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 lactoseleucine 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.

Co-spraying of carriers (mannitol-lactose) as a method to improve aerosolization performance of salbutamol sulfate dry powder inhaler

“…Spray drying was conducted using the Mini Spray Dryer B-290 from Buchi (Flawil, Switzerland) equipped with a dehumidifier (Dehumidifier B-296), an inert loop (Inert Loop B-295), and an outlet filter in a closed system with the use of nitrogen (N 2 ) gas. Parameters associated with the procedure are outlined elsewhere [7]. To summarize, the inlet temperature was 220°C, aspirator set at 100%, pump rate set at 5%, and the flow rate set at 22%.…”

“…Carriers and leucine were dissolved in deionized (DI) water while heating the solution to 75°C under stirring at 120 rpm. The final solutions were spray-dried under the conditions mentioned elsewhere [7].…”

“…Perkin Elmer's (Shelton, Connecticut, USA) Differential Scanning Calorimetry (DSC) 4000 equipped with a Standard Single-Furnace was used to perform thermodynamic analysis; viewing and analyzing the data was completed with the accompanied Pyris Series software. Using a modified protocol outlined by Molina et al [7], the scanning rate was decreased to 5°C/min as such rate is known to provide a more thorough thermal analysis [20,25]. Nonetheless, each of the samples was accurately weighed, where the mass ranged from 4 to 5 mg per sample, on aluminum pans and sealed with an aluminum cap; calibration was completed through the use of indium and zinc prior to any analysis.…”

“…It has been shown that spray drying can be used to manipulate the properties of a carrier to achieve a better aerosolization performance through aggregated spray-dried lactose particles [7]. Nevertheless, the array by which spray drying becomes applicable coincides with its advantages over other traditional methods such as ball milling or micronization.…”

“…Their unique chemical profiles allow for them to be labeled as generally recognized as safe (GRAS) by the US Food and Drug Administration (US FDA) and by the European Pharmaceutical Union (EPU). It has been shown that the incorporation of leucine in spray-dried lactose [7] or mannitol [22] could improve the aerosolization performance of salbutamol sulfate, and this was the case when binary mixtures of mannitol-lactose were used [23,24]. However, none of the previous studies employed spray drying technology to spray dry binary mixtures of sugars containing leucine simultaneously (ternary mixtures overall).…”