In situ niosome forming maltodextrin proniosomes of candesartan cilexetil: In vitro and in vivo evaluations

The aim of this study is to develop novel proniosomal tablets of candesartan cilexetil. Drug loaded proniosomes were prepared as dry powder by slurry method. The critical parameters of the production process were the type of the carrier (sorbitol, maltodextrin, and lactose), addition of charge inducers, rotation speed of the rotavapor and solvent evaporation temperature. The effects of these parameters on proniosome specifications such as the recovery, drug loading, drug release were investigated and also the influence on the particle size and surface charge of the niosomes derived by the hydration of proniosomes were evaluated. The mean particle size and drug loading of niosomes formed from the hydrated proniosomes were 204 ± 2 nm and 99.09 ± 0.04% respectively, with a negative charge −43.65 ± 0.54 mV. The proniosomes demonstrated good flowability, compressibility and consolidation properties both alone and together with the tableting agents (microcrystalline cellulose and cross-linked poly vinylpyrrolidone). The niosomes derived by the hydration of proniosomal tablets preserved their initial properties. Compatibly with the increased in vitro drug dissolution rate, the relative bioavailability of drug from proniosomal tablets increased 1.86-fold and 2.75-fold and higher candesartan plasma levels were achieved within shorter time compared to the pure drug.