Investigation of moisture scavengers in pressurized metered-dose inhalers

Moisture ingress into pressurized metered-dose inhalers (pMDIs) and its inf luence on the formulation stability of pMDIs has been reported. This resear ch work was undertaken to investigate a prototype moisture scavenger system to minimize the water level in pMDIs in order to control drug crystal grow th, degradation,and erratic drug delivery performance. Uncoated or hydroxyp ropyl methylcellulose (HPMC) coated silica gel beads (SGB), aluminum desicc ant beads (ADB), and molecular sieve beads (MSB) were incorporated into con trol and water spiked pMDIs containing HFA 134a or HFA 227. The water level s in pMDI were determined by Karl-Fischer titration. The water scavenge eff iciency of different desiccants was compared. Generation of desiccant parti cles or HPMD in the emitted dose was evaluated by examining the existence a nd concentration of desiccant particles and HPMC in the aerosol cloud using energy dispersive spectroscopy (EDS), atomic absorption spectrophotometry, and gel permeation chromatography (GPC). The water level in the water-spik ed pMDIs was significantly decreased compared to the control pMDIs when des iccants were incorporated into the pMDIs. The moisture scavenging ability o f uncoated and HPMC coated SGB, ADB, and MSB were similar. Pre-washing desi ccant beads using HFA 134a or HFA 227 prior to incorporation into pMDIs pre vented the generation of silica particles in the aerosol cloud emitted from pMDIs containing SGB. HPMC coating of ADB adn MSB also effectively prevent ed the generation of desiccant particles in the aerosols emitted from these desiccant-containing pMDIs. The concentration of HPMC in the aerosols emit ted from pMDIs containing HPMC coated desiccants was extremely low. Pre-was hed SGB and HPMC coated ADB and MSB were effective moisture scavengers in t he pMDI systems investigated. The results of this investigation indicated t hat incorporation of these prototype desiccant systems into pMDIs may minim ize the undesired consequences caused by moisture ingress into pMDI caniste rs.