title: Preparation, characterization and in vivo studies of amorphous solid dispersion of berberine with hydrogenated phosphatidylcholine.
abstract: Berberine, a pure crystalline quaternary ammonium salt with the basic structure of isoquinoline alkaloid, has multiple pharmacological bioactivities. But the poor bioavailability of berberine limited its wide clinical applications. In the present study, we aimed to develop an amorphous solid dispersion of berberine with hydrogenated phosphatidylcholine (HPC) in order to improve its bioavailability. The physical characterization studies such as differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Fourier transform infrared spectrophotometry (FT-IR) and scanning electron microscopy (SEM) were conducted to characterize the formation of amorphous berberine HPC solid dispersion (BHPC-SD). The everted intestinal sac and single-pass intestinal perfusion study proved that permeability and intestinal absorption of amorphous BHPC-SD was improved compared with that of pure crystalline berberine, and the pharmacokinetic study results demonstrated that the extent of bioavailability was significantly increased as well. However, the dissolution study indicated that the aqueous cumulative dissolution percentages of berberine remained unchanged or even lower by means of preparation into solid dispersion with HPC. Therefore, according to the previous mechanistic studies, the present results supported that it is the enhanced molecularly dissolved concentration (supersaturation) of berberine by transformation from crystalline structure into amorphous solid dispersions that triggers the enhanced permeability, and consequently results in the improved intestinal absorption and bioavailability.
authors: Department of Pharmacy, Tongji Hospital affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China; School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Chunyang
authors: C
authors: Shi
authors: Department of Pharmacy, Tongji Hospital affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Qing
authors: Q
authors: Tong
authors: Department of Pharmacy, Tongji Hospital affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Jianguo
authors: J
authors: Fang
authors: Department of Pharmacy, Tongji Hospital affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Chenguang
authors: C
authors: Wang
authors: School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Jizhou
authors: J
authors: Wu
authors: Department of Pharmacy, Tongji Hospital affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China. Electronic address: wangwenqing_tj@163.com.
authors: Wenqing
authors: W
authors: Wang
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D000930:Antidiarrheals / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D001599:Berberine / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D055598:Chemical Phenomena; D003106:Colon / Q000378:metabolism; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D004339:Drug Compounding; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry*; D006207:Half-Life; D006865:Hydrogenation; D007082:Ileum / Q000378:metabolism; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism; D008297:Male; D010713:Phosphatidylcholines / Q000737:chemistry*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013535:Suspensions
chemical_list: D000890:Anti-Infective Agents; D000930:Antidiarrheals; D004337:Drug Carriers; D005079:Excipients; D010713:Phosphatidylcholines; D013535:Suspensions; D001599:Berberine
keywords: Amorphous solid dispersion; Berberine; Bioavailability; Hydrogenated phosphatidylcholine; Intestinal absorption; Permeability