Tamsulosin hydrochloride was used as the model drug to apply the quality by design theory in preparing sustained-release pellets. The drug-containing cores were prepared by extrusion-spheronization, and then the cores were coated with a fluidized bed to form the enteric-coated sustained-release pellets. After the reference was deeply analyzed, the critical quality attributes were determined as the drug release in pH 1.2 for 2 h and the accumulative release after the pallets were transferred to pH 7.2 buffer for 1 h and 3 h. According to the risk assessment, the most significant risk factors were determined as the percentage of Eurdragit?NE30D in the core (X1), the percentage of Eudragit?L30D-55 in the coating membranes (X2) and the coating weight gain (X3). The central composite design-response surface method was chosen to describe the relationship between the high risk factors and the critical quality attributes. From the response surface, the design space of the risk factors was confirmed as: X1at 18.8%-21.0%, X2 at 15.0%-20.2% and X3at 4.3%-6.1%. With the above space, the quality-controlled products that meet the expectation were got.

目的 制备盐酸美金刚缓释胶囊并对其含量进行测定.方法 采用流化床上药包衣的方法制备盐酸美金刚缓释微丸.含量测定采用气相色谱系统,HP-5(agilent,30m×0.32mm×0.25μm)毛细管色谱柱,氢火焰离子(FID)检测器,载气为氮气,柱温为程序升温,不分流直接进样;以盐酸金刚烷胺为内标物,测定盐酸美金刚缓释胶囊含量.结果 盐酸美金刚浓度在2.881~37.044μg·L-1范围内,与主成分和内标的峰面积比值呈良好的线性关系,r=0.9999;定量限为0.132ng;重复性试验RSD为1.35%(n=6);不同水平回收率的RSD为0.95%(n=9).自制的三批样品平均含量分别为(99.67±0.58)%、(99.80±1.09)%、(100.31±1.20)%.结论 盐酸美金刚缓释胶囊制备工艺稳定;气相色谱法准确、重复性好,可用于本品的含量测定.

Objective: The experiment aims is to optimize the coating formulation of memantine hy-drochloride sustained-release pellets by central composite design-response surface methodology (CCD-RSM). Methods: The ratio of pore former (A) and coating level (B) were selected as independent variables, and the in vitro accumulated releases from the pellets at 2, 4, 8 and 16 h were regarded as dependable vari-ables. Multilinear, two and three order quadratic models were applied to estimate the relationship between the independent and dependent variables and the two order quadratic model fitted best. The optimal formu-lations were selected from the overlaps of contour plots. Finally the optimal formulation was verified and f2 value was calculated to investigate the similarity of self-made product and Namenda XR ?. Results: Ac-cording to the CCD-RSM, the optimum values at the pore former level and coating level ranged from 14.0% to 18.0% and 4.5% to 7.7%, respectively. In pH 1.2 hydrochloric acid buffer, the f2 factor of self-made product and Namenda XR?was higher than 50 which showed the self-made product had similar dis-solution behavior as the brand-name drug. Conclusion: The model developed by CCD-RSM can be used for formulation optimization of memantine hydrochloride sustained-release pellets with good predictive accu-racy. According to the in vitro release behaviors, the self-made product is similar to the brand-name drug.

OBJECTIVE To develope a new method for the determination of pellets relative sphericity by using commercially available omeprazole enteric-coated pellets as model drug.METHODS The initial morphological analysis of the samples was carried out by image analysis method.Then the relative sphericity was quantitatively measured and analyzed by the circular surface rolling method combined with the characteristics of pellets.RESULTS The relative sphericity of multi-batch samples A was ＞80％,and there was no significant difference in the relative sphericity in batches.The pellet samples produced by each manufacturer had great differences in appearance morphology,the relative sphericity were (82.74±1.48)％,(88.03±3.40)％,(88.20±3.42)％ and (65.63±5.91)％ for sample A,B,C and D,indicating that the domestic manufacturers in the prescription composition,preparation process or key process parameters control conditions were likely to exist some differences.CONCLUSION The established method is simple,good for large samples and accurate.

采用磷脂/吐温80体系制备普通水飞蓟素纳米乳(SM-NE),通过静电作用在其表面吸附乳铁蛋白得到乳铁蛋白修饰的水飞蓟素纳米乳(LF-SM-NE),分别考察两者包封率、形态、粒径、Zeta电位,随后采用LC-MS/MS测定经口给药后大鼠体内的吸收情况.研究结果显示,当乳铁蛋白浓度为0.15 mg/mL,温孵时间为4h时,乳铁蛋白在SM-NE表面的吸附趋于饱和,所得LF-SM-NE外观圆整呈类球状,平均粒径(257±5.9)nm,Zera电位-(33.1±1.5)mV,包封率为(96.9±1.9)％,载药量为(3.90±0.12)％;与普通水飞蓟素纳米乳相比,经LF修饰后的SM-NE在大鼠体内的药物浓度显著增高,cmax和AUC均提高约2倍左右.因此,经LF修饰后的SM-NE可进一步提高药物的在体内吸收,是一种新型纳米粒口服吸收增强技术,具有良好的应用潜能.

目的 建立同时测定多西他赛注射用浓溶液中的溶血磷脂酰乙醇胺（LPE）、溶血磷脂酰胆碱（LPC）含量的HPLC-ELSD。方法 采用YMC Pack PVA-Sil（150mm×2mm,5μm）色谱柱,以三氯甲烷为流动相A、甲醇-水（93.5∶6.5）为流动相B,梯度洗脱,流速为0.4mL·min1,柱温为25℃,蒸发光散射检测器检测,检测器漂移管温度：100℃,雾化气：空气,气体流量为2.0L·min1。结果 LPE和LPC峰面积的对数与相应的浓度的对数呈良好的线性关系,线性范围分别为0.203~0.811μg（r=0.9990）和0.407~6.102μg（r=0.9996）,LPE3个浓度的平均加样回收率分别为104.1%,95.1%,101.6%,RSD分别为3.8%,0.3%,2.4%,LPC3个浓度的平均回收率分别为108.7%,104.5%,105.5%,RSD分别为1.0%,3.0%,2.6%。结论 该法简单、准确、重复性好,可用于多西他赛注射用浓溶液中大豆磷脂分解产物的质量控制。

Objective:To establish a HPLC method for the determination of icariine in Guchongzhixue Oral Liquid.Methods: The determination was carried out by RP-HPLC with octodelyl silicohydrides silanes bonded silica gel as a packing material,acetonitrile-Methanol-phosphoric(22∶9∶69) as a mobile phase,detection wavelength at 270 nm.Results: Icariine showed a good linear relationship at the range of 0.2～1.8 μg(r=0.999 9).The average recovery of icariine was 98.91%(RSD=2.06%,n=6).Conclusion: The method is sensitive,accurate,reproducible and specific,which can be used for quality control of Guchongzhixue Oral Liquid.

Objective:To optimize the macroreticular absorption resins for purifying the flavonoids of Lonicera japonica Thunb.and Chrysanthemum morifolium Tzvel.,so as to provide an experimental basis for extraction and purification of the flavonoids.Methods:Comparing the absorption,desorption and absorption kinetics among fourteen kinds of macroreticular absorption resins.Results: Macroreticular absorption resin HPD100 was suited for purification of two flowers' flavonoids.Through its absorption and elution,the absorption capacity was 69.30 mg/g and elution ratio could reach 87.1%.Conclusion:Macroreticular absorption resin HPD100 possessed high absorption capacity,and was apt to absorb and elute,so its capability was obviously higher than any other resins.

OBJECTIVE:To optimize the extraction and purification conditions for total flavonoids in Lonicera japonica Thunb. and Chrysanthemum morifolium Tzvel.METHODS:Comparision of several extraction processes, the L9 (3(4)) orthogonal design and macroreticular absorption resin D101 purification technique were performed.RESULTS:The optimum extraction conditions were 8 volume of 55% ethanol, 1 h refluence at 100 degrees C , water bath for 2 times. The extracted fluid was absorbed with the resin D101. The elutions were water, 30% enthanol, 70% enthanol. The obtained elution of 70% enthanol was evaporated and the content of total flavonoids was 62. 7%.CONCLUSION:The method is simple, approved and fit for industrial production.