ABSTRACT:
Griseofulvin (GF) is a neutral BCS Class II antifungal medication that has remained the gold-standard treatment for paediatric tinea capitis caused by Microsporum species. However, its therapeutic efficacy is severely impaired by its high crystal lattice energy and absence of hydrogen-bond donors, leading to poor aqueous solubility and highly variable oral bioavailability. As griseofulvin is non-ionizable at physiological pH, traditional methods such as salt formation, are unviable, and overcoming these limitations, demands advanced physical and formulation-based strategies. Poor aqueous solubility is a major challenge for BCS class II drugs, often resulting in poor bioavailability and making them among the most challenging compounds for formulation development. Hence, multiple strategies have been established with an aim of improving solubility, dissolution rate, and oral bioavailability. This review critically assesses the recent approaches by modulating the physicochemical and pharmacokinetic characteristics of griseofulvin to provide a framework for the development of novel formulation strategies. It critically examines advancements on various platforms, such as nanotechnology-based, high-energy amorphous systems, deep eutectic solvents, and advanced complexation techniques. These strategies have demonstrated significant enhancement in solubility, accompanied by marked enhancement in in-vivo exposure. The therapeutic potential of griseofulvin is further suggested to be improved by future directions, such as the exploration of prodrug derivatization strategies.