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Formulation of Ketotifen Fumarate Fast-Melt Granulation Sublingual Tablet

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Abstract

The purpose of this study was to prepare sublingual tablets, containing the antiasthmatic drug ketotifen fumarate which suffers an extensive first-pass effect, using the fast-melt granulation technique. The powder mixtures containing the drug were agglomerated using a blend of polyethylene glycol 400 and 6000 as meltable hydrophilic binders. Granular mannitol or granular mannitol/sucrose mixture were used as fillers. A mechanical mixer was used to prepare the granules at 40°C. The method involved no water or organic solvents, which are used in conventional granulation, and hence no drying step was included, which saved time. Twelve formulations were prepared and characterized using official and non official tests. Three formulations showed the best results and were subjected to an ex vivo permeation study using excised chicken cheek pouches. The formulation F4I possessed the highest permeation coefficient due to the presence of the permeation enhancer (polyethylene glycol) in an amount which allowed maximum drug permeation, and was subjected to a pharmacokinetic study using rabbits as an animal model. The bioavailability of F4I was significantly higher than that of a commercially available dosage form (Zaditen® solution-Novartis Pharma-Egypt) (p > 0.05). Thus, fast-melt granulation allowed for rapid tablet disintegration and an enhanced permeation of the drug through the sublingual mucosa, resulting in increased bioavailabililty.

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Acknowledgments

We are so much obliged to the agents of Roquette, France and JRS, Germany for supplying us with the necessary chemicals as gifts to participate in the field of research.

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Authors and Affiliations

  1. Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt

    Saadia A. Tayel & Iman I. Soliman

  2. Faculty of Pharmacy, Cairo University, Kasr El Eini Street, Cairo, Egypt

    Dina Louis

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  1. Saadia A. Tayel
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  2. Iman I. Soliman
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Correspondence to Dina Louis.

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Tayel, S.A., Soliman, I.I. & Louis, D. Formulation of Ketotifen Fumarate Fast-Melt Granulation Sublingual Tablet. AAPS PharmSciTech 11, 679–685 (2010). https://doi.org/10.1208/s12249-010-9425-9

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