Preparation and Evaluation of Paliperidone Thermal Muco-Adhesive in Situ Gel as a Nasal to Brain Delivery System

Background: Paliperidone PAL is a second-generation (atypical) antipsychotic medication widely used in the treatment of schizophrenia disorders. It is practically insoluble in water (class II) and has a first-pass metabolism, with oral bioavailability of about 28%. Objective: To optimize and evaluate PAL in a nanothermal residence gel as an intranasal in situ gel formula near or at the site of the nasal-brain delivery system. Methods: The previously prepared nanosuspension formula of PAL was introduced into the creation of in-situ gel formulas using Poloxamer 407 (18–20%w/v), hydroxypropyl methylcellulose HPMC K4 (0.5–1%w/v), and hyaluronic acid (0.5–1%w/v). The selected prepared formula was subjected to different in vitro evaluation studies. Results: The previously prepared nanosuspension formula of PAL, which enhanced its dissolution rate using Soluplus® as a stabilizer, was incorporated into mucoadhesive thermal sensitive gel formulas, using poloxamer 407 as a thermal gelling agent and different concentrations of mucoadhesive polymers. The formula NIG, which contains 20% w/w poloxamer 407 and 1%w/w HPMC K4, exhibited favorable and accepted characteristics, including the ideal gelation temperature of 33°C and drug content of 99.96%, gel strength of 55.0 seconds, spreadability of 5.2cm, and 98.0% in vitro cumulative drug release extended for 6 hours in simulated nasal fluid (SNF) at pH 6.5 maintained at 34°C. Conclusions: The current mucoadhesive in situ gel PAL formula is a promising nasal-to-brain formula that can be used for the management of psychotic disorders drug therapy in the future.