Preparation, characterization, and pharmacokinetics of sterically stabilized nimodipine-containing liposomes

Drug Development and Industrial Pharmacy
Danbo YangGuifang Zhang

Abstract

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 preparation...Continue Reading

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May 1, 2008·AAPS PharmSciTech·Amit A Kale, Vandana B Patravale
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