The crucial role of leucine concentration on spray dried mannitol-leucine as a single carrier to enhance the aerosolization performance of Albuterol sulfate

Abstract

Generally, DPI formulations show low fine particle fraction (FPF) due to poor detachment of drug particles from carrier during inhalation. l-Leucine, with varying concentrations (ranging from 0 to 10% w/w), were introduced into a 60%w/v mannitol solution where the solutions were then spray dried to achieve a new processed carrier. The spray dried samples were blended with Albuterol sulfate to determine the efficacy of their aerosolization performance. Analyzing each formulation was completed via the implementation of numerous analytical techniques such as particle size distribution analysis via laser diffraction, differential scanning calorimetry (DSC), scanning electron microscope (SEM), powder X-Ray diffraction (PXRD), Fourier transform infrared (FT-IR) spectroscopy, and an in vitro deposition study. It was shown the concentration of leucine in spray dried is really crucial to achieve the highest FPF possible. The highest FPF was obtained for the samples containing 10% w/w leucine which was 52.96 ± 5.21%. It was interesting to note that the presence of leucine produced different polymorphic forms for mannitol. Moreover, through this study, the authors were able to conclude that mannitol can serve as an alternative carrier in DPI formulations containing Albuterol sulfate tailored for lactose intolerant patients.