不同药用辅料流化床制粒的物性质量分析研究

目的研究5种药用辅料制粒后颗粒的物性指标,分析探讨颗粒物性指标的相关性及颗粒物性质量。方法采用Pearson相关性分析法分析颗粒的7项评价指标相关性,采用主成分分析法对颗粒物性指标进行主成分分析和综合评价。结果粒径分布宽度与松密度及振实密度呈极显著正相关,松密度与振实密度呈极显著正相关,振实密度与压缩度呈显著正相关。对第一主成分产生正向影响较大的物性指标是粒径分布宽度和振实密度。乳糖+水制成的颗粒及甘露醇+水制成的颗粒综合评价得分较高,可溶性淀粉+HPMC制成的颗粒综合评价得分最低。结论不同药用辅料制成的颗粒物性质量存在差异,乳糖和甘露醇分别以水为粘合剂制成的颗粒物性质量较好,可溶性淀粉以HPMC为粘合剂制成的颗粒物性质量较差。     

流化床包衣法制备银耳多糖肠溶微粒

目的 考察并优化流化床包衣法制备银耳多糖肠溶微粒(ETPP)工艺条件.方法 以Eudragit L30-D55水分散体为包衣材料,柠檬酸三乙酯为增塑剂,滑石粉为抗黏剂,同时考察包衣后微粒的累计释放度,制备直径小于190 μm肠溶微粒.结果 载药量为40.62％,包封率为79.29％,酸中累计释放度小于10％,碱液中累计释放度大于75％,制备的微粒其平均粒径在115～190um之间,圆整度、堆密度、总收率均较理想.结论 应用流化床包衣法制备ETPP,其工艺简便,稳定可行,适合小鼠药物药理学和毒理学研究的需要和大工业生产.     

Taste masking of naproxen sodium granules by fluid-bed coating

Abstract

The taste of oral dosage forms is an important argument regarding patient’s compliance and acceptability. For this reason, it is often necessary to mask an undesirable and unpleasant taste of an active pharmaceutical ingredient. The purpose of this study was to mask the taste of naproxen sodium by a new fluid-bed coating approach. Different compositions of coating suspensions were used to coat naproxen sodium granules. It was found that products with the addition of a plasticizer were not stable at 40?°C and tended to agglomerate. Subsequently, formulations without plasticizer were used and the ratio between water and Eudragit® E was varied. Increasing the fraction of water in the suspension from 3% to 14% reduced the effective release of naproxen sodium. An optimum ratio between naproxen sodium granules and Eudragit® E was found to be 1:1.576, where less naproxen sodium was released than the threshold bitter value and an appropriate taste masking for more than 5?min was guaranteed. Investigation of the particle size distribution revealed a d¹⁰ of 138.35?±?21.52?µm, a d^50?=?256.40?±?11.27?µm and a d^90?=?500.85?±?69.08?µm, which guarantees an acceptable mouthfeel for patients.     

The Development of a Microwave Fluid-Bed Processor. II. Drying Performance and Physical Characteristics of Typical Pharmaceutical Granulations

Four typical pharmaceutical granulations were used to measure the enhanced drying performance of a laboratory-sized microwave fluid-bed processor, the design and construction of which were presented in Part I of this work (preceding paper). Results demonstrate improvements in observed drying rates by as much as sixfold depending upon the granulation type and drying conditions. At a low inlet temperature (30°C), drying was achieved with microwave power inputs of 100–125 W/liter of working capacity, whereas similar targeted moisture levels were unattainable using conventional fluid-bed drying. Microwave energy available for heating and drying was 68 to 86% of the total microwave energy inputted.     

Preparation and in vitro/in vivo evaluation of esomeprazole magnesium-modified release pellets

To reduce the drug plasma concentration fluctuation without being destroyed by gastric fluid, novel Esomeprazole magnesium modified-release pellets (EMZ-MRPs) with suitable in vitro release profiles and good in vitro and in vivo correlation (IVIVC) were developed. Fluid-bed was used to obtain EMZ-loaded pellets by spraying drug suspension onto blank sugar pellets. The drug-loaded pellets were subsequently coated with Eudragit® RS30D/RL30D (ERS/ERL) aqueous dispersion to achieve sustained-release (SR) characteristics. Furthermore, the SR pellets were coated with Eudragit® L30D-55 (EL-55) aqueous dispersion to achieve enteric properties. Besides, isolated coating film was necessary between drug layer and SR layer, as well as SR and enteric-coated layer to protect from their possible reaction. The resulting pellets were filled into the hard gelatin capsules for in vitro release processing and single-dose pharmacokinetic study in rats. The optimal formulation achieved good SR feature both in vitro and in vivo with a relative bioavailability of 103.50%. A good IVIVC was characterized by a high coefficient of determination (r?=?0.9945) by deconvolution method. Compared to those of EMZ enteric-coated pellets (EMZ-ECPs, trade name NEXIUM), the in vivo study make known that the EMZ-MRPs with decreased maximum plasma concentration (C_max), prolonged peak concentration time (T_max) and mean residence time (MRT), and similar values both area under concentration–time curve from 0 to t (AUC_0–t) and 0 to infinity (AUC_0–∞). Collectively, these results manifested EMZ-MRPs had a satisfactory sustained-release behavior, a desired pharmacokinetic property, improved in vivo retention and decreased plasma drug concentration fluctuation.     

黄芩苷纳米晶体微丸的制备及其药代动力学初步研究

目的:该研究制备了黄芩苷纳米晶体(baicalin nanocrystal,BC-NC),并进行了大鼠体内药物动力学研究.方法:采用探头超声结合高压均质法制备黄芩苷纳米混悬剂,然后通过流化干燥工艺将其脱水干燥成固体微丸,考察纳米晶体的形态、粒径分布、Zeta电位.以黄芩苷为指标成分,采用HPLC测定大鼠灌胃给药后的血药浓度,用DAS 2.0药动学软件计算药代动力学参数.结果:黄芩苷纳米晶体在扫描电镜下呈不规则颗粒状,平均粒径(248±6) nm,多分散指数(PI)为(0.181±0.065),Zeta电位为(-32.3±1.8)mV.BC-NC达峰浓度(Cmax)为(16.51±1.73) mg·L-1,0～24h的药时曲线下面积(AUC)增加为(206.96±21.23) mg·L-1·h,与黄芩苷原料药及物理混合物相比均有显湿著性提高(P＜0.0l).结论:通过高压均质及流化干燥工艺制得的黄芩苷纳米晶体能显著提高药物体内生物利用度,有望进一步制成口服固体制剂.     

Aqueous Ethylcellulose Dispersion of Ethylcellulose. I. Evaluation of Coating Process Variables

Formulation and process variables play an important role in the film-forming properties of coating polymers. Three selected independent coating process variables, namely, percent solids content in the coating polymeric dispersion, inlet-air temperature, and spray rate of the polymeric dispersion, were investigated in this study to determine their effect on the performance characteristics of tablets coated with a plasticized aqueous ethylcellulose dispersion (Surelease) in a fluid-bed equipment. Response surface methodology (RSM) was utilized to study the complex relationship between these process variables and selected response variables. Three response variables were considered, namely, rate of drug release from the untreated coated tablets and the thermal-treated coated tablets and microindentation hardness of the untreated coated tablets. A 12-point factorial experimental design was utilized, and three-dimensional (3-D) response surface plots were generated using a second-order polynomial model. The model provided information needed to predict optimal process conditions. Drug release from the coated tablets followed zero-order kinetics. Inlet-air temperature was found to be the most critical process variable for all the three response variables studied. A correlation was observed between the drug release rate and the microindentation hardness of the applied polymeric coat in the case of untreated coated tablets. The 3-D response surface plots indicated that lower rates of drug release from the coated tablets may be obtained by using high inlet-air temperature and low spray rate of the polymeric dispersion during coating.     

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。     

Modeling and Monitoring of Polymorphic Transformations During the Drying Phase of Wet Granulation

PURPOSE: The purpose of this work was to monitor polymorphic transformations of glycine during the drying phase of a wet granulation and model the polymorphic conversions using a time-based reconciliation model. METHODS: Near-infrared spectroscopy (NIR) was used for quantitation of polymorphs, and X-ray powder diffraction (XRPD) was used for qualitative analysis of polymorphs. RESULTS: The data show that the faster the granulation was dried, the more kinetic trapping of the metastable alpha-glycine polymorph, as predicted by reconciliation of the time scales of both the drying rate and the rate of the solution-mediated conversion. CONCLUSIONS: By knowing basic properties of the drug substance (solubility of the polymorphic forms and the rate of the solution-mediated conversion), processing conditions, such as the drying rate, can be adjusted to anticipate and prevent potential polymorphic transformations.     

不同淀粉在流化床制粒中的应用

流化床制备咖啡因颗粒，测试颗粒的流动性和可压性，比较粘合剂Starch1500与普通淀粉的不同。