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Formulation and Characterization of Fast-Dissolving Sublingual Film of Iloperidone Using Box–Behnken Design for Enhancement of Oral Bioavailability

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Abstract

Iloperidone is a second-generation antipsychotic drug which is used for the treatment of schizophrenia and has very low aqueous solubility and bioavailability. This drug also undergoes first-pass metabolism. The aim of this work is to formulate fast-dissolving sublingual films of iloperidone to improve its bioavailability. Sublingual films were prepared by solvent casting method. Hydroxypropyl methyl cellulose E5, propylene glycol 400, and transcutol HP were optimized using Box–Behnken three-level statistical design on the basis of disintegration time and folding endurance of films. Iloperidone:hydroxypropyl-β–cyclodextrin kneaded complex was used in films instead of plain drug due to its low solubility. Optimized film was further evaluated for drug content, pH, dissolution studies, ex vivo permeation studies, and pharmacokinetic studies in rats. The optimized film disintegrated within 30 s. The in vitro dissolution of the film showed 80.3 ± 3.4% drug dissolved within first 5 min. In ex vivo permeation studies using sublingual tissue, flux achieved within first 15 min by film was around 117.1 ± 0.35 (mcg/cm2/h) which was ten times more than that of plain drug. This formulation showed excellent uniformity. AUC and Cmax of film were significantly higher (p < 0.001) as compared to plain drug and relative bioavailability of the films was 148% when compared to the plain drug. Thus, this study showed optimized fast-dissolving sublingual film to improve permeation and bioavailability of iloperidone. Fast-dissolving films will be customer-friendly approach for geadiatric schizophrenic patients.

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Acknowledgements

Authors would like to thank Lupin Ltd. for providing iloperidone gift sample and Gattefosse for providing transcutol HP gift sample. We would like to also thank Mr. Ankit Laddha, research scholar, SPPSPTM for helping in pharmacokinetic studies.

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  1. Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM’s NMIMS, Vile Parle (W), Mumbai, Maharashtra, 400056, India

    Vaishali Londhe & Rucha Shirsat

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  1. Vaishali Londhe
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  2. Rucha Shirsat
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Correspondence to Vaishali Londhe.

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Londhe, V., Shirsat, R. Formulation and Characterization of Fast-Dissolving Sublingual Film of Iloperidone Using Box–Behnken Design for Enhancement of Oral Bioavailability. AAPS PharmSciTech 19, 1392–1400 (2018). https://doi.org/10.1208/s12249-018-0954-y

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