Self-emulsifying bifendate pellets: preparation, characterization and oral bioavailability in rats.
In this study, a self-emulsifying pellet (SEP) was prepared in order to improve the bioavailability of bifendate (DDB). First, a liquid self-emulsifying drug delivery system (SEDDS) was formulated, and then further developed into the SEP by extrusion/spheronization technology using the reconstituted emulsion as the adhesive. The optimized liquid SEDDS consisted of Miglycol(®) 840, a mixture of Cremorphor(®) EL and Solutol HS(®) 15 (1:2, w/w), and Transcutol HP as the oil phase, the surfactant and the co-surfactant at a weight ratio of 40:45:15 (w/w/w), respectively. The SEP were prepared using a mixture of MCC, lactose, and mannitol (45:45:10, w/w/w) as solid adsorbents. The SEP with 40% (w/w) of the liquid SEDDS was round-shaped with a uniform size (800-1000 µm). There was no difference in droplet size between the emulsions obtained from the liquid SEDDS or the SEP (169.8 ± 6.3 nm and 163.7 ± 3.8 nm). Compared with that of DDB pills (less than 20%), in vitro release of DDB from the SEP (over 80% within 60 min) was significantly enhanced in 0.1N HCl, although slower than that of the liquid SEDDS (over 80% within 5 min). AUC of DDB of the SEP after oral administration in rats exhibited 2.36-fold greater than that of DDB pills and no significant difference compared with that of the liquid SEDDS. In conclusion, our studies illustrated that extrusion/spheronization technique could be a useful method to prepare this SEP and it could be a promising way for enhancing oral bioavailability of poorly water-soluble drugs.
Department of Pharmacy, China Pharmaceutical University, Nanjing, PR China.
Yanyu
Y
Xiao
Shan
S
Wang
Yinan
Y
Chen
Qineng
Q
Ping
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D001682:Biological Availability; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D004343:Drug Implants; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004655:Emulsions / Q000737:chemistry* / Q000493:pharmacokinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D001713:Biphenyl Compounds; D004343:Drug Implants; D004365:Drugs, Chinese Herbal; D004655:Emulsions; C465548:bifendate