硫酸沙丁胺醇口腔崩解片的制备及质量评价

目的：优选硫酸沙丁胺醇口崩片直压工艺，并测定其含量。方法：采用因子设计优选口崩片直压工艺，以直压甘露醇（pearlitol 200 DC）（X1）、交联聚维酮（PVPP）（X2）、微粉硅胶（silicon dioxide）（X3）、硬脂酸镁（MS）（X4）为自变量，以直压粉末的休止角（angle of repose）（Y1）、片子硬度（Hardness）（Y2）以及崩解时限（Disintegration）（Y3）为变量建立方程，最终确定直压工艺；采用反相高效液相色谱法测定样品含量。结果：X1、X3显著影响Y1，方程为Y1=35．8375—0．03125X1＋0．4X3-0．0425X1X3；X4显著影响Y2，方程为Y2=5．73875—0．54125X4；X2、X4显著影响Y3，方程为Y3=75—1．975X2＋20．375X4，通过等值线确定最佳处方，并且最佳处方的理论预测值在真实值波动范围内；硫酸沙丁胺醇在4～200ug／ml范围内线性良好，回收率为99．6％，RSD值为0．62％（n=9）。结论：硫酸沙丁胺醇直压工艺简便可行，建立的反相高效液相色谱法可用于硫酸沙丁胺醇口崩片的含量测定。

Preparation and evaluation of salbutamol sulfate oral melt tablets

Objective ：The purpose of the present study was to develop an optimized direct compression technique of salbutamol sulfate oral melt tablets and to establish an RP-HPLC method of determination for salbutamol sulfate. Methods：A 24 factorial design was employed in formulation with quantity of direct compression mannitol （pearlitol 200 DC）（X1）, crospovidone（PVPP） （X2）, colloidal silicon dioxide （X3） and content of magnesium stearate （X4） as independent variables. Three dependent variables were considered： angle of repose（Y1）, tablet hardness（Y2）, tablet disintegration（Y3）. The main effect and interaction terms were quantitatively evaluated using a mathematical model; Active pharmaceutical ingredient（API） of salbutamol sulfate oral melt tablets was determinated by RP-HPLC. Results： The results indicate that X1 and X3 significantly affected Y： X4 significantly affected Y2; X2 and X4 significantly affected Y3, Regression analysis and numerical optimization were performed to identify the best formulation; The predicted values agreed well with the experimental values; the linearity was obtained over the range of 4-200 ug/ml, the average recovery was 99.6% ,RSD was 0.62% （n=9）.Conclusion：The results demonstrate the feasibility of the optimized direct compression technique taking salbutamol sulfate as a model drug and the method set up by RP-HPLC can determinate API of Salbutamol Sulfate oral melt tablets .