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.

OriginalsprogEngelsk
Artikelnummer104961
TidsskriftEuropean Journal of Pharmaceutical Sciences
Vol/bind136
ISSN0928-0987
DOI
StatusUdgivet - 2019

ID: 241099472