Novel spray-dried lactose-leucine tailored to enhance the aerosolization performance in DPI formulations


Spray-drying allows to modify the physicochemical/mechanical properties of particles along with their morphology. In the present study, L-leucine with varying concentrations (0.1, 0.5, 1, 5, and 10% w/v) were incorporated into lactose monohydrate solution for spray-drying to enhance the aerosolization performance of dry powder inhalers containing spray-dried lactose-leucine and salbutamol sulfate. The prepared spray-dried lactose-leucine carriers were analyzed using laser diffraction (particle size), differential scanning calorimetry (thermal behavior), scanning electron microscopy (morphology), powder X-ray diffraction (crystallinity), Fourier transform infrared spectroscopy (interaction at molecular level), and in vitro aerosolization performance (deposition). The results showed that the efficacy of salbutamol sulfate’s aerosolization performance was, in part, due to the introduction of L-leucine in the carrier, prior to being spray-dried, accounting for an increase in the fine particle fraction (FPF) of salbutamol sulfate from spray-dried lactose-leucine (0.5% leucine) in comparison to all other carriers. It was shown that all of the spray-dried carriers were spherical in their morphology with some agglomerates and contained a mixture of amorphous, α-lactose, and β-lactose. It was also interesting to note that spray-dried lactose-leucine particles were agglomerated during the spray-drying process to make coarse particles (volume mean diameter of 79 to 87 μm) suitable as a carrier in DPI formulations.



L-Leucine’s addition allowed for the emergence of a more effective aerosolization performance as it assisted in the alter- ing of lactose monohydrate’s physicochemical properties in such a way as to provide a two-fold increase in the fine particle fraction that equates to an increase in salbutamol sulfate’s concentration in the lower respiratory tract. In addition, through this study, it has been proven that L-leucine improves the stability of amorphous spray-dried lactose as was evident from DSC traces while simultaneously providing a lubrication effect for the formulations that were studied.

Agglomerated novel spray-dried lactose-leucine tailored as a carrier to enhance the aerosolization performance of salbutamol sulfate from DPI formulations
Molina, C., Kaialy, W., Chen, Q. et al. Drug Deliv. and Transl. Res. (2017).
Agglomerated novel spray-dried lactose-l
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