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

  • Santosh Ashok Kumbhar
    School of Pharmaceutical Sciences, Jaipur National University, Jaipur 302 017, Rajasthan, India

    Department of Pharmaceutics, STES's Sinhgad Institute of Pharmacy (Affiliated to Savitribai Phule Pune University), Narhe, Pune 411 041, Maharashtra, India
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  • Chandrakant R. Kokare
    Department of Pharmaceutics, STES's Sinhgad Institute of Pharmacy (Affiliated to Savitribai Phule Pune University), Narhe, Pune 411 041, Maharashtra, India
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  • Birendra Shrivastava
    Corresponding author.
    School of Pharmaceutical Sciences, Jaipur National University, Jaipur 302 017, Rajasthan, India
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  • Bapi Gorain
    School of Pharmacy, Faculty of Health and Medical Science, Taylor's University, Subang Jaya, Selangor, Malaysia

    Centre for Drug Delivery and Molecular Pharmacology, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Selangor, Malaysia
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  • Hira Choudhury
    Corresponding author. School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur 47000, Malaysia.
    Department of Pharmaceutical Technology, School of Pharmacy, International Medical University, Bukit Jalil, 57000 Kuala Lumpur, Malaysia

    Centre for Bioactive Molecules and Drug Delivery, Institute for Research, Development and Innovation, International Medical University, Bukit jalil, 57000 Kuala Lumpur, Malaysia
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Published:January 26, 2021DOI:


      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 in vitro release profile of the formulation was in agreement to enhanced ex vivo permeation through sheep mucous membranes with a maximum rate of permeation co-efficient (62.87  cm h−1 × 103) and flux (31.43  μg cm−2.h−1). The pharmacokinetic profile following single-dose administration showed the maximum concentration of drug in the brain (Cmax) of 15.19 ± 2.51  μg mL−1 and Tmax of 1 h in animals with ARP-MNE as compared to 10.57 ± 1.88  μg mL−1 and 1 h, and 2.52 ± 0.38  μg mL−1 and 3 h 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 ex vivo 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.


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