吲达帕胺-β-环糊精包合物的制备、物相鉴定及体外释放度研究
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篇名: 吲达帕胺-β-环糊精包合物的制备、物相鉴定及体外释放度研究
TITLE:
摘要: 目的:建立吲达帕胺(IDP)-β-环糊精(β-CD)包合物的含量测定方法并优化其制备工艺,对所制包合物进行物相鉴定及体外释放度考察。方法:采用紫外分光光度法测定IDP-β-CD包合物中IDP的含量;采用溶液-搅拌法制备IDP-β-CD包合物,以包合率为考察指标,采用正交试验优化制备工艺;比较不同干燥法对包合率和载药率的影响;采用红外光谱分析(IR)法和差式扫描量热法(DSC)对IDP-β-CD包合物进行物相鉴定;通过体外释放度试验考察不同干燥法对IDP-β-CD包合物释放行为的影响。结果:IDP的检测质量浓度线性范围为2.0~14.0 μg/mL(r=0.999 7);定量限、检测限分别为0.204、0.067 μg/mL;精密度、稳定性、重复性试验的RSD均小于2%;加样回收率为98.8%~101.8%(RSD=1.10%,n=6)。最优制备工艺为β-CD与IDP摩尔比为3 ∶ 1,包合时间为3 h,搅拌速度为300 r/min;所得包合物的平均包合率为72.81%。IR和DSC分析结果均显示,IDP与β-CD通过物理作用形成包合物。经喷雾干燥后,IDP-β-CD包合物的包合率为(60.96±0.25)%、载药率为(4.18±0.12)%;经冷冻干燥后,其包合率为(77.31±0.51)%、载药率为(5.31±0.27)%。12 h内,IDP 原料药、IDP-β-CD包合物(分别经冷冻干燥和喷雾干燥制备)的累积释放度分别为37.2%、42.5%、81.9%;与IDP 原料药相比,喷雾干燥所得IDP-β-CD包合物的累积释放度升高更为明显。结论:所建含量测定方法简便、准确;优化的包合物制备工艺稳定、可行,成功制得IDP-β-CD包合物,且喷雾干燥法可获得释放度更高的包合物。
ABSTRACT: OBJECTIVE: To establish a method for content determination of indapamide (IDP)-β-cyclodextrin (β-CD) inclusion compound, optimize the preparation technology, carry out phase identification and in vivo release study of it. METHODS: UV spectrophotometry was used to determine the content of IDP in IDP-β-CD inclusion compound. IDP-β-CD inclusion compound was prepared by the solution-stirring method and the preparation technology was optimized by the orthogonal experiment using inclusion rate as index. The inclusion rate and drug-loading rate were compared between different drying methods. Phase identification of IDP-β-CD inclusion compound was verified by IR and DSC. The cumulative release rate of inclusion compound was tested by in vitro experiment. RESULTS: The linear range of concentration of IDP was 2.0-14.0 μg/mL (r=0.999 7). The quantitative limit and detection limit were 0.204, 0.067 μg/mL, respectively. RSDs of precision, stability and repeatability tests were all less than 2%. The recoveries range was 98.8%-101.8%(RSD=1.10%,n=6). The optimum technology conditions were as follows the molar ratio of β-CD to IDP was 3 ∶ 1, the inclusion time was 3 h, and the stirring speed was 300 r/min. Average inclusion rate of IDP-β-CD inclusion compound was 72.81%. IR and DSC analysis showed that IDP and β-CD formed inclusion compound through physical interaction. After spray drying, the inclusion rate and drug-loading rate of IDP-β-CD inclusion compound were (60.96±0.25)% and (4.18±0.12)%. After freeze-drying, the inclusion rate and drug-loading rate of IDP-β-CD inclusion compound were (77.31±0.51)% and (5.31±0.27)%. Accumulative release rates of IDP, IDP-β-CD inclusion compound (by freeze-drying and spray drying) were 37.2%, 42.5% and 81.9% within 12 h, respectively. Compared with IDP raw material, accumulative release rate of IDP-β-CD inclusion compound increased significantly after spray drying. CONCLUSIONS: Established method is simple and accurate. The optimal preparation technology of inclusion compound is stable and feasible. IDP-β-CD inclusion compound is prepared successfully. The inclusion compound prepared by spray drying shows higher release rate.
期刊: 2019年第30卷第12期
作者: 宋美佳,韩景田,田宝成
AUTHORS: SONG Meijia,HAN Jingtian,TIAN Baocheng
关键字: 吲达帕胺;β-环糊精;包合物;工艺优化;物相鉴定;体外释放
KEYWORDS: Indapamide; β-cyclodextrin; Inclusion compound; Technology optimization; Phase identification; in vitro release rate
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