Inhaled mucoactive particles with tailored architecture for enhanced aerodynamicity, stability and efficacy.

Abstract

In respiratory and genetic disorders such as asthma, chronic obstructive pulmonary disease (COPD), chronic bronchitis and cystic fibrosis (CF), the lungs produce excess mucus, resulting in a thickened mass, which clogs up the airways and reduces airflow. Consequently, breathing becomes more difficult. Medications that break down the structure of mucus will be especially useful in managing the early symptoms of these diseases and preventing their progression into the more severe forms. This work therefore seeks to develop an inhaled mucoactive dry powder formulation that is efficacious on multiple fronts. As an innovative step, sodium chloride was used to tailor the surface architecture of ambroxol hydrochloride particles, such that the resulting angular features on the surfaces contributed to the creation of corrugated particles with enhanced aerodynamicity. The optimized spray-dried powder particles were of respirable-size (d50 of 2.85 ± 0.15 μm) and moderately corrugated. When the crystalline powder was dispersed via an Aerolizer® inhaler at 60 L/min, it gave a fine particle fraction (FPF) of ~31%, which was a ten-fold improvement over the unmodified species (i.e. ambroxol hydrochloride alone). Tests on artificial sputum medium (ASM) showed that the optimized formulation was potentially useful in liquefying the mucus, which favorably pointed towards the effectiveness of the formulation. In addition, the formulation was also stable to moisture ingress (up to ~60% RH) and had good flowability. Hence, the advent of angular adjuvant sodium chloride particles in a mucoactive formulation conferred a three-fold benefit to the product: (1) Improved aerodynamicity and flowability, (2) Enhanced moisture stability and (3) Synergistic mucolytic properties.