Antipsychotic Potential and Safety Profile of TPGS-Based Mucoadhesive Aripiprazole Nanoemulsion: Development and Optimization for Nose-To-Brain Delivery.

Abstract

Delivering therapeutics to the brain using conventional dosage forms is always a challenge, thus the present study was aimed to formulate mucoadhesive nanoemulsion (MNE) of aripiprazole (ARP) for intranasal delivery to transport the drug directly to the brain. Therefore, a TPGS based ARP-MNE was formulated and optimized using the Box-Behnken statistical design. The improved invitro release profile of the formulation was in agreement to enhanced exvivo permeation through sheep mucous membranes with a maximum rate of permeation co-efficient (62.87cmh-1×103) and flux (31.43μgcm-2.h-1). The pharmacokinetic profile following single-dose administration showed the maximum concentration of drug in the brain (Cmax) of 15.19±2.51μgmL-1 and Tmax of 1h in animals with ARP-MNE as compared to 10.57±1.88μgmL-1 and 1h, and 2.52±0.38μgmL-1 and 3h upon intranasal and intravenous administration of ARP-NE, respectively. Further, higher values of % drug targeting efficiency (96.9%) and % drug targeting potential (89.73%) of ARP-MNE through intranasal administration were investigated. The studies in Wistar rats showed no existence of extrapyramidal symptoms through the catalepsy test and forelimb retraction results. No exvivo ciliotoxicity on nasal mucosa reflects the safety of the components and delivery tool. Further, findings on locomotor activity and hind-limb retraction test in ARP-MNE treated animals established its antipsychotic efficacy. Thus, it can be inferred that the developed ARP-MNE could effectively be explored as brain delivery cargo in the effective treatment of schizophrenia without producing any toxic manifestation.