Preparation, characterization, and pharmacokinetics of sterically stabilized nimodipine-containing liposomes.
Nimodipine is a dihydropyridine calcium antagonist used in clinical trials in the treatment of ischemic damage in subarachnoid hemorrhage and commercially available as nimotop intravenous infusion solution and tablets. However, due to its poor solubility in water, intravenous administration depends on the use of the dehydrated alcohol to achieve a clinically relevant concentrated infusion solution while the low bioavailability of the nimotop tablets were far away from content. We have prepared a well-characterized novel lyophilized liposome-based nimodipine formulation that is sterile and easy-to-use. Of the several formulations examined, nimodipine-liposomes composed of ePC/CHOL 20:3 and co-surfactant poloxamer 188/sodium deoxycholate/ePC/3:0.3:5 were chosen for further studies. This composition was found to give more stable liposomes than other formulations. It gave 89.9% entrapment efficiency and particle size of 200 nm after lyophilization. The pharmacokinetic parameters following orally and intravenously administration to New Zealand rabbits were determined and compared with those of commercial nimodipine formulations. Encapsulation of nimodipine in liposomes produced marked differences over those of commercial preparations with an increased C(max), prolonged elimination half-life, and an increased value for AUC. The obtained values for mean residence time (MRT) indicated that nimodipine remains longer for liposomal formulation. Thus an optimum i.v. liposome formulation for nimodipine can be developed for an alternative to the commercial nimodipine preparations.
Department of Pharmaceutics, College of Pharmacy, China Pharmaceutical University, Tong Jiaxiang 24, Nanjing 210009, P.R. China. jiabi_zhu@hotmail.com
Danbo
D
Yang
Jiabi
J
Zhu
Ying
Y
Zheng
Liang
L
Ge
Guifang
G
Zhang
D000818:Animals; D019540:Area Under Curve; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D002784:Cholesterol / Q000737:chemistry; D004355:Drug Stability; D005612:Freeze Drying; D006207:Half-Life; D007262:Infusions, Intravenous; D008081:Liposomes; D008657:Metabolic Clearance Rate; D009553:Nimodipine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D011817:Rabbits
D002121:Calcium Channel Blockers; D008081:Liposomes; D010713:Phosphatidylcholines; D009553:Nimodipine; D002784:Cholesterol