Solid dispersion of berberine-phospholipid complex/TPGS 1000/SiO₂: preparation, characterization and in vivo studies.
Berberine (Ber), an isoquinoline alkaloid, arouses wide interests in many researchers in recent years because of its numerous new pharmacological actions. However Ber's low oral bioavailability restricts its wide application. In this study, a solid dispersion (BPTS-SD) composed of berberine-phospholipid complex (BPC), D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS 1000) and SiO₂ was prepared by simple solvent evaporation technique. BPC was employed to improve the liposolubility of Ber, and SiO₂ was used to improve the flowability of BPTS-SD, while TPGS 1000 played a dual role: firstly, as a solid dispersion carrier to improve the dissolution rate of BPC and secondly, as a P-glycoprotein (P-gp) inhibitor to enhance the intestinal absorption of Ber. FTIR, DSC and SEM analysis proved the formation of BPC and BPTS-SD. Po/w of BPC successfully increased from 0.25 to 8.75. In vitro dissolution study showed that the cumulative dissolution percentages of BPTS-SDs were nearly 2.67-4.78-folds of BPC. Single-pass intestinal perfusion studies showed that the absorption of Ber in BPC was increased nearly 1.4-2.0-folds compared to that of Ber which was mainly due to the improved liposolubility, and further increased by BPTS-SD around 0.1-1.3-folds compared to that of BPC through the P-gp inhibition of TPGS 1000. Significant improvements in Cmax and AUC₀→t of BPC and BPTS-SD were obtained in pharmacokinetic study (the highest improvement in oral relative bioavailability of BPTS-SD-1 was 322.66% of Ber). All these results indicated that BPTS-SD can be a promising drug delivery system to improve their oral bioavailability for the Ber's analogues. In particular this solid dispersion can be prepared just by a simple method and has a strong feasibility for industrialization.
Key Laboratory of New Drug Delivery System of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing 210029, PR China; Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, PR China.
Zhenhai
Z
Zhang
Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, PR China.
Yan
Y
Chen
Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, PR China.
Jin
J
Deng
Key Laboratory of New Drug Delivery System of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing 210029, PR China.
Xiaobin
X
Jia
Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, PR China.
Jianping
J
Zhou
Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, PR China. Electronic address: lvhuixia@163.com.
Huixia
H
Lv
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001599:Berberine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004304:Dosage Forms; D004337:Drug Carriers; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008297:Male; D008855:Microscopy, Electron, Scanning; D010743:Phospholipids / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004304:Dosage Forms; D004337:Drug Carriers; D010743:Phospholipids; D001599:Berberine; D014810:Vitamin E; D011092:Polyethylene Glycols; D012822:Silicon Dioxide; C014225:tocophersolan
Berberine; P-glycoprotein; Phospholipid-complex; Silica; Solid dispersions; TPGS 1000