Inhaled hyaluronic acid microparticles extended pulmonary retention and suppressed systemic exposure of a short-acting bronchodilator

The aim of this study was to investigate the feasibility of using hyaluronic acid (HA), a biomucoadhesive carbohydrate polymer to prolong the pulmonary retention and reduce the systemic exposure of inhaled medicine. Salbutamol sulphate (SAS), a model bronchodilator, was co-spray dried with HA into inhalable microparticles, which were subsequently characterized as spherical shape with wrinkled surface. The fine particle fraction of the microparticles tested by using the Next Generation Impactor was over 30% without the aid of any carrier, and the in vitro release of SAS lasted for 20 h. Compared to spray-dried plain SAS powders, the SAS-loaded HA microparticles possessed enhanced biomucoadhesive property in vitro and had much longer pulmonary retention and reduced systemic exposure in vivo. By incorporation, the pulmonary retention time of SAS was prolonged from 2 h to 8 h while the maximum concentration in plasma was reduced significantly from 2267.7 ng/mL to 566.38 ng/mL. These results suggested that inhaled HA microparticles could be a promising formulation strategy to enhance the therapeutic efficacy of inhaled medicines. (C) 2017 Elsevier Ltd. All rights reserved.