Breaking Barriers: Next-Generation Strategies For Enhancing Solubility And Permeability Of Poorly Bioavailable Drugs

Abstract

The bioavailability of numerous active pharmaceutical ingredients (APIs) is limited by poor aqueous solubility and low permeability, posing significant challenges in drug development. This review examines cutting – edge techniques to overcome these obstacles, focusing on the interplay between solubility and permeability in oral absorption and systemic exposure. We assess ten innovative solubility-enhancement strategies, including solid dispersions, amorphous formulations, co-crystals, lipid-based systems, and cyclodextrin inclusion complexes, as well as ten advanced permeability - boosting approaches. Such as prodrugs, absorption enhancers, nanocarriers, and mucoadhesive systems. Each technique is illustrated with examples, highlighting its mechanistic rationale, formulation considerations, and recent successes. The concludes by discussing hybrid systems that combine solubility and permeability improvement and recommends future research directions. By providing a unified framework for diverse innovations, this review aims to guide researchers toward next-generation solutions that effectively overcome drug bioavailability barriers.