title: Preparation of inclusion complex of apigenin-hydroxypropyl-β-cyclodextrin by using supercritical antisolvent process for dissolution and bioavailability enhancement.
abstract: In this study, an inclusion complex of apigenin (AP)-hydroxypropyl-β-cyclodextrin (HP-β-CD) was prepared via supercritical antisolvent (SAS) method using N, N-dimethylformamide (DMF) as solvent and carbon dioxide as antisolvent. The mole ratio of AP and HP-β-CD (1:1) was established by phase solubility equilibrium experiment. The optimal conditions were determined through single-factor experiments; these conditions included precipitation pressure of 22.5MPa, precipitation temperature of 50°C, and AP concentration of 20mg/ml. The load efficiency and encapsulation efficiency of the AP-HP-β-CD inclusion complex, with a mean particle size of 392.13±7.56nm, were 13.97%±0.17% and 93.22%±1.17%, respectively, under the optimal conditions. FTIR, (1)H NMR, SEM, XRD, DSC, and TG analyses were also conducted. Results showed that the inclusion complex was formed because of the interaction between AP and HP-β-CD. DMF residue in the inclusion complex was 0.033% lower than the ICH limit for class II solvents. The solubility of the inclusion complex was approximately 152.43 times higher than that of the raw AP. In the in vitro study, the dissolution rate of the AP-HP-β-CD inclusion complex was about 7.60 times higher than that of the raw AP. In the in vivo study, the bioavailability of the inclusion complex increased by 6.45 times compared with that of the raw AP. Hence, the prepared AP-HP-β-CD inclusion complex exhibits potential as a new oral therapeutic agent formulation for clinical applications.
authors: Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin, Heilongjiang 150040, China.
authors: Yannian
authors: Y
authors: Huang
authors: Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin, Heilongjiang 150040, China.
authors: Yuangang
authors: Y
authors: Zu
authors: Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin, Heilongjiang 150040, China. Electronic address: xiuhuazhao@nefu.edu.cn.
authors: Xiuhua
authors: X
authors: Zhao
authors: Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin, Heilongjiang 150040, China.
authors: Mingfang
authors: M
authors: Wu
authors: Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin, Heilongjiang 150040, China.
authors: Ziqi
authors: Z
authors: Feng
authors: Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin, Heilongjiang 150040, China.
authors: Yiping
authors: Y
authors: Deng
authors: Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin, Heilongjiang 150040, China.
authors: Chang
authors: C
authors: Zu
authors: Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin, Heilongjiang 150040, China.
authors: Lingling
authors: L
authors: Wang
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D047310:Apigenin / Q000097:blood* / Q000138:chemical synthesis* / Q000494:pharmacology; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D025924:Chromatography, Supercritical Fluid / Q000379:methods*; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D012997:Solvents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D047392:beta-Cyclodextrins / Q000097:blood* / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D012997:Solvents; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D047310:Apigenin
keywords: Apigenin; Bioavailability; Dissolution; Hydroxypropyl-β-cyclodextrin; Inclusion complex; Supercritical antisolvent method