Nimodipine-loaded mixed micelles: formulation, compatibility, pharmacokinetics, and vascular irritability study.
BACKGROUND
The clinical application of nimodipine (NIM) is limited by several unfavorable properties, which are induced by its low aqueous solubility. In the present study, nimodipine-loaded egg phosphatidylcholine-sodium glycocholate mixed micelles (NIM-EPC-SGC-MMs) were prepared to improve the water solubility of NIM, thus allowing it to be more applicable for clinical use.


METHODS
NIM-EPC-SGC-MMs were prepared using the coprecipitation method and the factors influencing formulation quality were optimized. After formulation, water solubility, solubilizing efficiency, drug loading, particle size, physical compatibility, pharmacokinetics, and vascular irritability were determined.


RESULTS
The mean size of the NIM-EPC-SGC-MMs was 6.099 ± 0.048 nm under optimized conditions. The water solubility of NIM in EPC-SGC-MMs was enhanced 250-fold compared with free NIM. The physical compatibility, pharmacokinetic, and vascular irritability studies showed that, in comparison to the commercially available NIM injections, NIM-EPC-SGC-MMs presented better physical compatibility, the same pharmacokinetic profile, and less risk of local vascular irritation and phlebitis.


CONCLUSIONS
EPC-SGC-MMs represent a promising new formulation suitable for the intravenous delivery of NIM.
Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu.
Xu
X
Song
Yu
Y
Jiang
Chunjuan
C
Ren
Xun
X
Sun
Qiang
Q
Zhang
Tao
T
Gong
Zhirong
Z
Zhang
D000818:Animals; D004355:Drug Stability; D004423:Ear / Q000098:blood supply; D004487:Edema / Q000139:chemically induced; D006000:Glycocholic Acid / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D006863:Hydrogen-Ion Concentration; D008297:Male; D008823:Micelles; D009553:Nimodipine / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000633:toxicity; D010316:Particle Size; D010689:Phlebitis / Q000139:chemically induced; D010713:Phosphatidylcholines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D014680:Veins / Q000187:drug effects
D008823:Micelles; D010713:Phosphatidylcholines; D009553:Nimodipine; D006000:Glycocholic Acid