Advanced Drug Delivery Strategies to Overcome Solubility and Permeability Challenges: Driving Biopharmaceutical Advancements Toward Commercial Success

Oral drug administration is the safest and most convenient route for drug delivery. Nevertheless, solubility and permeability are two major issues regarding drug design; these issues must be addressed to overcome the biopharmaceutical challenges associated with them. Drugs are classified into four groups according to the biopharmaceutical classification system. Furthermore, drugs from BCS class II demonstrate poor solubility; meanwhile, drugs related to BCS class IV show poor solubility along with poor permeability. However, some drugs of BCS class IV are also substrates for p-glycoprotein and CYP3A4. These features lead to issues of bioavailability and reduced patient compliance. Moreover, the anatomical and physiological behavior of the body and physicochemical features of the drug are also associated with compromised bioavailability. All these concerns make it difficult for any formulator to manufacture drugs, and hurdles related to these drugs make it difficult to deliver them to the actual market. Hence, this review aims to summarize the advanced innovative methodologies to get suitable solutions to overcome the limitations associated with solubility and permeability and accordingly improve the drug's bioavailability. Traditional approaches like physical modifications of drugs, i.e., micronization, solid dispersion in carriers, complexation, cryogenic techniques, and supercritical fluid technology; moreover, chemical modifications of drugs, i.e., salt formation, cosolvency, hydrotropy, and prodrug formation, contribute to treating solubility problems. Meanwhile, a few advanced drug delivery strategies, including lipid-based drug delivery systems, polymeric nanocarriers, pharmaceutically engineered crystals, and p-gp efflux pump inhibitors, have been mentioned that aid in improving the drug's stability in diverse bodily environment, enhance solubility along with permeability, and increasing bioavailability, which directly leads to enhanced patient compliance. Incorporating these methods is essential to address solubility and permeability challenges, lower treatment costs, and enhance patient outcomes. Nanobased delivery systems offer significant potential for improving therapeutic effectiveness and patient compliance.