Spray-Dried Phospholipid Porous Particles for Inhalation - Product Quality Studies

Spray-dried phospholipid porous particles (PPPs) are lipid-based microparticles with low density attributed to their nanosized porous structure. PPPs are increasingly used in orally inhaled drug products (OIDPs) for higher drug loading, improved dose uniformity, and deeper lung deposition as compared to traditional OIDPs (e.g., drug-lactose mixture). Manufacturing of this emerging and complex new formulation involves the preparation of nanoemulsions as the feedstock and spray drying the feedstock to generate PPPs in a dry powder form. Single or multiple active pharmaceutical ingredients can be incorporated with the spray-dried PPPs and filled into metered-dose inhalers (MDIs) or dry powder inhalers (DPIs) for pulmonary drug delivery. Understanding the manufacturing process to identify critical process parameters that affect critical quality attributes (CQAs) of PPPs are crucial for informing the development of product-specific guidance (PSG) for generic drug products with PPPs. In addition, this study will provide information for FDA reviewers in evaluating NDA submissions of new OIDPs with the PPPs platform and update the current guidance for quality considerations of MDI and DPI drug products.

This presentation will introduce FDA approaches in understanding the manufacturing process and characterization techniques for PPPs. Through in-house manufacturing of PPPs based on the design-of-experiment (DOE) principle, we identified critical process parameters in the nanoemulsion preparation and spray drying processes. During the nanoemulsion preparation using a microfluidics device, chamber geometry, chamber pressure, and number of passes for the coarse emulsion were found to significantly influence the globule size distribution and stability of the nanoemulsion. During the spray drying process, air flow rate, inlet temperature, and concentration of the feedstock nanoemulsion were found to significantly influence the morphology, moisture content, and particle size distribution of the dry powders. In summary, these process parameters are considered critical to the product quality of PPPs, and hence need to be appropriately controlled.