Preparation and in vitro/ex vivo evaluation of nanoemulsion for transnasal delivery of paliperidone

Paliperidone was formulated in mucoadhesive nanoemulsion with the aim of improving its solubility and transnasal delivery, which can further utilized for its preclinical evaluation. Solubility of Paliperidone in oils, emulsifiers, co-emulsifiers was determined to identify nanoemulsion components. Emulsifier and co-emulsifiers were screened for their ability to emulsify selected oily phase. Phase diagrams were constructed to identify the area of nanoemulsification. Paliperidone nanoemulsion was formulated using spontaneous nanoemulsification method. The three nanoemulsions (PMNE4, PMNE5, and PMNE6) containing 5.71-6.80 % oleic acid as an oily phase, 47.62-51.63 % labrasol and plurol oleique CC 497 as emulsifier mixture (1:1), 42.86-45.58 % (wt/wt) aqueous phase having a suitable optical transparency of 98.33-99.33 %, globule size of 28.8-43.2 nm and polydispersity of 0.129-0.152 were selected for the incorporation of mucoadhesive polymer. The PMNE6 showed highest flux (5.072 +/- 0.13 mu g/cm(2)/min) with enhancement ratio of 1.1 as compared to Paliperidone solution (PS). The diffusion co-efficient of PMNE6 was significantly higher than PMNE5, PMNE4 and PS and followed higuchi model. The formulation was found to be free from nasal cilio toxicity. All formulations were found to be stable for 6 months at room temperature.