM₁-PCLA-PEG-PCLA-OSM₁作为注射缓释给药系统载体材料具有良好的应用前景。     

In vitro drug release mechanism from lipid nanocapsules (LNC)

Lipid nanocapsules are recently developed lipid nanocarriers for delivery of lipophilic drugs. Due to their small size and biocompatible nature, lipid nanocapsules (LNC) may be promising carriers for drug delivery with different routes of administration. The aim of this work was to study the effect of formulation variables on the in vitro drug release from LNC. Ibuprofen as a model drug was entrapped in the oily core while Cremophor A25 and Cremophor A6 were used as hydrophilic surfactants in different ratios ranging from 1:1 to 1:0. All the prepared LNC were of comparable particle sizes around 50 nm. Varying Cremophor compositions as well as the presence of lecithin, cetyl or stearyl alcohol had no significant effect on the in vitro drug release profiles. However, drug release rates increased significantly with increasing the temperature from 4 to 50 °C, i.e. the flux increased from 1.5 to 7 μg/(cm² min). This was explained by the increased ibuprofen–lipid interactions at reduced temperature where the increased viscosity of the lipid significantly slows down the drug diffusion to the external aqueous phase. In summary, the physicochemical properties of the drug as well as the oil phase have a high impact on the drug release rate while the surfactant type, composition or density exerted only a minor effect.