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Olanzapine (OLA), a first atypical antipsychotic moleculethat experiences low brain permeability because of efflux by P-glycoproteins (Pgp) in the brain and extensive hepatic first-pass metabolism. The present investigation intended to design OLA-loaded mixed micelles (MM) and study their nose-to-brain targeting capability. OLA-MM was prepared by a mixture of d-α-tocopheryl polyethylene glycol 1000 succinate and gelucire®44/14 (stearoylmacrogol glycerides) (OLA-TPGL-MM) using the solvent evaporation technique. OLA-TPGL-MM was studied for various physiochemical properties, in-vitro release, ex-vivodrug permeation and in-vivo pharmacokinetic potential in male Wister rats as compared to OLA alone. Developed OLA-TPGL-MM showed particle size, negative zeta potential and entrapment efficiency of 125 nm, −5.97 mV and &gt; 83%, respectively. OLA-TPGL-MM showed 2.12 and 1.85-fold improvement in in-vitro and ex-vivo OLA release and permeation. Substantially higher values for intranasal (i.n) OLA-TPGL-MM in drug targeting efficiency (265.36%), drug targeting index (1.82) and direct transport percentage (64.36%) indicating the potential of non-invasive OLA-loaded MM nose-to-brain targeting delivery system. TheTPGS and gelucire®44/14 based MM has a great potential for the safe and effective delivery of antipsychotic molecules in the treatment of CNS disorders.

materials technology

D-α-Tocopherol polyethylene glycol succinate and stearoylmacrogol glycerides biomaterial based nanostructured mixed micelles as nose-to-brain targeting drug delivery system