Effects of Humidity and Excipients on Aerosol Performance and Electrostatic Charge of Spray-dried Powders for Inhalation

Abstract

Relative humidity (RH) or moisture content in the environment is an imperative factor that needs to be considered when it comes to the stability-related issues of inhaled dry powder formulations. Spray drying is one primary used technique for producing inhalable powders. However, it is a process that often leaves the powders amorphous and physically unstable. The existence of amorphous materials in pharmaceutical powders can affect the processing, storage, and delivery properties. If stored improperly, amorphous powders would absorb relatively large amounts of water from the surrounding, impacting significantly the long-term stability and performance of the powder formulations. In addition, RH could also impact aerosol deposition by affecting the electrostatic charge of particles, because electrostatic charge is one of the five mechanisms that governs aerosol deposition in the lung. In this thesis, we investigated the role of RH in pharmaceutical dry powder aerosols, with the following specific objectives: 1. To investigate the protective effect of hydrophobic excipients (amino acids and sodium stearate) against moisture-induced deterioration of the aerosolization performance in highly hygroscopic spray-dried powders. 2. To investigate the effects of storage humidity and hydrophobic excipients on electrostatic charge profiles of spray-dried powders for inhalation, using a novel Bipolar Charge Analyzer (BOLARTM, Dekati®, Finland).