Abstract
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.
Highlights
Pulmonary drug delivery to treat lung infections is an important area of research [1,2]
No change in fine particle fraction (FPF) or respirable fraction-3μm (RF3μm) was observed for the KM formulation, methionine transformed into its crystalline counterpart (Figure S9) by 24 h
Co-amorphous formulations of kanamycin can be produced by co-spray drying with valine, methionine, phenylalanine, and tryptophan
Summary
Pulmonary drug delivery to treat lung infections is an important area of research [1,2]. Amino acid-based co-amorphous systems have recently been introduced as a potential strategy to improve the stability of amorphous material [25,26] This technique is being explored to improve aerosol performance of inhalable spray-dried particles. The aerosolization of budesonide-arginine co-amorphous spray-dried powder was higher than budesonide alone [22] These particles were not prepared using the same experimental conditions (solvent system and spray dryer operating parameters). Four different amino acids (valine, methionine, phenylalanine, and tryptophan) were chosen for the preparation of potential inhalable co-amorphous particles using spray drying (Figure 1). Kanamycin sulfate was spray dried with different amino acids (valine, methionine, phenylalanine, and Ktraynpatompyhcainn) asut lafa1t:e1 mwoalsar srpartaioy. Specific spectral range (900–1000 cm−1) was used for the band analysis, and fitted peak positions were determined using the peak find function (default settings) in the SpectraGryph 1.2.14. software [37]
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