流化床对过氧化氢包合物的防潮包衣研究

目的对过氧化氢的尿素包合物进行防潮包衣,并考察其防潮效果。方法利用共沉淀法制备过氧化氢尿素包合物,并用流化床顶喷对其颗粒进行防潮包衣,用正交设计考察包衣过程中各因素对包衣效果的影响。结果确定最佳条件为包衣液固含量10%,流速1.2 mL·min-1,雾化压力0.40bar,进风温度40℃,在此条件下所得产品包衣效率约为84%。结论流化床顶喷防潮包衣效率高,包衣后过氧化氢包合物稳定性提高。     

复方非伪调释胶囊的制备及流化床中试放大研究

目的采用流化床包敷/包衣法制备复方盐酸非索非那定/盐酸伪麻黄碱调释胶囊并进行流化床中试放大研究,为建立复方药物异步释放的24 h调释小丸研发和中试技术平台奠定基础。方法采用流化床批量递增设计以含量、收率、效率为主要考察因素,以溶出度和释放曲线作为评价指标,考察中试放大工艺。结果在包衣区温度和风速、雾化液滴大小相近的前提下,调整其他参数,可以将小试工艺顺利放大到中试。结论流化床包敷/包衣法制备复方非索伪麻调释胶囊的小试工艺可顺利放大到中试,为进一步扩大生产奠定了基础。     

氟比洛芬乙基纤维素水分散体包衣小丸的制备及体外释药特性

目的：制备氟比洛芬包衣小丸，评价其体外释药特性。方法：离心造粒法制备空白丸芯及载药小丸；以乙基纤维素水分散体为包衣材料，羟阿基甲基纤维素为致孔剂，流化床制备氟比洛芬包衣小丸；释放度实验考察小丸的体外释药特性。结果：包衣小丸缓释胶囊的释放曲线与进口缓释胶囊ForbensR相似，羟丙基甲基纤维素的用量和介质pH值对释药影响显著，而热处理时间和胶囊壳对释药无显著性影响。结论：氟比洛芬包衣小丸具有较理想的体外缓释效果。     

国产乙基纤维素水分散体用于吲哚美辛缓释小丸的包衣工艺研究

目的：研究国产乙基纤维素水分散体包衣吲哚美辛缓释小丸的包衣工艺.方法：以国产乙基纤维素水分散体为包衣材料,添加癸二酸二丁酯为增塑剂,设计正交试验,在流化床中以不同操作条件制备吲哚美辛缓释小丸,考察小丸的药物释放度,并用电镜观察了小丸表面特征.结果：采用合适的流化床包衣工艺,采用国产乙基纤维素水分散体包衣能够制得和市售品（有机溶剂包衣）释放性能相似的吲哚美辛缓释小丸.结论：包衣工艺参数能够明显影响缓释小丸的药物释放度和表面特征.     

颗粒包衣工艺提高鱼腥草素钠的稳定性

目的:对鱼腥草素钠(SH)进行颗粒包衣,提高其稳定性。方法:采用羟丙甲基纤维素(HPMC)为包衣材料,用流化床项喷技术对SH颗粒进行包衣,以收率为指标,考察了包衣增重、增塑剂用量、包衣温度、黏合剂等因素对包衣收率的影响,筛选包衣处方及优化制备工艺参数,并通过稳定性考察包衣后鱼腥草素钠的稳定性。结果:优化后的包衣处方是包衣增重为15%,增塑剂用量为5%,包衣温度为60℃。包衣颗粒中SH含量是(86.6±0.4)%(g/g,n=9)。SH包衣颗粒在高温、高湿条件下放置10 d,稳定性很好。结论:SH原料颗粒经过HPMC包衣后能有效提高其稳定性。     

自相似流量关键参数分析

大量的研究结果表明,网络流量过程普遍存在着自相似和长相关特性,自相似和长相关特性对网络性能具有重要的影响.目前绝大部分研究都集中在Hurst系数的估计及其性能影响上,这是不全面的.本文深入研究影响网络性能的自相似流量关键参数,通过仿真分析Hurst系数和方差系数对网络性能的影响,表明Hurst系数和方差系数对网络性能均有重要的影响.分析了方差对网络性能影响的原因,研究了G与方差之间的关系及其计算方法,给出了基于IDC的复合分形更新过程参数的估计算法,分析了分形开始时间对网络性能的影响.     

流化床制粒法制备中药纯浸膏包衣微丸的工艺研究

目的:制备半夏泻心汤中药纯浸膏包衣微丸.方法:采用流化床制粒法,考察纯浸膏粉的起母模丸条件、母模丸增大及包衣处理中的处方因素对微丸的形成和收率的影响.结果:在微丸起母模丸阶段,以纯浸膏粉及含醇量30%以上的中药浸膏起模,在母模丸增大阶段采用中药浸膏作为微丸增大剂是可行的,微丸增大后用德固萨作包衣剂,其防潮性能良好.结论:按所选的处方及工艺条件,用流化床制粒法可制得表面光滑、圆整度较高且防潮性能好的半夏泻心汤中药纯浸膏包衣微丸.     

蜂蜡和热处理掩蔽药物苦味的研究

掩盖药物不良味道，可提高病人的顺应性和产品价值。但既不降低生物利用度又可掩盖药物不良味道的方法尚无报道。作者采用由氢化油和表面活性剂组成的混合包衣液，在流化床中对盐酸前氯滚（大脑兴奋剂，有苦涩味）微粒进行侧面喷雾法包衣。制备无苦味又不降低生物利用度的粉剂。观察了温度和热处理过程对溶出作用和包衣颗粒表面状态的影响，通过对包衣材料进行差示扫描量热测定（DSC）和包衣层表面状态的观察，阐明了热处理影响的机理。1方法（l）2％粉剂的制备：盐酸荷氯咬过100目筛除去大微粒。用流化床制粒包衣机制粒，并采用不同包衣…     

薄膜包衣放大生产过程中关键因素的考量

［摘要］目的：介绍薄膜包衣放大生产过程中一些关键因素与包衣产品质量的关系。方法：分述了包衣过程中片剂混合均匀度的影响因素、设备干燥能力的构成及喷液速度的影响因素。结果：在薄膜包衣放大生产过程中,载药量、片芯的质量与设计、挡板的类型、锅体转速、设备的干燥能力及喷液速度等是影响包衣产品质量的关键因素。结论：通过对上述关键因素的调节,可以实现产品质量的稳定性与重现性。     

具有杰出水汽阻隔性能的新型速释薄膜包衣系统——欧巴代(R)200新一代优化型薄膜包衣系统

上世纪90年代,卡乐康公司(www.colorcon.com.cn)在全球推出了以聚乙烯醇(PVA)为成膜材料的包衣系统.因具有黏度低、成膜性好、防潮性能强等优点,PVA被广泛用于各种片剂的薄膜包衣.从2007～2009年美国FDA批准的新药审批(NDA)数据来看,PVA已取代羟丙甲纤维素(HPMC),成为全配方包衣预混系统首选的成膜材料. 理想的速释薄膜包衣系统应具有包衣效率高、防潮性能好、对片芯的释放没有影响等特征.欧巴代(R)200 (Opadry(R) 200)是卡乐康最新优化的速释包衣系统,通过配方优化,保留了各种高分子材料用于速释薄膜包衣的优点.欧巴代(R) 200是适用于挑战性片芯的薄膜包衣系统,具有卓越的防潮性能和杰出的颜色稳定性,能够在更高的固含量条件下实现稳定的包衣.本文报道了欧巴代(R) 200的各种基础性能及在模型药物上的应用.     

Suppression of agglomeration in fluidized bed coating. II. Measurement of mist size in a fluidized bed chamber and effect of sodium chloride addition on mist size

It has been reported that the degree of particle agglomeration in fluidized bed coating is greatly affected by the spray mist size of coating solution. However, the mist size has generally been measured in open air, and few reports have described the measurement of the mist size in a chamber of the fluidized bed, in which actual coating is carried out. Therefore, using hydroxypropylmethyl cellulose (HPMC) aqueous solution as a coating solution, the spray mist size of the coating solution in a chamber of the fluidized bed was measured under various coating conditions, such as the distance from the spray nozzle, fluidization air volume, inlet air temperature and addition of sodium chloride (NaCl) into the coating solution. The mist size in the fluidized bed was compared with that in open air at various distances from the spray nozzle. Further, the relationship between the spray mist size and the degree of suppression of agglomeration at various NaCl concentrations during fluidized bed coating was studied. The mist size distribution showed a logarithmic normal distribution in both cases of the fluidized bed and open air. The number-basis median diameter of spray mist (D50) in the fluidized bed was smaller compared with that in open air. D50 increased with the increasing distance from the spray nozzle in both cases. In the fluidized bed, D50 decreased with the increasing fluidization air volume and inlet air temperature. The effect of NaCl concentration on the mist size was hardly observed, but the degree of suppression of agglomeration during coating increased with the increasing NaCl concentration in the coating solution.     

顶喷式流化床包衣效果的影响因素研究

选择平均粒径为250μm的石英砂作为模型,分别用Eudragit NE30D水分散体与Eudragit RL乙醇溶液包衣,用正交设计考察流化床顶喷过程中各因素对包农效果的影响.结果表明,用Eudragit NE30D水分散体包衣时,包衣液流速和雾化压力对包衣效果影响较大,用Eudragit RL乙醇溶液包衣时则是增塑剂浓度的影响较大.     

Fluidization technologies: Aerodynamic principles and process engineering

The concept of fluidization has been adapted to different unit processes of pharmaceutical product development. Till date a lot of improvements have been made in the engineering design to achieve superior process performance. This review is focused on the fundamental principles of aerodynamics and hydrodynamics associated with the fluidization technologies. Fluid-bed coating, fluidized bed granulation, rotor processing, hot melt granulation, electrostatic coating, supercritical fluid based fluidized bed technology are highlighted. Developments in the design of processing equipments have been explicitly elucidated. This article also discusses processing problems from the operator's perspective along with latest developments in the application of these principles. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3933–3960, 2009     

Bead layering as a process to stabilize nanosuspensions: influence of drug hydrophobicity on nanocrystal reagglomeration following in-vitro release from sugar beads

Objectives In this article the feasibility of fluidized bed bead coating of nanosuspensions of drugs with significantly different physicochemical properties was investigated as a process to transform nanosuspensions into a solid dosage form. The second aim was to see how those physicochemical properties affect the coating process and the subsequent in‐vitro dissolution process. Methods Naproxen and cinnarizine were used as model drugs. A fluidized bed pellet coater with Würster insert was used to coat the nanosuspensions prepared by media milling on sugar beads. Key findings Bead layering of cinnarizine nanosuspensions resulted in a complete dissolution in 15 min, compared to only 11% in 1 h for the unmilled powder. Naproxen also dissolved three times faster when formulated on a bead. A difference could be observed between naproxen and cinnarizine. Cinnarizine nanocrystals reagglomerate when released from the coating, resulting in a slower release when compared to the original nanosuspension. No agglomeration and no delay could be observed for naproxen. These differences are most likely caused by the difference of surface hydrophobicity between naproxen and cinnarizine. Conclusion This study confirms that bead layering is a valuable drying technique that could complement spray drying and freeze drying, but more important is that we prove that drug physicochemical properties have a significant influence on in‐vitro dissolution performance after bead layering and this is not readily predictable from the information obtained from the original nanosuspension itself.     

Quantification of microparticle coating quality by confocal laser scanning microscopy (CLSM)

In this work, a novel protocol was developed for determining film coating thickness and coating quality of microparticles, based on the use of confocal laser scanning microscopy (CLSM). CLSM was found to be an adequate non-destructive technique for the quantification of the coating thickness and coating quality of individual thin-coated small particles. Combined with image analysis, it was possible to derive with high accuracy the coating thickness distribution of a representative number of microparticles. The performance of the novel methodology was assessed by the quantification of the coating thickness and coating quality of protein-coated microparticles produced by fluidized bed coating. It was found that the CLSM data on coating layer thickness were generally in good agreement with the results from chemical analysis, down to a thickness of 1–1.5 μm. Using CLSM the importance of setting up the appropriate distance between the coating nozzle and the powder bed with respect to microparticle coating quality in fluidized bed processing was illustrated. Coating quality was found to decrease with increasing distance the coating droplets have to travel before impinging onto the core particles as a result of spray-drying of the coating droplets. Also, coating quality decreased with increasing viscosity of the coating droplets, resulting in reduced spreading on the cores.     

硫酸沙丁胺醇缓释微丸的制备及其释放度研究

目的制备硫酸沙丁胺醇缓释微丸并考察其体外释放度。方法采用流化床底喷包衣技术,在已有处方工艺研究的基础上,进一步考察致孔剂用量及缓释层增重对其释放度影响。用高效液相色谱法测定其释放度。结果致孔剂在缓释层中的用量占该固体总量的0.22%,缓释层增重为8.55%时,所制备微丸的释放度最优,该微丸释药行为符合一级方程。结论方法简单,工艺可行,质量稳定,释放度符合药典规定要求。     

流化床颗粒包衣法制备替米沙坦氢氯噻嗪片

目的 采用流化床颗粒包衣法制备替米沙坦氢氯噻嗪片,并对其稳定性进行考察。方法 采用流化床一步造粒工艺制备替米沙坦颗粒,然后将替米沙坦颗粒进行不同包衣增重后与氢氯噻嗪以及合适的辅料混合,用普通旋转压片机进行压片制备替米沙坦氢氯噻片,并利用正交试验设计,优化替米沙坦氢氯噻嗪片处方;用HPLC进行含量和杂质检测,通过加速试验和长期试验考察片剂稳定性和溶出度。结果 该方法制备的替米沙坦氢氯噻嗪片质量稳定。羧甲基淀粉钠外加用量20.4 mg、氢氧化钠用量8.5 mg溶出指标最为理想,最终优化的处方与原研制剂溶出特征一致。结论 以流化床颗粒包衣法制备的替米沙坦氢氯噻嗪片质量稳定,工艺较双层片简单,具有可行性。     

流化床制粒制备甘芝口含片

目的：制备甘芝口含片。方法：采用流化床制粒,以颗粒流动性、含片崩解时限及外观性状为考察指标,通过正交试验优选最佳制粒工艺参数。结果：最佳工艺参数为A1B2C3D3,即进风温度为45～50℃、物料温度40～45℃,雾化压力0.8～1.0bar,料液流速5～7ml/min。结论：该制备工艺简单,方法可行,可应用于大生产。     

A burst drug release caused by imperfection of polymeric film-coated microparticles prepared by a fluidized bed coater

The aim of this study was to investigate the drug release from microparticles coated with various polymeric films. Ibuprofen-loaded microparticles with diameter of 250 and 300 microm were prepared by a fluidized bed granulator. Five polymers were used as coating materials, i.e., ethylene vinyl acetate, ethyl cellulose, ethyl cellulose aqueous dispersion, polyethacrylate or Eudragit NE 30D, and carnauba wax. The coating was performed with a fluidized bed coater. Afterwards the coated microparticles were characterized in terms of particle size, morphology, and drug content. The drug dissolution was also investigated in pH 7.4 phosphate buffer. In our attempts for production of extended release ibuprofen microparticles coated with polymeric films, it was shown that the coating process had a significant effect on drug release. The undesired burst release of ibuprofen was observed in all film-coated microparticulate formulations, resulting from the imperfection of coating films.