海藻酸钙凝胶微球的制备和pH依赖性溶胀

利用海藻酸钠溶液与氯化钙溶液发生胶凝反应，本文用滴制的方法制备了海藻酸钙凝胶微球，并对制备的处方和工艺进行了探讨，同时考察了海藻酸钙凝胶微球的特征和溶胀特性。干燥的凝胶微球在不同pH的水性介质中溶胀特性不同。海藻酸钙凝胶微球的这种溶胀的pH敏感性，使其能成为口服药物缓释制剂的载体。     

硝苯地平海藻酸钙凝胶缓释微丸处方及工艺的优化

目的制备硝苯地平 海藻酸钙凝胶缓释微丸。方法采用滴制法。用单因素考察及均匀设计实验优化处方及工艺。结果优化得到的微丸在体外累计释放硝苯地平百分率 ,2h为 2 0 %～ 3 0 % ,6h为 60 %～ 80 % ,1 2h>85 %。结论在体外释放度实验中 ,硝苯地平海藻酸钙凝胶微丸具有良好的缓释作用     

阿霉素海藻酸钙凝胶微丸的释放性

以阿霉素为阳离子模型药物，研究了不同初始浓度海藻酸钠（ＳｏｄｉｕｍＡｌｇｉｎａｔｅ，ＮａＡｌｇ）制备的空白微丸对药物的摄取作用和不同介质中药物的释放过程     

阿西美辛海藻酸钙凝胶微丸释药影响因素考察

目的:考察阿西美辛海藻酸钙凝胶微丸的释药机制。方法:采用滴制法制备阿西美辛海藻酸钙微丸,考察海藻酸钠浓度,钙离子浓度,投药量,滴头直径大小对药物释放的影响。结果:海藻酸钠浓度增加,钙离子浓度增加,滴头直径增加,释药速率减慢。结论:在体外释放度实验中,阿西美辛海藻酸钙凝胶微丸具有良好的缓释作用,海藻酸钙凝胶微丸是一种非常有潜力的药物载体。     

海藻酸钙凝胶微球中模型药物的pH值依赖性释放

目的:考察海藻酸钙凝胶微球中模型药物的pH值依赖性释放.方法:以硝苯地平为模型药,采用滴制法制备了含药微球;考察了含药微球在不同pH值介质中的释放特性.结果:含药微球在水及pH 1.0的介质中几乎不溶胀,12 h累积释放百分率为23.1%和23.4%;在pH6.8的介质中微球溶胀至完全溶蚀,且呈现缓慢释放的趋势,12 h药物的累积释放百分率为92.5%;换介质的释放中,0～2 h微球几乎不溶胀,2 h累积释放8.4%,介质pH改变后微球很快崩解,3 h累积释放82.4%.结论:海藻酸钙凝胶微球中硝苯地平的释放具有pH值依赖性,在pH 6.8的介质中缓释.     

双氯芬酸钠海藻酸钙凝胶微球的制备及其性质分析

目的制备双氯芬酸钠海藻酸钙凝胶微球，并对凝胶微球的性质进行分析。方法采用滴制法制备双氯芬酸钠海藻酸钙凝胶微球，紫外分光光度法测定药物的含量，对凝胶微球的粒度、圆整度、休止角和堆密度进行测定，并用扫描电镜观察凝胶微球的形态。结果制备的双氯芬酸钠海藻酸钙凝胶微球包封率较高，粉体学性质良好，球形均匀圆整。结论该方法适用于双氯芬酸钠海藻酸钙凝胶微球的制备。     

萘普生海藻酸钙凝胶微丸的制备及体外释药

目的：制备萘普生海藻酸钙凝胶微丸，并建立其释放度测定方法。方法：采用均匀设计优化处方，用分光光度法测定萘普生的含量，用体外溶出实验考察其释放效果。结果：在优化条件下制备的凝胶微丸外观好，载药量（62．2±1．8）％，在模拟胃液（SGF）中2h释放率小于3．1％，在模拟肠液（SIF）中45min释放达95％以上。结论：在优化条件下可制备外观好，载药量高的萘普生海藻酸钙凝胶微丸，体外溶出符合肠溶特征。     

不透X线标志物硫酸钡海藻酸钙微丸的研制

目的：制备硫酸钡海藻酸钙微丸作为不透X线标志物用于结肠传输功能检查。方法：采用滴制法制备硫酸钡海藻酸钙微丸,以微丸圆整度、脆碎度、粒径分布为质量指标,通过正交试验选出优化处方及工艺,并以乙基纤维素为包衣材料,用底喷式流化床悬浮包衣法进行包衣。结果：所制得的硫酸钡海藻酸钙微丸抗腐蚀性强,在胃肠中稳定,且显影清晰。结论：硫酸钡海藻酸钙微丸制备方法简便,成本低,材料易得,符合结肠传输功能检查的基本要求。     

硝苯地平缓释微丸的研制

用滚动凝聚法制备硝苯地平缓释微丸,微丸中硝苯地平体外释药前段呈零级,后段符合Ｈｉｇｕｃｈｉ方程,持续释药时间达８ｈ。     

酮洛芬果胶钙凝胶小球和海藻酸钙凝胶小球的制备及性能比较

目的酮洛芬果胶钙凝胶小球和酮洛芬海藻酸钙凝胶小球的制备及性能比较。方法利用果胶、海藻酸钠及二者不同比例,以酮洛芬为模型药物采用滴制法制备凝胶小球,考察2种多糖物质对药物包封率和释放行为的影响。利用大鼠肠囊外翻实验对凝胶小球的生物黏附性能进行比较,通过对释放机理的探讨和凝胶小球溶胀性的测定进一步证明2种凝胶小球释药行为的不同。结果酮洛芬果胶钙凝胶小球和酮洛芬海藻酸钙凝胶小球均具有良好的生物黏附性能,果胶钙凝胶小球主要通过溶胀作用缓慢释药,而海藻酸钙凝胶小球的释药与凝胶小球慢慢吸水后骨架溶蚀有关。结论酮洛芬果胶钙凝胶小球和酮洛芬海藻酸钙凝胶小球通过与生物黏膜的紧密结合缓慢释药,而二者的释放行为有所不同。     

Morphology and buoyancy of oil-entrapped calcium pectinate gel beads

A new emulsion-gelation method to prepare oil-entrapped calcium pectinate gel (CaPG) beads capable of floating in the gastric condition was designed and tested. The gel beads containing edible oil were prepared by either being gently mixed or homogenized an oil phase and a water phase containing pectin, and then extruded into calcium chloride solution with gentle agitation at room temperature. The gel beads formed were then separated, washed with distilled water, and dried at 37 degrees C for 12 hours. A model of the emulsion-gelation process to illustrate the formation of oil-entrapped CaPG beads was proposed. The effect of selected factors, such as type of oil, percentage of oil, and type of pectin on morphology and floating properties was investigated. The oil-entrapped calcium pectinate gel beads floated if a sufficient amount of oil was used. Scanning electron photomicrographs demonstrated very small pores, ranging between 5 and 40 microm, dispersed all over the beads. The type and percentage of oil play an important role in controlling the floating of oil-entrapped CaPG beads. The results suggested that oil-entrapped CaPG beads were promising as a carrier for intragastric floating drug delivery.     

Development and evaluation of polyethyleneimine-treated calcium alginate beads for sustained release of diltiazem

The objective of this investigation is to develop a multi-unit sustained release dosage form of a water soluble drug from a completely aqueous environment avoiding the use of any organic solvent. The drug was complexed with resin and calcium alginate or polyethyleneimine-treated calcium alginate beads loaded with the resinate were prepared by a ionic/polyelectrolyte complexation method. The effect of different formulation variables on the characteristics of the beads was investigated. Although the drug release from spherical and smooth-surfaced calcium alginate beads in both acidic and alkaline dissolution media were slower than those obtained from plain resinate, none of the variables were found to prolong the drug release considerably due to rapid swelling and disintegration of calcium alginate beads in alkaline medium. On the other hand, drug release from polyethyleneimine-treated calcium alginate beads in acidic medium did not increase appreciably following a burst release. However, in alkaline medium, the drug release was found to increase gradually and extend over a different period of time depending on the intensity of polyethyleneimine treatment. Scanning electron micrographs revealed the formation of a dense membrane around the resinate-loaded calcium alginate matrix. The membrane appeared to be responsible for reduced swelling and protracted disintegration of the beads resulting in slow release of the drug. The results indicate that sustained release of a water soluble drug from polyethyleneimine-treated calcium alginate beads could be achieved by adjusting the formulation variables.     

双嘧达莫胃漂浮缓释微丸的研究

目的结合固体分散技术制备双嘧达莫的褐藻酸钙-壳聚糖胃漂浮型缓释微丸(Dip-Ca-alg-cs-beads),对其漂浮性能,包封率,体外释药性能进行考察。方法以乙基纤维素,聚丙烯酸树脂II和Eudragit RLPO为联合载体制备双嘧达莫固体分散体,粉碎后分散于添加制泡剂的褐藻酸钠溶液中,并缓慢滴入添加醋酸的壳聚糖-氯化钙溶液中反应固化,干燥后得到胃漂浮缓释微丸。考察固体分散体对微丸体外释药的影响。结果通过调节配方,微丸在人工胃液中12 h漂浮率大于90%。双嘧达莫6 h释放65%~70%,包封率85%~90%。结论运用固体分散技术可实现双嘧达莫在褐藻酸钙-壳聚糖胃漂浮微丸(Ca-alg-cs-beads)中的缓释,并为这类药物的多单元胃漂浮给药系统的发展提供了思路。     

Biphasic release characteristics of dual drug-loaded alginate beads

The dual drug-loaded alginate beads simultaneously containing drug in inner and outer layers were prepared by dropping plain (single-layered) alginate beads into CaCl₂ solution. The release characteristics were evaluated in simulated gastric fluid for 2 h followed by intestinal fluids thereafter for 12 h. The surface morphology and cross section of dual drug-loaded alginate beads was also investigated using scanning electron microscope (SEM). The poorly water-soluble ibuprofen was chosen as a model drug. The surface of single-layered and dual drug-loaded alginate beads showed very crude and roughness, showing aggregated particles, surface cracks and rough crystals. The thickness of dual drug-loaded alginate beads surrounded by outer layer was ranged from about 57 to 329μm. The distinct chasm between inner and outer layers was also observed. In case of single-layered alginate beads, the drug was not released in gastric fluid but was largely released in intestinal fluid. However, the release rate decreased as the reinforcing Eudragit^® polymer contents increased. When the plasticizers were added into polymer, the release rate largely decreased. The release rate of dual drug-loaded alginate beads was stable in gastric fluid for 2 h but largely increased when switched in intestinal fluid. The drug linearly released for 4 h followed by another linear release thereafter, showing a distinct biphasic release characteristics. There was a difference in the release profiles between single-layered and dual drug-loaded alginate beads due to their structural shape. However, this biphasic release profiles were modified by varying formulation compositions of inner and outer layer of alginate beads. The release rate of dual drug-loaded alginate beads slightly decreased when the outer layer was reinforced with Eudragit^® RS100 polymers. In case of dual drug-loaded alginate beads with polymer-reinforced outer layer only, the initial amount of drug released was low but the initial release rate (slope) was higher due to more swellable inner cores when compared to polymer-reinforced inner cores. The current dual drug-loaded alginate beads may be used to deliver the drugs in a time dependent manner.     

Evaluation of drug release kinetics and physico-chemical characteristics of metronidazole floating beads based on calcium silicate and gas-forming agents

In the present investigation metronidazole-loaded alginate beads consisting of calcium silicate as a porous carrier or NaHCO₃ as a gas-forming agent were prepared for local eradication of Helicobacter Pylori. Gelation method was used for preparation of conventional sodium alginate beads. Drug entrapment efficiency, drug loading, floating properties, drug release, crystallinity and release kinetic as well as morphology of the prepared beads were assessed. The silicate based beads showed slower release pattern, compared to the gas-forming beads due to network structure strengthening effect of the calcium silicate. Furthermore, the gas-forming-based beads had shorter initial buoyancy lag time, owing to the fact that the NaHCO₃ produced larger pores than those of silicate treated ones. Drug entrapment efficiency ranged between 61.7 and 93.1% for the prepared formulations. The maximum value of drug loading for gas-forming and silicate-based beads were 66.64% and 34.97%, respectively. Kinetically, release pattern of metronidazole in simulated gastric fluid from the beads fitted best to Reciprocal powered time, Weibull and log-probability models with the respect overall mean percentage error values of 4.50, 5.30 and 7.76. By and large, these systems can float in the gastric condition and control the drug release from the beads.