纳米多孔花形乳糖装载姜黄素干粉吸入剂的制备及体外释药性能研究  

Preparation and in vitro Release Property Study of Curcumin Dry Powder Inhalation Loaded by Nanoporous Flower-shaped Lactose

作　　者：李楠[1] 李旭[1] 程鹏[1] 孔令钰[1] 冯仁蕊[1] 谭淞文 LI Nan;LI Xu;CHENG Peng;KONG Lingyu;FENG Renrui;TAN Songwen(Tianjin Institute of Pharmaceutical Science,Tianjin 300020,China;Xiangya School of Pharmaceutical Sciences,Central South University,Changsha 410013,China)

机构地区：[1]天津市医药科学研究所,天津300020 [2]中南大学湘雅药学院,长沙410013

出　　处：《中国药房》2021年第7期794-801,共8页China Pharmacy

基　　金：国家自然科学基金资助项目(No.81903565);天津市自然科学基金资助项目(No.18JCQNJC13500);天津市卫生健康科技人才培育项目(No.KJ20079)。

摘　　要：目的:制备一种新型的纳米多孔花形乳糖(FL)装载姜黄素(Cur)干粉吸入剂(DPI),为难溶性药物治疗慢性阻塞性肺疾病提供一种安全、高效的肺内递药方式。方法:采用溶液吸附法制备FL微粒装载Cur(Cur-FL)复合粉末。以载药量和吸附率为指标,通过单因素试验优选Cur投药浓度、Cur与FL的投药比例(m/m)和吸附时间,以确定Cur-FL复合粉末的最佳制备工艺。采用傅里叶变换红外光谱、扫描电子显微镜、差示扫描量热法等技术对以最优工艺制备的Cur-FL复合粉末的理化性质进行表征;测定其含水量并考察其空气动力学性质;通过体外模拟人工肺液环境,探讨其体外释药行为。结果:Cur-FL复合粉末的最佳制备工艺为Cur投药浓度5 mg/mL、Cur与FL的投药比例1∶4、吸附时间1 h。所得复合粉末的载药量为(23.37±0.43)%、包封率为(91.64±0.44)%、吸附率为(30.50±0.72)%。Cur-FL微粒呈花形外观;Cur被物理吸附在FL微粒孔隙内,未发生化学变化。Cur-FL复合粉末的松密度为(0.21±0.02)g/cm^(3)、振实密度为(0.33±0.01)g/cm^(3)、休止角为(24.07±0.31)°、平均粒径为(3.96±0.80)μm、空气动力学粒径为(3.33±0.99)μm、含水量为(5.63±0.24)%、排空率为(92.53±0.87)%、体外有效部位沉积率为(45.93±1.77)%;其在人工肺液中的24 h溶解度[(358.93±1.67)μg/mL]为Cur的3.28倍、48 h累积体外释放率(90.21%)为Cur的1.63倍,而Cur+FL物理混合物不能提高Cur在人工肺液中的溶解度和释放度。结论:所制Cur-FL复合粉末的体外释药性能较好,且其粉体学性质、溶解性、水分、流动性及空气动力学性能等均符合《中国药典》对DPI的要求。OBJECTIVE:To preparea novel Curcumin(Cur)dry powder inhalation(DPI)loaded by nanoporous flower-shaped lactose(FL),and to provide a safe and effective intrapulmonary drug delivery method for the therapy of chronic obstructive pulmonary disease with insoluble drugs.METHODS:FL-loaded Cur(Cur-FL)compound powder was prepared by solution adsorption method.Using drug-loading amount and adsorption rate as indicators,single-factor experiment was used to optimize Cur concentration,Cur-FL ratio(m/m)and adsorption time so as to determine the optimal preparation technology for Cur-FL compound powder.Fourier transform infrared spectroscopy,scanning electron microscope and differential scanning calorimetry were used to characterize the physical and chemical properties of Cur-FL compound powder prepared with optimal technology.The water content and aerodynamic properties were determined;in vitro drug release behavior was investigated by simulating the environment of artificial lung fluid.RESULTS:The optimal preparation technology of Cur-FL compound powder was Cur concentration of 5 mg/mL,Cur-FL ratio of 1∶4,adsorption time of 1 h.The drug-loading amount of compound powder was(23.37±0.43)%,the encapsulation rate was(91.64±0.44)%,and the adsorption rate was(30.50±0.72)%.Cur-FL particles were flower shaped;Cur was physically adsorbed in the pores of FL without chemical changes.The bulk density of Cur-FL compound was(0.21±0.02)g/cm^(3),tap density was(0.33±0.01)g/cm^(3),angle of repose was(24.07±0.31)°,average particle size was(3.96±0.80)μm,aerodynamic particle size was(3.33±0.99)μm,water content was(5.63±0.24)%,emptying rate was(92.53±0.87)%,and deposition rate of effective parts in vitro was(45.93±1.77)%.Its 24 h solubility in artificial lung fluid([358.93±1.67)μg/mL]were 3.28 times of Cur,48 h cumulative release ratesin in vitro(90.21%)were 1.63 times of Cur,but Cur+FL physical mixture could not improve the solubility and release of Cur in artificial lung fluid.CONCLUSIONS:Cur-FL compound powder has good in vitr

关 键 词：姜黄素 花形乳糖 干粉吸入剂 制备 体外释药 

分 类 号：R943[医药卫生—药剂学]