In vitro evaluation of dry powder inhalers II: influence of carrier particle size and concentration on in vitro deposition

Dry powders and their delivery devices are an alternative to pressurized metered-dose inhalers (pMDI) for the administration of aerosols to the lungs. Generally dry powder aerosols are formulated by mixing a cohesive micronized drug with larger carrier particles resulting in an interactive powder mixture. Redispersion of the drug from agglomerates or the carrier surface during inhalation is a critical factor which greatly influences the fine particle fraction (particles<6.4 μm) to be achieved. Two devices, the single-unit-dose Spinhaler™ (Fisons) and the multiple-unit-dose Easyhaler™ (Orion Pharma) were used to investigate the influence of dry powder formulation on the deposition of interactive mixtures. Following the scheme of a 32-factorial design budesonide was mixed with lactose-α-monohydrate varying the lactose sieve fractions and the drug to carrier proportion. The in vitro deposition of these mixtures was determined using a Twin Stage Impinger (Apparatus A, BP 93) and compared to control experiments performed with unsieved drug carrier. Deposition was found to be highly dependent on the dry powder formulation. Fine particle fractions from 10 up to 50% were observed. The Easyhaler™ shows little differences compared to the Spinhaler™ device.