制备含抛射剂四氟乙烷的丙酸倍氯米松吸入气雾剂

Preparation of Beclometasone Dipropionate Inhalation Aerosol Containing Tetrafluoroethane as the Propellant

目的制备以四氟乙烷作为抛射剂的丙酸倍氯米松吸入气雾剂。方法采用析因设计,以微细粒子剂量作为主要评价指标进行处方筛选,以微细粒子剂量、每揿主药含量及递送剂量均一性作为关键质量指标进行最优处方验证,并在此基础上筛选出合适的驱动器。结果所选处方工艺制得的3批样品搭配Becotide?驱动器测得的微细粒子剂量均值为33. 1%,每揿主药含量在98. 3%～100. 7%,递送剂量均一性在87%～118%,与Becotide?相当,微细粒子剂量测定结果与预测值32. 9%接近,表明采用析因设计筛选处方及通过模型预测最优值是可靠的。自制样品搭配驱动器B测得的微细粒子剂量、质量中值空气动力学直径、几何标准差与Becotide?最接近,同时,每揿主药含量及递送剂量均一性结果均符合规定,因此选择驱动器B作为本品配套的驱动器。结论所选处方工艺稳定可靠,适合生产,成品宜配置驱动器B。

OBJECTIVE To prepare the beclometasone dipropionate inhalation aerosol using tetrafluoroethane as the propellant.METHODS Using the factorial design,the fine particle fraction was used as the main evaluation index to screen prescriptions;the fine particle fraction,delivered dose and uniformity of delivered dose were used as the critical quality indexes to verify the optimal prescription,and on this basis,the appropriate actuator was screened out.RESULTS The average value of fine particle fraction,the range of delivered dose and uniformity of delivered dose resulted from three batches of aerosol produced by the preferable prescription and process with the actuator of Becotide?were 33.1%,98.3%-100.7%,and 87%-118%,which was comparable to Becotide?,and the measured result of fine particle fraction was close to the predicted value of 32.9%by Design-Expert 8.0,indicating that to screen prescriptions by using factorial design and predict the optimal value through the model were reliable.The results of fine particle fraction,mass median aerodynamic diameter and geometric standard deviation measured by the self-made products with actuator B were the closest to Becotide?.Meanwhile,the results of delivered dose and uniformity of delivered dose were all in compliance with the requirement.Therefore,actuator B was selected as the matched actuator of this product.CONCLUSION The selected prescription and process are stable,reliable,and suitable for production,the final product should be configured with the actuator B.