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Exploring the Relationship between Suspension and Solution Metered Dose Inhaler Formulation Variables and Predicted Lung Deposition

Schroeter JD, Sheth P, Hickey AJ, Asgharian B, Price OT, Holt J, Conti DS, Saluja B.

RDD Asia 2018. Volume , 2018: 111-118.

Abstract:

Metered dose inhaler (MDI) performance metrics such as aerodynamic particle size distribution (APSD) and lung deposition are affected by formulation and device variables. Formulation variables of relevance to two commercially available products: Proventil HFA (albuterol sulfate (AS) suspension) and Qvar (beclomethasone dipropionate (BDP) solution) were evaluated to determine their influence on key in vitro performance attributes measured by cascade impaction. These commercial MDIs were used as model systems to provide mid-points for a design of experiments (DoE) plan which involved manufacture of suspension and solution MDIs with systematically changed formulation variables. The experimental results (e.g., APSD) were used in a lung dosimetry model to explore the relationship between MDI formulation variables and lung deposition. For the BDP solution DoE MDIs, increased concentrations of oleic acid (between 0 and 2% w/w) increased predicted lung deposition whereas changes in ethanol concentration (between 7 and 9% w/w) had no effect on predicted lung deposition. For the AS suspension DoE MDIs, changes in oleic acid concentration (between 0.005 and 0.25% w/w) or micronized drug median particle size (between 1.4 and 2.5 μm) increased predicted lung deposition, whereas predicted lung deposition decreased as ethanol concentration increased from 2 to 20% w/w. These results demonstrate the utility of using dosimetry models to explore relationships between formulation variables and predicted lung deposition and the possibility that these approaches might correlate with in vivo lung deposition.