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Thermoreversible Carbamazepine In Situ Gel for Intranasal Delivery: Development and In Vitro, Ex Vivo Evaluation

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Abstract

Over the past decade, intranasal (IN) delivery has been gaining attention as an alternative approach to conventional drug delivery routes targeting the brain. Carbamazepine (CBZ) is available as an orally ingestible formulation. The present study aims to develop a thermoreversible in situ gelling system for delivering CBZ via IN route. A cold method of synthesis has been used to tailor and optimize the thermoreversible gel composition, using poloxamer 407 (P407) (15–20% w/v) and iota carrageenan (ɩ-Cg) (0.15–0.25% w/v). The developed in situ gel showed gelation temperatures (28–33°C), pH (4.5–6.5), rheological properties (pseudoplastic, shear thinning), and mucoadhesive strength (1755.78–2495.05 dyne/cm2). The in vitro release study has shown sustained release behavior (24 h) for gel, containing significant retardation of CBZ release. The release kinetics fit to the Korsmeyer–Peppas model, suggesting the non-Fickian diffusion type controlled release behavior. Ex vivo permeation through goat nasal mucosa showed sustained release from the gel containing 18% P407 with the highest cumulative drug permeated (243.94 µg/cm2) and a permeation flux of 10.16 µg/cm2/h. After treatment with CBZ in situ gel, the barrier function of nasal mucosa remained unaffected. Permeation through goat nasal mucosa using in situ gel has demonstrated a harmless nasal delivery, which can provide a new dimension to deliver CBZ directly to the brain bypassing the blood–brain barrier.

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Funding

The research was conducted under the Fundamental Research Grant Scheme (FRGS 17-006-0572), sponsored by the Ministry of Higher Education, Malaysia.

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Authors and Affiliations

  1. AIMST University, Bukit Air Nasi 3 ½, Jalan Bedong, Semeling, Malaysia

    K. Mohananaidu

  2. Kulliyyah of Pharmacy, International Islamic University Malaysia, 25200, Kuantan, Malaysia

    K. Mohananaidu, Farahidah Mohamed & Samah Hamed Almurisi

  3. Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM’s NMIMS, V.L.Mehta Road, Mumbai, 400055, India

    Bappaditya Chatterjee

  4. Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Syed Mahmood

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  1. K. Mohananaidu
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Contributions

Keithanchali Mohonanaidu (first author): experimental work and data analysis and writing the manuscript.

Bappaditya Chatterjee (corresponding author): conceptualize the idea and framing the research, review and technical editing of the manuscript, helping fabrication of gel, and responding reviewers’ comments.

Farahidah Mohamed (corresponding author): conceptualize the idea and framing the research, helping physicochemical evaluation of gel, mucoadhesion study, and review of the manuscript.

Syed Mahmood (co-author): ex vivo permeation study and its data interpretation.

Samah Hamed (co-author): rheological analysis and its data interpretation.

Corresponding author

Correspondence to Bappaditya Chatterjee.

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Mohananaidu, K., Chatterjee, B., Mohamed, F. et al. Thermoreversible Carbamazepine In Situ Gel for Intranasal Delivery: Development and In Vitro, Ex Vivo Evaluation. AAPS PharmSciTech 23, 288 (2022). https://doi.org/10.1208/s12249-022-02439-x

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