FORMULATION AND EVALUATION OF NOVEL CO-CRYSTALS OF CITALOPRAM HYDROBROMIDE USING A FULL FACTORIAL DESIGN APPROACH

*R. Sachithananthan, G. N. A. Lakshmi

Background: Citalopram Hydrobromide, a selective serotonin reuptake inhibitor (SSRI), exhibits limited aqueous solubility, restricting its bioavailability. Co-crystallization has emerged as a promising approach to enhance solubility and dissolution without chemical modification. To formulate and evaluate co-crystals of Citalopram Hydrobromide with different co-formers (urea, citric acid, tartaric acid) in molar ratios of 1:2 and 1:3, and to assess their impact on solubility, dissolution rate, and tablet formulation performance. Methods: Co-crystals were prepared using the co-grinding method and characterized by UV, FTIR, PXRD, melting point, saturation solubility, and electron microscopy. Tablets were prepared by wet granulation, optimized using 2² full factorial design, and evaluated for weight variation, hardness, friability, disintegration, and in vitro dissolution. Results: Co-crystals with tartaric acid (1:3) showed the highest drug content (98.89%), saturation solubility (0.809 mg/ml), and dissolution (100.2% in 60 min). Among 12 tablet formulations, F11 (tartaric acid 1:3) demonstrated superior performance with optimal disintegration and dissolution profiles. Conclusion: Co-crystallization significantly improved the physicochemical properties of Citalopram Hydrobromide. Tartaric acid (1:3) co-crystal tablets showed the most promising results, offering a simple and effective approach to enhance oral bioavailability of poorly soluble drugs.