处方设计及冻干工艺对注射用盐酸吡柔比星稳定性的影响

Effects of Formulation Design and Freeze-drying Process on Stability of Pirarubicin Hydrochloride for Injection

关键词:  盐酸吡柔比星  注射剂  冻干曲线  配液工艺  处方设计

Key words:  pirarubicin hydrochloride  injection  freeze-drying curve  preparation technology  formulation design

摘要:

目的 制备盐酸吡柔比星冻干制剂，考察处方设计及冻干工艺对产品质量的影响。方法 采用冻干工艺制备注射用吡柔比星，分别考察赋形剂种类和用量、中间体配液pH值控制及冻干曲线设计对吡柔比星稳定性的影响。结果 通过处方和工艺筛选，选择乳糖作为赋形剂，最优处方赋形剂用量为每瓶90 mg，最优成盐pH值为3.7～3.9，中间体pH控制范围在5.0~6.0内无显著性差异，预冻工艺选择先迅速降温至–50℃后再升温至–20℃，继续降温至–50℃的退火程序，2次干燥时间为600 min时产品水分为0.3%，继续延长时间水分不再下降。结论 通过处方和工艺筛选，确定了最优处方工艺。

Abstract:

OBJECTIVE To prepare pirarubicin hydrochloride freeze-dried preparation and investigate the effects of prescription design and freeze-drying process on product quality.METHODS Pirarubicin hydrochloride was prepared by freeze-drying process. The effects of the type and dosage of excipients, pH control of intermediate solution and freeze-drying curve design on related substances or moisture content were investigated. RESULTS The optimal dosage of lactose was 90 mg per bottle, the optimal pH value of salt formation was 3.7-3.9. There was no significant difference in the pH control range of 5.0-6.0 for intermediate. The pre-freezing process was to rapidly reduce the temperature to -50℃, then increase the temperature to -20℃ and continue to cool down to -50℃. When the second drying time was 600 min, the moisture content was 0.3%, and the moisture content would not drop again with longer time of second drying. CONCLUSION The optimal prescription process is determined by screening the prescription and process.