Co-spray dried lipid-based dry powder for inhalation for systemic delivery of analgesics: solid state and aerodynamic assessment

C Corzo


Despite of their challenging solid state behaviour, lipid-based excipients (LBE) are widely used matrixes for modified drug release in oral and dermal formulations. The biodegradability of LBE offer a beneficial platform for local and systemic pulmonary drug delivery. For these, readily inhalable and highly engineered lipid particles are desirable. Spray drying is the most versatile manufacturing process for particle engineering, however the low-melting points, polymorphism and phase transitions of LBE impair the process and product performance. Strong knowledge on the solid state of LBE can provide a rational design for controlling phase transitions and overcoming these impairments. In this research, the solid state of a LBE-drug system was assessed. The findings were applied to select suitable process parameters of conventional spray drying. The final formulation is envisaged as a co-spray dried lipid-based DPI for systemic delivery of analgetics with modified release for acute pain therapy, when an oral medication is not possible. Glyceryl dibehenate (GD) and Ibuprofen (IBU) were used as model LBE and model drug, respectively. The solid state assessment of GD:IBU system revealed melting point depression without polymorphic transitions. Solid-liquid (S-L) regions and temperature boundaries were established and applied to spray drying. An outlet temperature below the S-L region was achieved, consequently powder was successfully collected. The produced powder showed promising in vitro performance with geometric diameter of 5.070µm, MMAD of 4.491µm and FPF of 37.4%. This research comprises a platform for optimizing conventional spray drying to manufacture lipid-based DPI based on a rational solid state assessment.

Key Message

The solid state assessment of a system comprising a lipid-based excipient and a drug provides a rational platform to set process temperature boundaries and circumvent lipid polymorphic transitions during spray drying. Thereby non-inhalable sticky particles are evaded and lipid-based DPIs with advanced performance can be manufactured via conventional spray drying.

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