Investigation of L-leucine in reducing the moisture-induced deterioration of spray-dried salbutamol sulfate power for inhalation

Liang Li; Sharon Shui Yee Leung; Thomas Gengenbach; Jiaqi Yu; Ge Fiona Gao; Patricia Tang; Qi Tony Zhou; Hak-Kim Chan

doi:10.1016/j.ijpharm.2017.07.033

Investigation of L-leucine in reducing the moisture-induced deterioration of spray-dried salbutamol sulfate power for inhalation

Int J Pharm. 2017 Sep 15;530(1-2):30-39. doi: 10.1016/j.ijpharm.2017.07.033. Epub 2017 Jul 11.

Authors

Liang Li¹, Sharon Shui Yee Leung², Thomas Gengenbach³, Jiaqi Yu², Ge Fiona Gao⁴, Patricia Tang², Qi Tony Zhou⁵, Hak-Kim Chan⁶

Affiliations

¹ Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales 2006, Australia; School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
² Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales 2006, Australia.
³ CSIRO Manufacturing, Bayview Avenue, Clayton, Victoria 3168, Australia.
⁴ Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales 2006, Australia; Institute of Pharmaceutical Technology, Goethe University, Frankfurt 60438, Germany.
⁵ Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, IN 47907-2091, USA.
⁶ Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales 2006, Australia. Electronic address: kim.chan@sydney.edu.au.

PMID: 28709940
DOI: 10.1016/j.ijpharm.2017.07.033

Abstract

The aim of this study was to investigate the ability of L-leucine (LL) in preventing moisture-induced deterioration in the in vitro aerosolization performance of spray-dried (SD) salbutamol sulfate (SS). Increasing mass fraction of LL (5-80%) were co-spray dried with SS, and the physicochemical properties of the powders were characterized by laser diffraction, X-ray powder diffraction (XRD) and dynamic vapour sorption (DVS). Furthermore, the surface morphology and chemistry of fine particles was analyzed by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The in vitro aerosolization performance of powders stored at different relative humidity (RH) was evaluated by a next generation impactor (NGI). The SD SS powders were moderately hygroscopic and amorphous, of which the uptake of moisture upon storage caused a drop in the aerosolization performance. The results showed that 40% (w/w) LL was sufficient to eliminate the effect of moisture on the aerosolization performance at 60% RH. The formulation containing 40% (w/w) LL also maximized the aerosolization performance of SD SS powders (stored in desiccator) with the emitted fraction being 90.0±1.8%, and the fine particle fraction based on the recovered dose (FPF_recovered) and emitted dose (FPF_emitted) being 78.0±3.7% and 86.6±2.9%, respectively. The underlying mechanisms were that the crystalline LL increased the degree of particle surface corrugation, and reduced particle fusion and cohesiveness to facilitate dispersion. However, there is still a great challenge to prevent the moisture-induced deterioration in the aerosolization performance at 75% RH due to the recrystallization of SD SS. In conclusion, LL is a potential excipient for reducing moisture-induced deterioration in the aerosolization performance of SD amorphous powders, but still has drawbacks in preventing the recrystallization-induced deterioration.

Keywords: Dry powder inhalers; L-leucine; Moisture protection; Recrystallization; Salbutamol sulfate; Spray drying.

MeSH terms

Administration, Inhalation*
Aerosols
Albuterol / administration & dosage*
Chemistry, Pharmaceutical
Leucine / chemistry*
Particle Size
Powders*

Substances

Aerosols
Powders
Leucine
Albuterol