Effect of the Moisture Content in Aerosol on the Spray Performance of Stmerin<sup>®</sup> D Hydrofluoroalkane Preparations (2)

Abstract

The spray performance of the new Stmerin® D pressurized metered dose inhalers (MDIs), prescribed for asthma treatment, was previously reported to be sensitive to moisture content in the canister. In this formulation, active ingredients were suspended in hydrofluoroalkanes (HFA-134a and HFA-227). Here, we report on the critical moisture content of a new MDI formulation using HFA-227. We prepared MDIs with different moisture contents (107-331 ppm) and investigated the effect of moisture content on the fine particle dose (FPD). When the moisture content exceeded 280 ppm, FPD was reduced by 20%. The moisture content can be kept below this level by controlling moisture ingress with selected sealing gasket materials and by controlling the manufacturing conditions. The long-term stability and moisture penetration rate at 25°C and 60% relative humidity (RH) of the new HFA-227 formulation were tested over 36 months. Moisture content increased to approximately 210 ppm after 24 months and 230 ppm after 36 months storage; the drug content did not change over 24 months; FPD was slightly reduced by 24 months but still complied with the product specification. These results demonstrate that the critical moisture content of the Stmerin® D HFA-227 MDI formulation to meet required spray performance is between 280 and 330 ppm, and this formulation (at <210 ppm moisture level) is stable over 24 months.