An oral formulation of cilostazol nanoparticles enhances intestinal drug absorption in rats.

Cilostazol (CLZ) is an anti-platelet agent that is generally used after the onset of cerebral infarction. However, CLZ is a poorly water-soluble drug and a strategy for increasing its bioavailability is required. In the present study, novel oral formulations were designed containing CLZ solid nanoparticles to improve bioavailability. The present study investigated the therapeutic effect of the oral formulations containing CLZ nanoparticles on ischemic stroke using a cerebral ischemia/reperfusion-induced injury model (MCAO/reperfusion mice). The oral formulation containing CLZ nanoparticles (CLZ/R(nano) tablet) was prepared using a combination of recrystallization and ball milling with the following ingredients: CLZ, docusate sodium, methylcellulose, 2-hydoxypropyl-β-cyclodextrin, gum arabic, polyvinylpyrrolidone, and mannitol. The particle size after re-dispersion of the CLZ/R(nano) tablet was 64±47 nm (mean ± standard deviation). The CLZ areas under the concentration-time curve (AUC) and mean residence time (MRT) in rats that were administered CLZ/R(nano) tablets were significantly greater compared with those in rats that were administered CLZ/R(micro) tablets. Results indicated, the AUC after administration of CLZ/R(nano) tablets was 3.1-fold higher compared with that after administration of the commercially available CLZ OD tablet. In addition, oral administration with CLZ/R(nano) tablets ameliorated neurological deficits caused by ischemic stroke in MCAO/reperfusion mice. It is possible that the oral formulation containing CLZ nanoparticles will be useful for the treatment of patients with ischemic stroke and that these findings will provide significant information that can be used to improve the drug with low bioavailability.