A mixed polymeric micellar formulation of itraconazole: Characteristics, toxicity and pharmacokinetics

A mixed polymeric micelle formulation of itraconazole (ITZ-PM) was prepared using monomethoxy poly(ethylene glycol)-b-poly(lactic acid) and poly(lactic acid) as drug carrier materials. The ITZ-PM formulation remarkably increased the itraconazole solubility up to 15 mg/mL in aqueous media and provided stable solutions at a wide range of concentrations and pH's. In toxicity studies of single and 28-day repeated administrations to rats and dogs, ITZ-PM was well tolerated at dose levels corresponding to clinical doses. The pharmacokinetic profiles of ITZ-PM for itraconazole and its major metabolite, hydroxy-itraconazole, were comparable to those of the cyclodextrin formulations (Sporanox (R) Injection and Oral Solution) in rats and dogs. These results suggest that ITZ-PM can be an advantageous formulation for both intravenous and oral routes. (c) 2006 Elsevier B.V. All rights reserved.