Crystalline adduct of moxifloxacin with trans-cinnamic acid to reduce the aqueous solubility and dissolution rate for improved residence time in the lungs

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  • Basanth Babu Eedara
  • Ian G. Tucker
  • Zoran D. Zujovic
  • Rades, Thomas
  • Jason R. Price
  • Shyamal C. Das

A crystalline adduct of the anti-tubercular drug, moxifloxacin and trans-cinnamic acid (1:1 molar ratio (MCA1:1)) was prepared to prolong the residence time of the drug in the lungs by reducing its solubility and dissolution rate. Whether the adduct is a salt or cocrystal has not been unequivocally determined. Equilibrium solubility and intrinsic dissolution rate measurements for the adduct (MCA1:1) in phosphate buffered saline (PBS, pH 7.4) revealed a significant decrease in the solubility of moxifloxacin (from 17.68 ± 0.85 mg mL−1 to 6.10 ± 0.05 mg mL−1) and intrinsic dissolution rate (from 0.47 ± 0.04 mg cm−2 min−1 to 0.14 ± 0.03 mg cm−2 min−1) compared to the supplied moxifloxacin. The aerosolization behaviour of the adduct from an inhaler device, Aerolizer®, using a Next Generation Impactor showed a fine particle fraction of 30.4 ± 1.2%. The dissolution behaviour of the fine particle dose of respirable particles collected was assessed in a small volume of stationary mucus fluid using a custom-made dissolution apparatus. The respirable adduct particles showed a lower dissolution (microscopic observation) and permeation compared to the supplied moxifloxacin. The crystalline adduct MCA1:1 has a lower solubility and dissolution rate than moxifloxacin and could improve the local residence time and therapeutic action of moxifloxacin in the lungs.

Original languageEnglish
Article number104961
JournalEuropean Journal of Pharmaceutical Sciences
Publication statusPublished - 2019

    Research areas

  • Crystalline adduct, Dissolution, Moxifloxacin, Respirable particle, Solubility, Trans-cinnamic acid, Tuberculosis

ID: 241099472