A new Febuxostat-Telmisartan Drug-Drug Cocrystal for Gout-Hypertension Combination Therapy

Drug-drug cocrystalllization is a novel mechanism for effective pharmacological combination therapy. In this work, we have demonstrated the preparation of a drug-drug cocrystal of a hypertension drug (Telmisar-tan; TEL) with a hyperuricemia drug (Febuxostat; FEB) in 1:1 molar ratio using a solvent evaporation method for the first time. Generally, a multi-component system may yield either a eutectic, salt, and/or a cocrystal. This study adopted a methodical orthogonal framework to analyze the final solid form. A single crystal X-ray structural investigation revealed the formation of a heterosynthon with carboxylic and benzimidazole groups of FEB and TEL, respectively, in the triclinic P-1 space group. DpKa of the heterosynthon is >> 1.5, hence, based on the empirical rules, a salt-cocrystal continuum is hypothesized. Further, attenuated total reflectance Four-ier transform infrared (ATR-FTIR), and Raman spectroscopy were employed to corroborate the hydrogen bond formation in the heterosynthon (-N-H-O-), which confirmed the propensity for cocrystal formation. An accelerated stability study and an in vitro biorelevant dissolution study of the cocrystal were performed, which demonstrated that it is physiochemically stable, but it resulted in a slower dissolution rate when com-pared with plain drugs. (c) 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.

Automated summary

Drug-drug cocrystallization was demonstrated for the first time in this study, showing signs of heterosynthon formation in structural analysis. Experimental results indicated specific and limited stability and dissolution rate properties of the cocrystal.