难溶性药物渗透泵制剂制备工艺的研究进展

目的:综述难溶性药物渗透泵制剂制备工艺的研究进展。方法:查阅2003-01-01至2013-04-30国内外涉及难溶性药物渗透泵制剂制备的相关文献,从增加药物溶解度、增强机械穿透系数、增大渗透压差3个方面总结了制备工艺的研究进展。结果与结论:增加药物溶解度可以通过加入β-环糊精、酸碱性物质、制备泡腾渗透泵片等方式实现;增强机械穿透系数可通过采用不对称膜、制备微孔渗透泵等方式实现;增大渗透压差可通过制备单层高分子、双层、三层渗透泵片或者双室渗透泵片来实现。随着新辅料和新技术的应用,难溶性药物特别是治疗指数低、半衰期短的药物制备成渗透泵制剂的工艺将不断创新。     

将难溶性药物制成单层渗透泵片的中间技术-固体分散体技术

对于难溶性药物而言,不能像水溶性药物一样,按照普通的方法制成释药完全的单层渗透泵片。本论文主要介绍通过固体分散体技术提高难溶性药物的溶解度,再制备成单层渗透泵制剂,进而提高药物的溶解度及其体内生物利用度。     

难溶性药物口服渗透泵片工艺的研究进展

在控释制剂中 ,口服渗透泵最理想。它可避免普通口服制剂应用造成的血药浓度波动较大的现象 ,减少用药次数与全身副作用 ,提高药物的安全性和有效性 ,且释药速度不受胃肠道 ｐＨ值影响及个体差异的影响较小。渗透泵制剂的研究始于 1955年。随着药剂学理论和科学技术的发展 ,1973年Ｈｉｇｕｃｈｉ设计并申请了渗透泵专利。而Ｔｈｅｅｕｗｅｓ[1]1975年发表的有关渗透泵的基本理论 ,则奠定了渗透泵制剂在控释制剂中的特殊地位。目前开发的制剂以水溶性药物为主 ,这主要和渗透泵的释药原理有关。但如果将治疗指数小的难溶性药物制备成渗透泵 ,…     

难溶性药物单层渗透泵片制备工艺的研究进展

将难溶性药物制成单层渗透泵给药系统,本文通过对近年来有关难溶性药物渗透泵给药系统的制备工艺进行概述总结.     

不同溶解性药物口服渗透泵片片芯的处方设计

目的:综述渗透泵片片芯的处方设计.方法:通过文献检索进行归纳总结.结果:从药物溶解度出发,详细论述了水难溶性药物、中等水溶性药物以及易溶于水的药物在制成口服渗透泵片的过程中需要注意的问题及其解决方法.结论:采取不同的制剂手段可实现各种不同溶解性药物的控制释放.     

丙烯酸树脂RS100和丙烯酸树脂RL100混合包衣制备法莫替丁渗透泵控释片

目的制备难溶性药物法莫替丁渗透泵型控释片,并考察其释药的影响因素,探讨药物释药规律。方法从渗透促进剂用量、阿拉伯胶用量、衣膜性质、释药孔径和转速等5个因素考察对释药的影响。结果制备了难溶性药物法莫替丁渗透泵型控释片,氯化钠、阿拉伯树脂胶、衣膜厚度是影响释药的主要因素。结论法莫替丁渗透泵型控释片工艺稳定,能够达到12 h明显的恒速释药。     

渗透泵制剂的研究进展

从渗透泵的构成和释药原理入手，着重讨论其对药物水溶性的要求，乳胶包衣膜的致孔和各种类型的渗透泵剂型。列出了已上市和待上市的口服渗透泵品种。渗透泵控释制剂具有很好的前景。国内应大力研究开发，争取早日应用。     

尼莫地平渗透泵型控释片的研制及释药影响因素考察

目的制备中剂量难溶性药物尼莫地平单室渗透泵型控释片 ,并考察其释药机理及影响释药因素 ,探讨药物释药规律。方法单因素考察影响释药的因素。结果制备了中剂量难溶性药物尼莫地平单室渗透泵型控释片 ;氯化钠、阿拉伯树脂胶、衣膜厚度及增塑剂的用量是影响释药的主要因素。结论尼莫地平单室渗透泵型控释片工艺稳定 ,能够达到 12h明显的恒速释药     

长春西汀双层渗透泵控释片的制备及体外释放度考察

目的制备难溶性药物长春西汀单室双层渗透泵控释片,并对其体外释药影响因素进行考察。方法利用正交设计优化了渗透泵处方,根据不同时间累积释放度对药物的释放情况进行了考察。结果渗透泵控释片的最优处方为长春西汀15 mg、HPMC 140 mg、PEO 65 mg、氯化钠14 mg,包衣增质量24 mg。其体外释药特征符合控释制剂的要求。结论本渗透泵片以渗透压差为释药动力,能在14 h内良好的控制长春西汀零级释放。     

渗透泵制剂的研究进展

从渗透泵的构成和释药原理入手,着重讨论其对药物水溶性的要求、乳胶包衣膜的致孔和各种类型的渗透泵剂型。列出了已上市和待上市的口服渗透泵品种。渗透泵控释制剂具有很好的前景,国内应大力研究开发,争取早日应用。     

A novel solubility-modulated granules through porosity osmotic pump for controlled carvedilol delivery

A method for the preparation of porosity osmotic pump granules was obtained by modulating carvedilol solubility with tartaric acid. Controlled porosity of the membrane was accomplished by the use of pore-forming agent in the coating. In this study, carvedilol was chosen as a model drug with an aim to develop a zero-order release system; tartaric acid was used as the solubility promoter; NaCl was used as the osmotic agent; cellulose acetate (CA) was used as the materials of semipermeable membrane; and PEG-400 was used as the pore-forming agent in the semipermeable membrane. The influence of different factors or levels on the in vitro release was studied. In order to simulate the gastrointestinal tract environments, two kinds of pH media (pH 1.5 and 6.8) on drug release were studied in this research, respectively. This porosity osmotic pump was optimized by single factor design experiments, and it was found to deliver carvedilol at a zero-order rate within 12?h and controlled release for 24?h. We drew a conclusion that the solubility-modulated porosity osmotic pump system is simple to prepare and might be used for the preparation of osmotic pump system of other poorly water-soluble drugs with alkaline or acid groups.     

岩白菜素包合物渗透泵片制备工艺研究

目的利用β-环糊精（β-CD）包合技术改善微溶性药物岩白菜素的体外溶出行为,进而考察片芯及包衣处方对岩白菜素包合物渗透泵片体外释药性质的影响,并优选最佳片芯及包衣处方。方法采用饱和水溶液法制备岩白菜素β-CD包合物,并测定其溶出速率和溶解度;根据不同时间的累积释放度,考察药物的释放情况,通过单因素考察及正交试验设计优化片芯及包衣处方。结果聚氧乙烯的分子量和用量及甘露醇的用量,对岩白菜素包合物渗透泵片体外释药行为有影响。最后所得处方可在12h内稳定释药且累积释放度可达到90%以上。结论以岩白菜素β-CD包合物为中间体,可以制成零级释药特征显著的单室单层渗透泵片。     

Development of ALZET® osmotic pump compatible solvent compositions to solubilize poorly soluble compounds for preclinical studies

Context: Hydrophilic, non-aqueous solvents are frequently used to solubilize poorly water soluble compounds for use in ALZET^® osmotic pumps used during the discovery and preclinical stages. Though these solvents exhibit the potential to solubilize several poorly soluble compounds, the solubilized compounds are prone to crystallization up on contact with aqueous fluids in vitro and in vivo. Crystallization of a compound can potentially cause pain at the release site, erratic blood levels, and uneven or delayed pharmacokinetic profiles.

Objective: In this study, we discussed the development of ALZET^® pump compatible hydrophilic, non-aqueous vehicles that solubilized two poorly soluble model compounds (ELND006 and ELN 481594) and prevented their crystallization from solutions in vitro and in vivo.

Methods: The selected formulations were filled into the pumps at three concentrations for each model compound and investigated for their compatibility with the pumps and the subcutaneous tissue of mice where the pump was inserted.

Results and Discussion: The results showed that the formulations were stable physically with no crystallization and chemically with no degradation and were compatible with the pump and animal tissue. The plasma concentration of ELND006 decreased with time at each dose. The extent of the time-dependent decrease in ELND006 plasma levels increased as the amount of dose delivered increased. This time and dose dependent decrease in ELND006 plasma concentrations was attributed to the known auto-induction of hepatic enzymes by the compound. In contrast, the plasma concentration of ELN 481594 increased significantly at higher dose, likely due to accumulation of the compound.     

复方二甲双胍/格列吡嗪单室渗透泵片的释药机理

目的在以前的实验中研制了复方二甲双胍/格列吡嗪单室渗透泵片,但是其释药机理没有阐明。方法在本文中,主要考察了可能影响药物释放的三个限速因素(半透膜,片心和释药孔)。结果研究发现单位时间内透进渗透泵的水量同二甲双胍的释放速率基本相当,但远小于片心的溶出速率;孔径从0·4到0·8毫米对药物释放无显著影响;片心的渗透压主要由二甲双胍产生。结论从渗透泵系统的数学模型来看,主要限速步骤在于单位时间透过半透膜的水量,不是片心溶出速率和溶液从小孔的释放速率,片心的溶出速率同溶液从小孔的释放速率相等,因此渗透泵系统表现出零极释放。     

卡维地洛微孔渗透泵颗粒的制备及其性能

目的:制备卡维地洛微孔渗透泵颗粒,并对其性能进行研究。方法:以卡维地洛作为模型药物,以氯化钠为渗透压活性物质,酒石酸为溶解度调节剂,醋酸纤维素为包衣膜材,PEG400为水溶性致孔剂,采用正交试验设计法L9(34)优选卡维地洛微孔渗透泵颗粒制备工艺。结果:卡维地洛微孔渗透泵颗粒在模拟胃肠环境中按零级动力学方式释放药物,具有明显的渗透泵特征和控释效果,且基本不受胃肠pH环境的影响,12 h内累积释放度可达71.90%。结论:卡维地洛微孔渗透泵颗粒处方组成合理、制备工艺可行,可望成为一种新的卡维地洛控释剂型。     

酒石酸托特罗定渗透泵片的制备及释放度测定

目的制备酒石酸托特罗定渗透泵片,考察其体外释药特性。方法以阿拉伯胶和氯化钠为渗透活性物质制成片芯,以醋酸纤维素、邻苯二甲酸二丁酯和聚乙二醇400为包衣材料,丙酮为包衣溶剂,制备酒石酸托特罗定渗透泵片;采用高效液相色谱法测定其体外释放度。结果以单用阿拉伯胶为促渗剂,当主药与阿拉伯胶用量比为1∶25时,制得的酒石酸托特罗定渗透泵片10h内恒速释药,释药量达85%以上。结论本试验研制的酒石酸托特罗定渗透泵片释药恒速,制备简单,重现性好。     

特拉唑嗪单芯渗透泵片研制及其控制释放的因素

目的：研制难溶性药物特拉唑嗪的单芯渗透泵。方法：片芯中加入亲水性高分子，用乙基纤维素溶液包衣制备单尊渗透泵，并研究片芯处方、释药孔径等因素对释药行为的影响。结果：在0．80-1．15mm范围内，孔径对制备的渗透泵片释药行为没有影响，且自制渗透泵片在0～24h释放速度平稳，与胃肠道环境pH值和溶出仪转速无关。结论：制备的单芯渗透泵     

双室型渗透泵控释制剂的研究进展

对渗透泵式控释制剂的发展过程以及不同形式双室型渗透泵控释制剂的研究进展加以阐述 ,并针对目前广泛应用的带有可扩展渗透室的双室型渗透泵控释制剂进行了详细的介绍 .     

Design and Evaluation of Bilayer Pump Tablet of Flurbiprofen Solid Dispersion for Zero-Order Controlled Delivery

In this study, a bilayer osmotic pump tablet of flurbiprofen (FP) solid dispersions (SDs) was developed to increase the solubility of the poorly soluble drug and controlled drug release at a constant rate. Based on the investigation of thermodynamic properties the drug, the carrier, and the calculation of the solubility parameters, the FP-SD was prepared by hot-melt extrusion technique with the povidone (PVP) VA64 carrier. Then, central composite design-response surface methodology was used to evaluate the influence of factors on the responses. Consequently, PVP VA64 was selected as the carrier for preparing FP-SD. The results of differential scanning calorimetry and X-ray confirmed that FP in FP-SD was in an amorphous state. FTIR indicated that the intermolecular hydrogen bond probably formed between FP and PVP VA64 in FP-SD. Correlation of release profiles to zero-order kinetics was significant (R² = 0.9939). The mathematical models had good predictability because the deviation was less than 1% between the predicted value and measured value. These results demonstrated that FP-SD osmotic pump tablets successfully increased the solubility of FP and controlled the release of FP at a constant rate.