Co-amorphization of Kanamycin with amino acids improves aerosolization

Bishal Raj Adhikari, Karlis Bērziņš, Sara J. Fraser-Miller, Keith C. Gordon, Shyamal C. Das

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)
14 Downloads (Pure)


Different formulation techniques have been investigated to prepare highly aerosolizable dry powders to deliver a high dose of antibiotics to the lung for treating local infections. In this study, we investigated the influence of the co-amorphization of a model drug, kanamycin, with selected amino acids (valine, methionine, phenylalanine, and tryptophan) by co-spray drying on its aerosolization. The co-amorphicity was confirmed by thermal technique. The physical stability was monitored using low-frequency Raman spectroscopy coupled with principal component analysis. Except for the kanamycin-valine formulation, all the formulations offered improved fine particle fraction (FPF) with the highest FPF of 84% achieved for the kanamycin-methionine formulation. All the co-amorphous formulations were physically stable for 28 days at low relative humidity (25 C/<15% RH) and exhibited stable aerosolization. At higher RH (53%), even though methionine transformed into its crystalline counterpart, the kanamycin-methionine formulation offered the best aerosolization stability without any decrease in FPF. While further studies are warranted to reveal the underlying mechanism, this study reports that the co-amorphization of kanamycin with amino acids, especially with methionine, has the potential to be developed as a high dose kanamycin dry powder formulation.

Original languageEnglish
Article number715
Pages (from-to)1-19
Number of pages19
Issue number8
Publication statusPublished - Aug 2020
Externally publishedYes


  • Aerosolization
  • Amino acids
  • Co-amorphous
  • Dry powder
  • Kanamycin
  • Low-frequency Raman spectroscopy
  • Principal component analysis
  • Stability


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