Development and Evaluation of a Plumbagin-Brinzolamide Binary Cocrystals for Improved Aqueous Solubility

Research Article

Abstract

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) is a secondary metabolite which exhibit antioxidant, anti-inflammatory, and anticancer properties. Although therapeutically active, its clinical application is limited due to its poor aqueous solubility, which leads to suboptimal oral bioavailability and rapid systemic clearance. This research work aimed at the fabrication of a novel pharmaceutical cocrystal involving plumbagin and brinzolamide (PLB–BRZ) as an intervention to alter the physicochemical limitations of the parent phytoconstituent. The preparation of cocrystals involved three distinct approaches: neat grinding, liquid-assisted grinding, and solution crystallization across multiple stoichiometric ratios. Solid-state characterization of prepared cocrystals was carried out using Fourier Transform Infrared Spectroscopy (FTIR), Powder X-ray Diffraction (PXRD), Scanning Electron Microscopy (SEM), and Thermogravimetric Analysis (TGA) and the tests confirmed the formation of a distinct crystalline phase characterized by unique supramolecular synthons. Saturation solubility experiments in diverse media, including distilled water, 0.1 N HCl, and pH 6.8 phosphate buffer, revealed that the cocrystal prepared via solution crystallization (1:1 ratio) achieved a solubility increase exceeding 120% compared to pure plumbagin. These results show that the addition of plumbagin into a multicomponent crystalline lattice with brinzolamide effectively alters the hydration energy and lattice strength, providing a viable pathway for the development of high-performance botanical formulations. The results support the utility of supramolecular chemistry in overcoming the inherent delivery challenges associated with hydrophobic naphthoquinones