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。     

雷公藤胃漂浮缓释微丸的制备

目的:制备雷公藤胃漂浮缓释微丸,考察其漂浮和释药性能。方法:以微丸的体外释放度、漂浮性能为考察指标,采用挤出滚圆法制备胃漂浮空白微丸,采用流化床包衣设备依次进行载药层和缓释层包衣,制备雷公藤胃漂浮缓释微丸。结果:以90%十八醇为助漂剂,10%微晶纤维素为稀释剂制得空白胃漂浮微丸;以1%羟丙基甲基纤维素和0.5%十二烷基硫酸钠为载药层包衣材料,以含3%聚维酮的乙基纤维素水分散体为缓释层包衣材料。制得的雷公藤胃漂浮缓释微丸在人工胃液中立即起漂,8h漂浮率均>80%,体外释药机制符合一级释药方程。结论:所制雷公藤胃漂浮缓释微丸具有良好的漂浮性能和缓释特性。     

硝苯地平胃漂浮型延迟缓释微丸的制备

目的:制备硝苯地平胃漂浮型延迟缓释微丸并考察其体外漂浮行为.方法:挤出滚圆法制备漂浮型空白丸芯,空白丸芯上药法制备载药丸芯,分别以Surelease水分散体和Eudragit L30D-55为包衣材料,进行流化床包衣.采用正交试验设计对处方进行优化.结果:模拟人体胃肠道条件下溶出,自制漂浮型微丸在人工胃液中6 h累计释放小于10%,换人工肠液后12 h释放完全,体外漂浮10 h以上. 结论:自制微丸达到了漂浮和延迟缓释的效果.     

一种产气型胃漂浮微丸的制备及其漂浮性和体外释放度的考察

目的以法莫替丁为模型药物,制备一种胃漂浮微丸,以延长胃内存留时间,提高药物的生物利用度。方法采用挤出滚圆法制备载药丸芯,以粉体学性质为指标进行处方筛选;采用流化床包衣的方法在载药丸芯外部包上产气层(含有碳酸氢钠的羟丙基甲基纤维素)和阻滞层(EudragitRL30D,RS30D,NE30D),并分别考察各处方微丸的漂浮性和体外释放性质。结果制得的微丸可以在5 min内起漂,持续漂浮达8 h以上,药物5 h缓释率达到93.5%。微丸的起漂时间随着产气物质[碳酸氢钠(NaHCO3)]质量的增加而缩短,随着外层阻滞层包衣增量的增加(EudragitNE30D)或Eudragit RS30D质量的增加(Eudragit RL30D/RS30D)而延长。结论试验制得的胃漂浮型微丸既能快速起漂、持续漂浮达8 h以上,又能缓慢释放药物。     

氧氟沙星胃漂浮微丸的制备

目的制备以氧氟沙星为主药的胃漂浮缓释微丸。方法以微晶纤维素为骨架材料,采用挤出滚圆法制备氧氟沙星微丸。以Kollicoat SR30D为内层包衣材料(缓释层),碳酸氢钠为中间层(产气层),Eudragit RL30D为外层包衣材料(阻滞层)进行包衣,制成氧氟沙星胃漂浮微丸。通过星点设计-效应面优化法考察了胃漂浮微丸的处方,分别考察各处方微丸的漂浮性和体外释放性质。结果试验制得的胃漂浮微丸既能快速起漂、持续漂浮达8 h以上,又能达到2、4、8和24 h累计释放率分别为(32.37±0.88)%、(50.18±0.37)%、(69.36±0.89)%和(97.64±0.87)%的缓释效果。结论所制得的包衣微丸在人工胃液(p H=1.2)中具有良好的漂浮性能和缓释性能。     

双氯芬酸钠/海藻酸钠微球的制备与体外释药行为考察

目的以海藻酸钠为载体材料,双氯芬酸钠为模型药物,制备载药微球并考察其性质及体外释放行为。方法本文采用海藻酸钠为药物载体,采用喷雾干燥法制备双氯芬酸钠/海藻酸钠微球。考察于双氯芬酸钠/海藻酸钠投料比对载药微球理化性质的影响。采用扫描电镜对所得到的微球进行形貌观察。同时考察其体外药物释放行为。结果所得到的载药微球形态呈不规则的扁平状,粒径分布较为均匀。通过控制投料比,可以得到不同粒径(5.64～9.58μm),载药量(5.76～18.43%)和包封率(35.45～43.92%)的载药微球。体外药物释放行为结果显示微球在含有0.5%氯化钙的PBS(pH=7.4)溶液的药物释放时间可以持续96h,具有一定的缓释效果。结论通过喷雾干燥法制备的双氯芬酸钠/海藻酸钠载药微球具有较高载药量和一定的药物缓释效果。     

克拉霉素缓释包衣微丸的制备及体外释放度研究

目的制备克拉霉素缓释包衣微丸,并对其体外释放度进行考察。方法采用挤出滚圆技术制备克拉霉素含药微丸。以优化的丙烯酸树脂类Eudragit NE30D和Eudragit L30D-55混和水分散体为包衣材料,采用流化床包衣技术,制备缓释包衣微丸。考察自制缓释微丸的体外释药速率,并与市售的克拉霉素缓释胶囊进行比较。结果通过释药行为的评价,得到优化的包衣处方为5∶1的Eudragit NE30D和Eudragit L30D-55混和包衣材料,其体外释放行为在不同的pH溶出介质中与市售制剂产品没有明显差异,体外释药过程符合一级释放模型。结论采用挤出滚圆和流化床技术,以及优化的Eudragit NE30D和Eudragit L30D-55混和水分散体包衣材料,成功制备了克拉霉素缓释包衣微丸。     

酒石酸美托洛尔延迟起释缓释微丸的制备

目的制备酒石酸美托洛尔延迟起释缓释微丸;研究该制剂的体外释放影响因素。方法采用挤出滚圆法制备含药丸芯,以丙烯酸树脂(Eudragit NE 30D)为内层包衣材料,乙基纤维素与丙烯酸树脂(Eudragit L100)的混合膜材为外层包衣材料制备延迟起释缓释微丸。通过改变内层包衣质量增加、外层包衣质量增加及外层包衣液中乙基纤维素与Eudragit L 100的质量比来达到一定时滞后缓慢释放药物的目的。考察了处方因素和溶出条件对体外释放度的影响。结果制得时滞为4 h,4、6、10、14 h的累积释放量分别为<10%、20%~35%、50%~70%、≥75%的延迟起释缓释微丸。结论内层包衣质量增加、外层包衣液中乙基纤维素与Eudragit L100的比例及外层包衣质量增加对延迟起释缓释微丸的释药时滞和释药速率具有显著影响,药物的体外释放情况不受溶出转速和溶出装置的影响。     

法莫替丁胃漂浮微丸的制备及质量评价

目的制备法莫替丁为主药的胃漂浮缓释微丸,并对其做质量评价。方法以微晶纤维素和十八醇为骨架材料,采用挤出滚圆法制备法莫替丁微丸,通过多功能颗粒包衣机将含药丸芯包上三层功能各异的包衣层,并考察各层包衣液的处方组成和用量对微丸漂浮性能和缓释性能的影响。结果所得微丸大小均匀,圆整度良好,平均粒径为1.92mm,长短径比值为1.15。采用聚丙烯酸树脂Eudragit RL/RS(1∶3)混合物为内层包衣材料,碳酸氢钠为中间层,Eudragit RL为外层,制得的包衣微丸在0.1mol.L-1盐酸中2min内的漂浮率超过90%,且能维持漂浮24h以上。结论该微丸具有良好的缓释性能,释药行为符合一级动力学方程。     

厄贝沙坦缓释微丸的制备及体外释药特性的考察

目的制备厄贝沙坦缓释微丸,并对其体外释放度进行考察。方法采用流化床包衣技术,以丙烯酸树脂类Eudragit NE30D和Eudragit L30D-55混合水分散体为包衣材料,制备缓释微丸。考察不同释放介质、转速对其体外释药行为的影响。结果优化后的包衣处方为Eudragit NE30D/Eudragit L30D-55的比例为4︰1,抗粘剂和致孔剂的用量分别为聚合物干重的75%及20%,增重10%,熟化24h,释放介质的p H值对微丸释药的影响最明显,其体外释药过程符合一级释药模型。结论成功制备了厄贝沙坦缓释微丸,经考察其释放度符合要求。     

氟比洛芬聚丙烯酸树脂RL/RS固体分散体的制备

目的制备氟比洛芬固体分散体并考察其体外释药特性。方法以氟比洛芬为主药,分别以聚丙烯酸树脂Eudragit RL、RS及RL/RS混合物为载体,卵磷脂为乳化剂,以溶剂法制备固体分散体。以体外溶出半衰期t1/2为指标,优选固体分散体的最佳制备方法。结果氟比洛芬固体分散体的最佳处方比例为:药物∶载体=1∶9,RL∶RS=2∶1,卵磷脂浓度为0.2%。固体分散体体外溶出测定采用小杯法,测定波长为247 nm,分别采用紫外分光光度法和差示扫描热量法进行定量、定性分析。结论制备所得氟比洛芬固体分散体体外溶出缓慢、平稳、完全,达到提高生物利用度、12 h给药1次的缓释设计目的,可进一步制成其他剂型。     

A floating multiparticulate system for ofloxacin based on a multilayer structure: In vitro and in vivo evaluation

The purpose of this research was to develop a novel gastroretentive multiparticulate system with floating ability. This system was designed to provide drug-loaded pellets coated with three successive coatings-the retarding film (ethyl cellulose), the effervescent layer (sodium bicarbonate) and the gas-entrapped polymeric membrane (Eudragit RL 30D). The floating pellets were evaluated for SEM, floating characteristic parameters, in vitro release and bioavailability in New Zealand rabbits. The zero-order release theory model is designed to interpret the release processes. Due to the swelling property, high flexibility and high water permeability, Eudragit RL 30D was used as a gas-entrapped polymeric membrane. The obtained pellets exhibit excellent floating ability and release characteristics. Analysis of the release mechanism showed a zero-order release for the first 8h because of the osmotic pressure of the saturated solution inside of the membrane, which was in accordance with that predicted. Abdominal X-ray images showed that the gastroretention period of the floating barium sulfate-labeled pellets was no less than 6h. The relative bioavailability of the floating pellets compared with reference tablets was 113.06 ± 23.83%. All these results showed that the floating pellets are a feasible approach for the gastroretentive drug delivery system.     

Dual cross-linked pulsatile beads for chronotherapy of asthma: Development and evaluation

In the present investigation, pulsatile release beads were prepared by ionic gelation technique. Theophylline dual-cross-linked beads were prepared by dropping dispersed phase of theophylline, Delonix regia gum (DRG), and sodium alginate into the dispersion phase of different concentration of calcium chloride solution followed by aluminium chloride solution. The formulated beads were further coated by Eudragit L & S 100 in the ratio 1:2 w/w in order to achieve desired lag time. In vitro release study showed lag time of 5–7?h before release of theophylline from the formulated beads, which were found to be intact for 6?h. Thus, formulated dual cross-linked beads when administered at bed time may release theophylline when needed most for chronotherapeutics of early morning asthmatic attacks in chronic patients. In vivo radio imaging study carried out in New Zealand white strain rabbit confirms the findings of in vitro results.     

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.     

Formulation and evaluation of floating drug delivery system of famotidine

A multiple unit oral floating drug delivery system of famotidine was developed to prolong gastric residence time, target stomach mucosa and increase drug bioavailability. Drug and polymer compatibility was studied by subjecting physical mixtures of drug and polymers to differential scanning calorimetry. Cod liver oil entrapped calcium alginate beads containing famotidine, capable of floating in the gastric condition were formulated and evaluated. The gel beads were prepared by emulsion gelation method by employing sodium alginate alone and mixture of sodium alginate and hydrophilic copolymers such as carbopol 934P and hydroxypropylmethylcellulose K15M grade in three different ratios. The effect of selected factors, such as percentage of oil and amount of copolymers on floating properties was investigated. The beads were evaluated for percent drug loading, drug entrapment efficiency, buoyancy and in vitro drug release. The in vitro drug release study of the beads was carried out in simulated gastric media employing a modified Rosette-Rice test apparatus. Wherein, the apparatus was further modified by incorporating a water jacket to the apparatus to circulate hot water to maintain 37±2° for throughout the release study. All the oil entrapped calcium alginate beads floated if a sufficient amount of oil was used. Beads formulated employing sodium alginate alone could not sustain the drug release up to 8 h, whereas beads formulated with mixture of sodium alginate and copolymers demonstrated sustained release of famotidine up to 8 h. The results suggested that cod liver oil entrapped calcium alginate beads were promising as a carrier for intragastric floating drug delivery of famotidine.     

Preparation of Eudragit E100 microspheres by modified solvent evaporation method

The objective of this investigation was to develop the hollow microspheres as a new dosage form of floating drug delivery system with prolonged stomach retention time. Hollow microspheres containing ranitidine hydrochloride were prepared by solvent evaporation method using Eudragit RLPO dissolved in a mixture of dichloromethane and ethanol. The maximum yield and drug loading amount of hollow microspheres were 88.45% and 80 +/- 4.0%, respectively. The in vitro release profiles showed that the drug release rate decreased with increasing viscosity of Eudragit RLPO, while diameter of hollow microspheres increased with the increase of drug polymer weight ratio. Hollow microspheres could prolong drug release time (approximately 24 h) and float over stimulate gastric fluid for more than 12 h. These results demonstrated that ranitidine HCl hollow microspheres were capable of sustained delivery of the drug for longer period with increased bioavailability.     

Preparation and evaluation of a novel gastric floating alginate/poloxamer inner-porous beads using foam solution

In the present study, a simple and rapid method was developed to prepare a novel kind of inner-porous floating beads. The beads were prepared by dripping the foam solution into CaCl(2) solution using disposable syringe needle, where the foam solution consisting numerous of microbubbles with poloxamer 188 as foaming agents, alginate as foaming stablizer. Foamability and foam stability of different polymer ratios were evaluated. The SEM cross-section pictures of the beads showed that the beads were inner-porous and composed of bubbles with very thin wall bubbles stacked together. The visual observation result and the resultant-weight method confirmed that the floating beads showed good buoyancy, most beads could float in the stomach for more than 6 h. The floating beads release behavior in vitro showed that drug release from the beads in a sustained-release fashion for 10 h. Gamma scintigraphic images and pharmacokinetic studies in vivo showed that the beads can retained in the stomach for over 6 h and can improve the bioavailability of drug with narrow absorption window.     

Dissolution properties of control released solid dispersion of carvedilol with HPMC and Eudragit RS

In this study, solid dispersion for carvedilol was prepared by using spray-drying method. Solid dispersions were formulated with carvedilol and Eudragit RS and hydroxypropyl methylcellulose to control the dissolution rates of carvedilol. Scanning electron microscope was used to analyze surface of solid dispersion samples. Differential scanning calorimetry and powder X-ray diffraction were used to analyze the crystallinity of solid dispersions. Fourier transform infrared spectroscopy was used to analyze the change in chemical structure of solid dispersions. The release behavior of solid dispersion analyzed at simulated gastric fluid (pH 1.2) in in vitro study. The dissolution rate of carvedilol was higher than active pharmaceutical ingredient. In conclusion, we can control the dissolution rate by solid dispersion using biomedical polymers.