Microemulsion for nasal delivery of Asenapine maleate in treatment of schizophrenia: formulation considerations

The objective of this study was to develop and evaluate the microemulsion (ME) and mucoadhesive microemulsion (MME) for intranasal delivery of Asenapine maleate (APM) for the treatment of schizophrenia. APM loaded ME (AME1 to AME5) and MME (AMME) were prepared by spontaneous microemulsification method and evaluated for drug content, globule size and polydispersity index, % transmittance, zeta potential, pH, viscosity, conductivity, drug content, refractive index, ex vivo diffusion study using sheep nasal mucosa, nasal ciliotoxicity study and Fourier transform infrared spectroscopy study. The AME4 (5 mg/mL of APM) containing 11% Capmul MCM, 38% Smix (Tween80: Propylene glycol (1:1)) and 51% (v/v) water that displayed optical transparency of 99.77%, globule size of 79.50 nm, polydispersity index (PDI) of 0.356 were selected for preparation of MME. The highest diffusion coefficient (P < 0.05) was found for AMME (2.61 × 10−5 ± 0.016 × 10−5 cm2/min) and followed higuchi model. The nasal ciliotoxicity study showed no damage to nasal mucosa and thus the formulation components were considered biocompatible. IR spectra showed no interaction between APM and ME components. Optimized AME and AMME formulations were found to be stable for the period of 6 months. Looking at the results of physicochemical properties and ex vivo studies, it can be concluded that formulated AMME can deliver the APM directly to the brain which has potential of increasing the bioavailability of APM which may alleviate side effects by decreasing the dose and frequency of administration. © 2017, The Korean Society of Pharmaceutical Sciences and Technology.