Design of inhalation dry powder of pranlukast hydrate to improve dispersibility by the surface modification with light anhydrous silicic acid (AEROSIL 200)

Abstract

A new particle design method was proposed for dry powder inhalation of hydrophobic cohesive drug particles (pranlukast hydrate, D 50=2.1 μm) by the surface modification with hydrophilic colloidal silica (AEROSIL, D 50=16 nm). The surface of drug particle was modified by compounding AEROSIL (2–10%) under shear with a manually operating mortar (PM method) or a high-speed elliptical-rotor-type mixer (Theta-Composer ®, TC method). The surface modifications were also conducted by lyophilizing (FD method) or spray drying (SD method) the aqueous dispersions of the drug and AEROSIL. The surface modified particles were aerosolized through a Spinhaler ® and their inhalation behaviors were evaluated by a twin impinger in vitro. The inhalation behaviors were evaluated by the coefficient of inhalation efficiency (EI) defined as the geometric mean of the drug % emitted from the device and delivered % in respirable fraction of the twin impinger. The EI of modified particles with TC, FD and SD methods were dramatically increased up to 66.9, 52.7 and 47.7%, respectively, with increasing AEROSIL content compared with that of (22.4%) original powder. The surface modification to hydrophilic with AEROSIL reduced the cohesive force between the drug particles, owing to the decrease in van der Waals and electrostatic forces, improving the dispersibilities of emitted particles from the Spinhaler ®.