妥洛特罗透皮贴剂的释放度测定及不同测定方法结果比较

Determination of the Release Rate of Tulobuterol Transdermal Patch and Results Comparison of Different Methods

关键词:  妥洛特罗  透皮贴剂  桨碟法  转筒法  释放度  释放曲线

Key words:  tulobuterol  transdermal patch  paddle over disk  rotating cylinde  release rate  release curve

摘要:

目的 建立妥洛特罗透皮贴剂的释放度测定方法，并对不同装置测定的释放曲线进行比较。方法 采用中国药典2015年版收载的2种透皮贴剂释放度测定新方法，即桨碟法和转筒法，规定时间点取样后采用HPLC测定，色谱柱为Agilent C₁₈（250 mm×4.6 mm，5 μm），流动相为乙腈-0.02 mol·L^-1磷酸盐缓冲液（pH 3.0）（32：68），流速为1.0 mL·min^-1，柱温为35℃，检测波长为215 nm。分别考察妥洛特罗透皮贴剂在500 mL水中24 h的释放曲线，并对2种方法的释放曲线进行拟合，比较二者的相似性。结果 妥洛特罗在0.103~4.135 μg·mL^-1内线性关系良好（r=0.999 9），回收率为99.8%（n=9），样品溶液在24 h内稳定。将2种方法测定的释放度结果经Weibull方程拟合后得到的参数进行方差分析，2组数据间无显著性差异。结论 中国药典2015年版透皮贴剂释放度测定桨碟法（方法2）和转筒法均可用于妥洛特罗透皮贴剂的释放度测定，两者的测定结果不存在差异。

Abstract:

OBJECTIVE To establish a method for determining the release rate of tulobuterol patch, evaluate the consistence of the release curve between different test methods. METHODS Two kinds of new transdermal release test methods in China Pharmacopoeia 2015 Edition (paddle over disk method and rotating-cylinder method) were used, the concentration of each sampling point was determined by HPLC. Agilent C₁₈(250 mm×4.6 mm, 5 μm) column was used with the mobile phase of a mixture of acetonitrile and 0.02 mL·min^-1 phosphate buffer (pH3.0) (32:68), the flow rate was 1 mL·min^-1, the column temperature was 35℃, and the detection wavelength was 215 nm. Transdermal release behavior of tulobuterol patch in 500 mL water were investigated in 24 h, and similarity of the release curves was compared. RESULTS The linear correlation of tulobuterol was observed in the range of 0.103-4.135 μg·mL^-1(r=0.999 9), with a recovery rate of 99.8%(n=9), and the sample solution was stable in 24 h. The results of the two methods were analyzed by Weibull equation, and there was no significant difference between the two methods. CONCLUSION Paddle over disk method (method 2) and rotating-cylinder method in China Pharmacopoeia 2015 Edition can both be used to determine the release of tulobuterol transdermal patch, and the results of these two methods are identical.