Lipotomes were designed to enhance lacidipine's oral bioavailability by improving its solubility and enhancing the oral lymphatic uptake. Lipotomes were prepared using cetyl alcohol and Tween(®) 80 using a thin film hydration technique. Cetyl alcohol was chosen for imparting a lipophilic environment that would enforce the lymphatic uptake while Tween(®) 80 would improve drug solubility within the lipotomes. Lipotomes were characterized by analyzing their particle size, solubilization efficiency and in-vitro drug release. Central composite design was applied to statistically optimize the formulations using Design-Expert(®) software. The optimum formula (OLT) was made up of excipients:drug ratio of 36.59:1 w/w and Tween(®) 80:cetyl alcohol ratio of 4:1 w/w. OLT was lyophilized and filled into Eudragit(®) L100 enteric coated capsules. Mannitol (10% w/v) was the ideal cryoprotectant to retain the physicochemical characteristics of the OLT formulation after lyophilization. In conclusion, the selected lyophilized formula (L3) succeeded in enhancing drug's oral bioavailability in human volunteers compared to the commercial product confirming the success of lipotomes as a novel oral nanocarrier for insoluble drugs having extensive first pass metabolism.
Keywords: Central composite; Enteric coating; Lacidipine; Lipotomes; Lyophilization.
Copyright © 2014 Elsevier B.V. All rights reserved.