Formulation strategies, preparation methods, and devices for pulmonary delivery of biologics.

Biological products, including vaccines, blood components, and recombinant therapeutic proteins, are derived from natural sources such as humans, animals, or microorganisms and are typically produced using advanced biotechnological methods. The success of biologics, particularly monoclonal antibodies, can be attributed to their favorable safety profiles and target specificity. However, their large molecular size presents significant challenges in drug delivery, particularly in overcoming biological barriers. Pulmonary delivery has emerged as a promising route for administering biologics, offering non-invasive delivery with rapid absorption, high systemic bioavailability, and avoidance of first-pass metabolism. This review first details the anatomy and physiological barriers of the respiratory tract and the associated challenges of pulmonary drug delivery (PDD). It further discusses innovations in PDD, the impact of particle size on drug deposition, and the use of secondary particles, such as nanoparticles, to enhance bioavailability and targeting. The review also explains various devices used for PDD, including dry powder inhalers (DPIs) and nebulizers, highlighting their advantages and limitations in delivering biologics. The role of excipients in improving the stability and performance of inhalation products is also addressed. Since dry powders are considered the suitable format for delivering biomolecules, particular emphasis is placed on the excipients used in DPI development. The final section of the article reviews and compares various dry powder manufacturing methods, clarifying their clinical relevance and potential for future applications in the field of inhalable drug formulation.