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Development and Optimization of Asenapine Sublingual Film Using QbD Approach

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Abstract

Asenapine, an atypical antipsychotic agent, has been approved for the acute and maintenance treatment of schizophrenia and manic episodes of bipolar disorder. However, the extensive hepatic metabolism limits its oral bioavailability. Therefore, the objective of the current investigation was to develop sublingual film containing asenapine to enhance the therapeutic efficacy. Sublingual films containing asenapine were fabricated using polyethylene oxide and hydroxypropyl methylcellulose by solvent casting method. Design of experiment was used as a statistical tool to optimize the proportion of the film-forming polymers in order to establish the critical quality attributes of the drug formulation. The process was studied in detail by assessing risk of each step as well as parameters and material attributes to reduce the risk to a minimum. A control strategy was defined to ensure manufacture of films according to the target product profile by evaluation of intermediate quality attributes at the end of each process step. Results of optimized formulations showed rapid disintegration, adequate folding endurance, good percentage elongation, tensile strength, and viscosity. Besides, the results from the in vitro dissolution/ex vivo permeation studies showed rapid dissolution (100% in 6 min) and higher asenapine permeation (~ 80% in 90 min) through the sublingual epithelium. In vivo study indicates greater asenapine absorption (31.18 ± 5.01% of administered dose) within 5 min and was comparable with marketed formulation. In summary, the designing plan to develop asenapine formulation was successfully achieved with desired characteristics of the delivery tool for sublingual administration.

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Acknowledgements

The authors acknowledge Sun Pharmaceuticals Industries Ltd, Vadodara, India, for providing drug and polymers.

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Authors and Affiliations

  1. Department of Pharmaceutics, Institute of Pharmacy, Nirma University, Ahmedabad, 382481, Gujarat, India

    Rahil Dalal, Jigar Shah & Tejal A. Mehta

  2. School of Pharmacy, Faculty of Health and Medical Sciences, Taylor’s University, 47500, Subang Jaya, Selangor, Malaysia

    Bapi Gorain

  3. Centre for Drug Delivery and Molecular Pharmacology, Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya, 47500, Selangor, Malaysia

    Bapi Gorain

  4. School of Pharmacy, International Medical University, Bukit Jalil, 57000, Kuala Lumpur, Malaysia

    Hira Choudhury

  5. Department of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University, 4184, Ajman, United Arab Emirates

    Shery Jacob

  6. Department of Pharmaceutics, Arihant School of Pharmacy & BRI, AdalajGandhinagar, 382421, Gujarat, India

    Hiral Shah

  7. Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, 31982, Al-Ahsa, Saudi Arabia

    Anroop B. Nair

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  1. Rahil Dalal
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Contributions

Conceptualization: Rahil Dalal, Jigar Shah, Bapi Gorain, Shery Jacob, and Anroop B. Nair; data curation: Rahil Dalal, Jigar Shah, Bapi Gorain, Hira Choudhury, and Shery Jacob; formal analysis: Rahil Dalal, Jigar Shah, Hira Choudhury, Shery Jacob, Tejal A. Mehta, Hiral Shah, and Anroop B. Nair; methodology: Rahil Dalal, Jigar Shah, Bapi Gorain, Hira Choudhury, Shery Jacob, Tejal A. Mehta, Hiral Shah, and Anroop B. Nair; writing—original draft preparation: Rahil Dalal, Tejal A. Mehta, and Hiral Shah; writing—review and editing: Jigar Shah, Bapi Gorain, Hira Choudhury, Shery Jacob, and Anroop B. Nair. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Jigar Shah.

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Dalal, R., Shah, J., Gorain, B. et al. Development and Optimization of Asenapine Sublingual Film Using QbD Approach. AAPS PharmSciTech 22, 244 (2021). https://doi.org/10.1208/s12249-021-02132-5

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