Exploration of Pharmaceutical Cocrystals of Zaltoprofen: Development, Physicochemical Characterization, and Enhancement of Solubility and Dissolution Behavior

Abstract

Biopharmaceutics Classification System (BCS) Class II drugs are characterized by low aqueous solubility, which can limit dissolution and oral absorption. Zaltoprofen is a non-steroidal anti-inflammatory drug with a hydrophobic structure and limited aqueous solubility. Pharmaceutical cocrystallization offers a solid-state strategy for modifying lattice packing and physicochemical properties without altering the covalent structure of the active pharmaceutical ingredient. This review summarizes principles of cocrystal design, coformer selection, preparation methods, solid-state characterization, and the effects of cocrystallization on solubility and dissolution behavior, with particular emphasis on zaltoprofen. Solution-based crystallization, mechanochemical approaches such as liquid-assisted grinding, and emerging continuous-processing approaches including hot-melt extrusion are discussed. The review also emphasizes that improved dissolution is not guaranteed and may be limited by lattice stability, supersaturation loss, or solution-mediated phase transformation. Translational success will therefore depend on rational coformer selection, robust solid-state characterization, scalable manufacturing, and appropriate in vitro and in vivo validation. The review further considers the use of coformers such as nicotinamide and 4,4′-bipyridine, while emphasizing that dissolution enhancement is system-dependent and must be demonstrated experimentally. Keywords: Zaltoprofen, Pharmaceutical cocrystals, BCS class II drug , Solubility Enhancement