Study on Preparation Phase Identification and Release Rate in vitro of Inclusion Compound of Indapamide- β-cyclodextrin Inclusion Compound
- VernacularTitle: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
- Author:
Meijia SONG
1
;
Jingtian HAN
1
;
Baocheng TIAN
1
Author Information
1. College of Pharmacy,Binzhou Medical University,Shandong Yantai 264003,China
- Publication Type:Journal Article
- Keywords:
Indapamide;
β-cyclodextrin;
Inclusion compound;
Technology optimization;
Phase identification;
in vitro release rate
- From:
China Pharmacy
2019;30(12):1608-1612
- CountryChina
- Language:Chinese
-
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.