108 Comparative in vitro characterisation of colistimethate sodium 1 MIU/3 ml versus 2 MIU/4 ml in an eFlow® rapid Nebuliser

Abstract

The advantages of nebulised colistimethate sodium (CMS) in the treatment of cystic fibrosis (CF) have been shown in a number of clinical trials. Its widespread use over four decades has proven its safety and efficacy. The treatment of lung infections by inhalation of CMS offers the possibility to achieve high antibiotic drug concentrations at the airway surface. A product offering the advantage of two CMS dose strengths, 1MIU ColiFin® in 3ml 0.9% saline and 2MIU ColiFin® in 4ml 0.9% saline, was aerosol characterised in-vitro after nebulisation with an eFlow®rapid electronic nebuliser. The delivered dose was assessed by breath simulation experiments. NGI experiments were conducted to measure the size distribution of the aerosol. The respirable dose (RD) representing the amount of drug in droplets <5mm was calculated. In-vitro results for the eFlow®rapid loaded with 1 MIU of CMS dissolved in 3ml saline indicated a delivered dose of 27.0mg after 3.8 min of nebulisation. The observed MMAD was 4.1mm and the calculated respirable dose was 18.0mg CMS in droplets <5mm. For 2 MIU of CMS dissolved in 4ml saline a delivered dose of 57.8mg was obtained with a nebulisation time of 6.2min. The respirable dose was 40mg (droplets <5mm). Charging the eFlow®rapid with 2 MIU CMS/4ml results in a twofold higher respirable dose taking only about 2.5 more minutes for inhalation compared to the lower dose strength (1MIU/3ml). Patients in need of high dose CMS inhalation may prefer ColiFin® 2 MIU nebulised with the eFlow®rapid due to its short nebulisation time coupled with a reliable twofold respirable dose.