LAUSR

Abstract Epilepsy is one of the most common neurological disorders in the world. The therapeutic treatment is challenging since conventional drugs have limited efficacy and several side effects that impair patient management. Efforts are being made to find innovative strategies to control epileptic seizures. Intranasal administration provides a convenient route to deliver the drug to the brain. Carbamazepine (CBZ) is an anticonvulsant characterized by poor water solubility, nanonization can improve its bioavailability. Therefore, the design of CBZ nanocrystals (NCs) was assessed to obtain a formulation suitable for nose-to-brain delivery. CBZ NCs were prepared by sonoprecipitation following the Quality by Design approach identifying the impact of process and formulation variables on the critical quality attributes of the final product. The formulation was characterized by a technological point of view (thermotropic behavior, crystallinity, morphology, mucoadhesive strength). Response surface methodology was a reliable tool (error % 2.6) to optimize CBZ NCs with size ≤300 nm. Incubation of CBZ NCs in artificial cerebrospinal fluid at 37 °C did not promote aggregation and degradation phenomena. Preliminary biological studies revealed the biocompatibility of CBZ NCs towards Olfactory Ensheating Cells. The suspension was successfully converted into a powder. The highly concentrated formulation can be obtained, providing the possibility to administer the maximum dose of the drug in the lowest volume. Graphical Abstract