Design of inhaled insulin dry powder formulations to bypass deposition in the human extrathoracic region and enhance lung targeting

Abstract

The effectiveness of aerosol drug delivery to the lungs depends on both the drug formulation and device. Currently marketed inhalation drug products often deliver no more than 15 – 30% of the packaged dose to the lung, either due to losses in the inhaler device, or deposition in the patient’s mouth-throat. This poses a significant challenge in the development of inhalation drugs, as it can dictate higher nominal doses in order to compensate for losses, and can result in increased systemic exposure for drugs that are orally bioavailable and, in some instances, increases in local and systemic side effects (e.g., for inhaled corticosteroids). In addition, large extrathoracic region losses can lead to increased variance in dose delivery to the lung. The goal of this research was to demonstrate that for dry powder inhalers, improved targeting to the lungs may be achieved by tailoring the micromeritic properties of the particles (e.g., size, density, and rugosity) to reduce deposition in the mouth and throat to negligible levels, thereby maximizing the total dose delivered to the lung. This can be achieved by co-solvent spray drying approach to modulate particle morphology and dose delivery characteristics of engineered powder formulations.