姜黄素固体脂质纳米粒干粉吸入剂的质量评价及初步稳定性考察

Quality Evaluation and Preliminary Stability Study of Curcumin Solid Lipid Nanoparticles Powder Inhalation

目的:对姜黄素(Cur)固体脂质纳米粒(SLN)干粉吸入剂(DPI)进行质量评价及初步稳定性考察。方法:按《中国药典》相关要求对粉末的理化性质[粒径、溶解性、引湿性及临界相对湿度、流动性(休止角)、水分等]及制剂质量评价指标(主药含量均匀度、排空率和体外有效部位沉积率)进行考察;对制剂进行初步的稳定性试验(加速试验、长期试验和影响因素试验)。结果:3批Cur-SLN-DPI各指标的平均值分别为粒径3.35μm、30 s内完全溶解、临界相对湿度70%、休止角24.03°、水分4.57%、主药含量100.13%、含量均匀度3.647、排空率95.17%、体外有效部位沉积率28.73%。加速试验放置3个月后,排空率低于90%,体外有效部位沉积率下降约5%。长期试验中观察期内各指标无明显变化。影响因素试验中,在相对湿度为75%的条件下放置10 d,体外有效部位沉积率下降5%;在相对湿度为92.5%条件下放置5 d,制剂胶囊软化且增质量超过5%。结论:本品质量符合DPI的相关要求;在光照及高温条件下稳定,但在湿热条件下不够稳定,故应贮存于密闭干燥容器中。

OBJECTIVE：To evaluate the quality of Curcumin（Cur） solid lipid nanoparticles（SLN） dry powder inhalation（Cur-SLN-DPI）and investigate its preliminary stability.METHODS：According to related requirements of Chinese Pharmacopeia,physical and chemical properties [particle size,solubility,hygroscopicity,critical relative moisture,mobility（repose angle）,water content] and quality evaluation index（main component content uniformity,emptying rate and in vitro effective part deposition rate） of powder were investigated.Preliminary stability test of pharmaceutical preparation was conducted,including accelerated test,long-term test and influential factor test.RESULTS：Average value of each index in 3 batches of Cur-SLN-DPI as follows as particle size of 3.35 μm,completely dissolved within 30 s,critical relative humidity of 70%,repose angle of 24.03 °,water content of 4.57%,main component of 100.13%,content uniformity of 3.647,emptying rate of 95.17%,in vitro effective part deposition rate of 28.73%.In accelerated test,after placing for 3 months,emptying rate was below 90% and in vitro effective part deposition rate decreased by about 5%.In long-term trial,each index had no significant change during observation period.In influential factor test,under relative humidity（RH）of 75% for 10 d,in vitro effective part deposition rate decreased by 5%;under RH of92.5% for 5 d,capsules were softened and weight gain was more than 5%.CONCLUSIONS：The quality of Cur-SLN-DPI is up to related requirement of DPI;Cur-SLN-DPI keeps stable under light and high temperature condition,but can not keep stable under damp and heat condition.Cur-SLN-DPI should be stored in dry closed container.