[Development of an Inhalation Dry Powder Preparation Method without Heat-drying Process].

Biopharmaceuticals, including therapeutic genes and proteins, are characterized by highly-targeted, specific action and flexible pharmacological design and have a rapidly growing market share; however, because of high molecular weight and low stability, injection is the most common delivery route of biopharmaceuticals. Thus, pharmaceutical innovations are required to provide alternative delivery routes for biopharmaceuticals. Pulmonary drug delivery via inhalation is a promising approach, particularly for targeting local diseases of the lung, because it can exert therapeutic effects in small doses and can noninvasively and directly deliver drugs to airway surfaces. However, biopharmaceutical inhalers must ensure that the biopharmaceuticals maintain their integrity as they are subjected to several types of physicochemical stress, such as hydrolysis, ultrasound, and heating, at various stages during the process from manufacturing to administration. In this symposium, I present a novel dry powder inhaler (DPI) preparation method without heat-drying, with the goal of developing biopharmaceutical DPIs. Spray-freeze-drying is a nonthermal drying technique that produces a powder with porous shapes; this powder has suitable inhalation characteristics for DPI. A model drug, plasmid DNA (pDNA), was stably prepared as a DPI using the spray-freeze-drying process. Under dry conditions, the powders maintained high inhalation characteristics and maintained pDNA integrity for 12 months. The powder induced pDNA expression in mouse lungs that exceeded at higher levels than the solution did. This novel preparation method is suitable for DPI preparation for various drugs and may help expand the clinical application of DPIs.