Agglomerated novel spray-dried lactose-leucine tailored as a carrier to enhance the aerosolization performance of salbutamol sulfate from DPI formulations

Abstract

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.

Keywords: Agglomeration; Dry powder inhaler; Leucine; Salbutamol sulfate; Spray-drying.

Fig. 1

Particle size distribution (PSD) diagrams of each carrier when using the a RODOS dry system and when using the b CUVETTE wet system; the carriers used were spray-dried lactose monohydrate containing 0, 0.1, 0.5, 1, 5, and 10% _L-leucine

Fig. 2

SEM images of a spray-dried lactose monohydrate, spray-dried lactose containing-leucine where leucine concentrations were b 0.1%, c 0.5%, d 1%, e 5%, and f 10%

Fig. 3

DSC thermal peaks of _L-leucine, commercial lactose monohydrate, spray-dried lactose monohydrate-leucine where the concentration of leucine were 0, 0.1, 0.5, 1, 5, and 10% w/v (where an exothermic peak would point up and an endothermic peak would point down)

Fig. 4

X-ray diffraction patterns of spray-dried lactose monohydrate and spray-dried lactose monohydrate-leucine where the concentrations of leucine were 0.1, 0.5, 1, 5, and 10%

Fig. 5

FT-IR spectra of pure _L-leucine, spray-dried lactose monohydrate, and spray-dried lactose monohydrate-leucine where the concentrations of leucine were 0.1, 0.5, 1, 5, and 10% highlighting the areas that are eliminated or broadened as the concentration of _L-leucine increases while also showing where the amorphous, α-lactose, and β-lactose peaks are to be found

Fig. 6

Aerosolization performance of each of the formulations (spray-dried lactose monohydrate and spray-dried lactose monohydrate-leucine where the concentrations of leucine were 0.1, 0.5, 1, 5, and 10% highlighting the amount of SS recovered (percent recovered)