title: Preparation and characterization of micronized ellagic acid using antisolvent precipitation for oral delivery.
abstract: In this work, poorly water soluble phytochemical ellagic acid (EA) was micronized to increase its solubility and thereby the bioavailability during antisolvent precipitation process using N-methyl pyrrolidone (NMP) as solvent and deionized water as antisolvent. The micronized EA (m-EA) freeze-dried powder was prepared by the subsequent lyophilization process. The effects of various experimental parameters on the mean particle size (MPS) of m-EA suspension (m-EAS) in the antisolvent precipitation process were investigated. MPS and production efficiency were taken into account comprehensively to obtain the optimum conditions of antisolvent precipitation. Under the optimum conditions, m-EA freeze-dried powder with a MPS of 429.2 ± 7.6 nm was obtained. The physico-chemical properties of m-EA freeze-dried powder were detected by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), liquid chromatography-tandem mass spectrometry (LC-MS/MS), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The results indicated m-EA kept the same chemical structure with raw EA, but the crystallinity was greatly reduced. Furthermore, a comparison of the 50% inhibition concentration (IC50) values revealed that m-EA was more effective than raw EA in scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. Meanwhile, m-EA also showed higher reducing power. Moreover, the residual amount of NMP was lower than the International Conference on Harmonization limit (530 ppm) for solvents. The dissolution rate of m-EA was approximately 2 times of raw EA. Moreover, the solubility of m-EA was about 6.5 times of raw EA. Meanwhile, the bioavailability of m-EA increased about 2 times compared with raw EA via oral administration.
authors.affiliation: Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin 150040, Heilongjiang, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin 150040, Heilongjiang, China. Electronic address: xiuhuazhao@nefu.edu.cn.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin 150040, Heilongjiang, China. Electronic address: yuangangzu@163.com.
authors.forename: Yuangang
authors.initials: Y
authors.lastname: Zu
authors.affiliation: Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin 150040, Heilongjiang, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin 150040, Heilongjiang, China.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Ge
authors.affiliation: Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin 150040, Heilongjiang, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhong
authors.affiliation: Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin 150040, Heilongjiang, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D011232:Chemical Precipitation; D003451:Cryoprotective Agents / Q000737:chemistry; D004339:Drug Compounding; D004610:Ellagic Acid / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D005612:Freeze Drying; D008297:Male; D011134:Polysaccharides / Q000737:chemistry; D011760:Pyrrolidinones / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D012995:Solubility; D012997:Solvents / Q000737:chemistry
chemical_list: D003451:Cryoprotective Agents; D011134:Polysaccharides; D011760:Pyrrolidinones; D012997:Solvents; D004610:Ellagic Acid; C008315:maltodextrin; C038678:N-methylpyrrolidone
keywords: Antioxidant activity; Antisolvent precipitation; Bioavailability; Dissolution rate; Ellagic acid