The Influence of the Formulation and Delivery Approach on the Aerodynamic Performance of Salmeterol Xinafoate

Cláudia Moura, Sofia Silva, Filipe Neves, Ana Aguiar-Ricardo, Eunice Costa

Dry powder inhaler (DPI) systems are conventionally formulated using a carrier-based (CB) approach. The powder performance is highly influenced by the lactose properties, which can be variable, and frequently lead to blend uniformity issues or poor Active Pharmaceutical Ingredient (API) aerosolization. Some of these challenges can be overcome by using alternative technologies such as spray-drying (SD) for preparing inhalable formulations of composite particles (CMP) with enhanced aerodynamic performance (ADP).

Salmeterol xinafoate (SX), a cohesive inhalation API that usually presents poor ADP through the CB approach, was formulated using two DPI strategies, a CB approach where the SX was size reduced by jet milling (JM) until a median particle size (Dv50) of 2.6 µm and blended at 0.4% (w/w) with coarse (Respitose ML001) and fine (Lactohale 300) lactose excipients with a label claim of 50 µg of SX/actuation and a CMP approach in which a water/ethanol solution with 2% (w/w) of solids concentration composed of trehalose(80%), leucine(20%) and SX(0.4%) was SD to generate a dry powder with a label claim of 50 µg of SX/actuation. The ADP was assessed by a Next Generation Impactor (NGI) using a Plastiape HR model 7 device at 60 L/min for both DPIs. The deposition profiles were also compared to a SX suspension metered dose inhaler (MDI) formulation, with a label claim of 36.3 µg of SX/actuation, by NGI at 30 L/min.

The ADP of the two DPI powders showed that although a similar emitted dose (ED) was obtained, the CMP presented a fine particle fraction < 5 µm relative to the ED (FPFED) of 90%; three times higher than the CB powder and 1.5 times higher than the MDI formulation. It was concluded that the production of CMP by SD clearly shows a superior performance relative to the other classical approaches. This strategy is especially advantageous for potent APIs that can be difficult to formulate as DPIs.

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