Design of an Oral Tablet Containing Furosemide Nanoparticles with Elevated Bioavailability

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  • Nagai Noriaki
    Faculty of Pharmacy, Kindai University
  • Ogata Fumihiko
    Faculty of Pharmacy, Kindai University
  • Kadowaki Reita
    Faculty of Pharmacy, Kindai University
  • Deguchi Saori
    Faculty of Pharmacy, Kindai University
  • Otake Hiroko
    Faculty of Pharmacy, Kindai University
  • Nakazawa Yosuke
    Faculty of Pharmacy, Keio University
  • Misra Manju
    Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research Graduate School of Pharmacy, Gujarat Technological University, Gandhinagar Campus Nr. Government Polytechnic K-6 Circle, E-4 Electronic Estate G.I.D.C
  • Kawasaki Naohito
    Faculty of Pharmacy, Kindai University

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<p>The solubility and permeability of the Biopharmaceutics Classification System (BCS) class IV drugs, such as furosemide (FUR), are low. Thus, the oral bioavailability of these drugs needs to be augmented. Here, we aimed to design orally disintegrating tablets containing FUR nanoparticles to improve bioavailability after oral administration. The FUR nanoparticles were generated by bead-milling in water containing 0.5% methylcellulose and 0.5% 2-hydroxypropyl-β-cyclodextrin (w/w%). Particle size was approximately 47–350 nm (mean particle size, 188 nm). An orally disintegrating tablet (FUR-NP tablet) comprising FUR nanoparticles (1%) was successfully produced by employing suspensions outlined above that incorporated additives (4% D-mannitol, 0.4% polyvinylpyrrolidone, and 16% gum Arabic, w/w%), followed by freeze-drying. The FUR-NP tablet disaggregated after only 5 s in water, liberating nano-sized FUR particles (172 nm). Experiments using rats showed the absorption of the FUR-NP tablet was significantly improved by comparison with a FUR tablet containing microparticles. In summary, the orally disintegrating tablet containing FUR nanoparticles markedly enhanced the bioavailability of FUR. We anticipate this formulation will also improve the bioavailability of other BCS class IV drugs.</p>

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