Abstract

ARIPIPRAZOLE NANOSPONGE: NASAL IN-SITU GEL FORMULATION FOR NOSE TO BRAIN DELIVERY

Rana Zainuddin Ahmed*, Sonal Shaharwale, Jaiprakash Sangshetti and Shaikh Wasim Abdul Gani

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Abstract

Aripiprazole offers treatment for schizophrenia but the drug undergoes significant degradation in GI tract leading to poor bioavailablity. The aim of present study is to formulate in-situ nasal gel for nose to brain delivery of Aripiprazole loaded nanosponge (ARP-NS) to achieve better treatment outcomes. Method: Nanosponges (NS) offer the advantage of enhanced dissolution, permeation and drug stability. NS were prepared using β-CD and diphenyl carbonate; parallel reaction synthesizer at temperature 85°C, 1000 rpm. The formulation was optimized for Carbopol 940 and HPMC K100 concentration using 32 factorial designs. The ARP-NS was characterized by FTIR, DSC, XRPD, zeta size and SEM. The formulations were evaluated for parameters such as pH, drug content, viscosity, drug release, mucoadhesion, ex-vivo permeation and stability studies. Results: The PyMOL Molecular Graphics software was used to model β –CD NS and entrapment of Aripiprazole in the cavity, which along with other characterization techniques confirmed drug entrapment. Drug release from formulation and plain drug was found to be 93.85 ± 0.43% and 41.92 ± 0.36% respectively in 6 h. Treatment outcome was better from in-situ gel formulation compared to oral ARP solution on performing locomotor studies on psychosis induced rats. Pharmacokinetic evaluation was performed on Sprauge dawley male rats. Cmax, Tmax & AUC of ARP-NS (in brain) was found to be 4929 ± 21.56 ng/mL, 3 h and 930.35 ± 24.5 ng.h/mL. Conclusion: This study showed that Aripiprazole could be delivered effectively to the brain using nanosponge incorporated in in-situ gel which produced sustained drug release.

Keywords: Nanosponges, nose to brain delivery, Schizophrenia, Pharmacokinetics, locomotor activity.