This review focuses on identifying the primary limitations affecting the oral administration of biologics and evaluates current strategies designed to improve their bioavailability. It also incorporates a bibliometric mapping approach to assess ongoing research trends in this field. A detailed literature survey was performed alongside a bibliometric analysis using VOSviewer to illustrate keyword relationships and the evolution of research activity in oral biologic delivery. Barriers such as enzymatic degradation, restricted epithelial transport, and rapid systemic elimination hinder effective oral delivery of biologics. Innovative approaches including nanocarrier systems, enteric coatings, PEGylation, lipidation, protease inhibitors, and mucoadhesive formulations have been developed to address these issues. Advances like receptor targeted ligand systems and pH sensitive nanocarriers show promise for more efficient absorption. Emerging therapies, including GLP-1 receptor agonists and orally delivered monoclonal antibodies, are highlighted. The review also touches upon therapeutic applications beyond oncology, such as neurodegenerative diseases. Case studies on oral insulin provide valuable clinical development insights. Scaleup production and regulatory challenges are discussed, along with future directions for formulation improvement. Although oral delivery of biologics presents significant obstacles, technological advancements are steadily transforming the landscape. Future research focusing absorption mechanisms and innovative formulation strategies will be crucial for the successful development of effective oral biologic therapies.
