Solid self-emulsifying nitrendipine pellets: preparation and in vitro/in vivo evaluation.
Objective of this study is to develop and evaluate the new solid self-emulsifying (SE) pellets of poorly soluble nitrendipine (NTD). These pellets were prepared via extrusion/spheronization technique, using liquid SEDDS (NTD, Miglyol 812, Cremophor RH 40, Tween 80, and Transcutol P), adsorbents (silicon dioxide and crospovidone), microcrystalline cellulose and lactose. The resulting SE pellets with 30% liquid SEDDS exhibited uniform size (800-1000 microm) and round shape, droplet size distribution following self-emulsification was nearly same to the liquid SEDDS (72+/-16 nm and 64+/-12 nm). The in vitro release was similar for the two SE formulations (over 80% within 30 min), both significantly higher than the conventional tablets (only 35% within 30 min). The oral bioavailability was evaluated for the SE pellets, liquid SEDDS and conventional tablets in fasted beagle dogs. AUC of NTD from the SE pellets showed 1.6-fold greater than the conventional tablets and no significant difference compared with the liquid SEDDS. In conclusion, our studies illustrated that extrusion/spheronization technique could be a useful large-scale producing method to prepare the solid SE pellets from liquid SEDDS, which can improve oral absorption of NTD, nearly equivalent to the liquid SEDDS, but better in the formulation stability, drugs leakage and precipitation, etc.
Wang
Zhiyuan
Z
Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No 103 of Wenhua Road, Shenyang 110016, China.
Sun
Jin
J
Wang
Yongjun
Y
Liu
Xiaohong
X
Liu
Yanhua
Y
Fu
Qiang
Q
Meng
Ping
P
He
Zhonggui
Z
D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004343:Drug Implants; D045703:Emulsifying Agents / Q000097:blood* / Q000138:chemical synthesis*; D008297:Male; D009568:Nitrendipine / Q000097:blood* / Q000138:chemical synthesis*; D010865:Pilot Projects
D004343:Drug Implants; D045703:Emulsifying Agents; D009568:Nitrendipine