Synthesis, Crystal Structure, and Solubility Analysis of a Famotidine Cocrystal

• Main Authors: Yan Zhang, Zhao Yang, Shuaihua Zhang, Xingtong Zhou
• Format: Article
• Language: English
• Published: MDPI AG 2019-07-01
• Series: Crystals
• Subjects: cocrystal; famotidine; malonic acid; crystal structure; solubility
• Online Access: https://www.mdpi.com/2073-4352/9/7/360

A novel cocrystal of the potent H₂ receptor antagonist famotidine (FMT) was synthesized with malonic acid (MAL) to enhance its solubility. The cocrystal structure was characterized by X-ray single crystal diffraction, and the asymmetry unit contains one FMT and one MAL connected via intermolecular hydrogen bonds. The crystal structure is monoclinic with a P21/n space group and unit cell parameters a = 7.0748 (3) Å, b = 26.6502 (9) Å, c = 9.9823 (4) Å, α = 90, β = 104.2228 (12), γ = 90, V = 1824.42 (12) ų, and Z = 4. The cocrystal had unique thermal, spectroscopic, and powder X-ray diffraction (PXRD) properties that differed from FMT. The solubility of the famotidine-malonic acid cocrystal (FMT-MAL) was 4.2-fold higher than FMT; the FAM-MAL had no change in FMT stability at high temperature, high humidity, or with illumination.