Cocrystals of telmisartan with ascorbic acid: Enhanced solubility and antiviral potency against Japanese encephalitis virus.

The significant impact of Japanese encephalitis virus (JEV) on society and the lack of any approved antiviral drugs demand urgent attention. Considering the prohibitive cost involved in new antiviral development, repurposing existing drugs is an alternative strategy. Telmisartan (TM) is a prime candidate for repurposing against JEV due to its ability to inhibit JEV infection. Poor aqueous solubility of TM can be a major hurdle in harnessing its repurposing against JEV. Cocrystallization with appropriate coformers has the scope to improve solubility and antiviral properties. Ascorbic acid (Asca), with its proven efficacy as an adjuvant to antivirals, was used as a coformer to develop a cocrystal with TM (1:1) using a novel microwave-assisted synthesis method. From FTIR, NMR, and DSC data, supported by XRD, confirmed the formation of the cocrystal. The 1H NMR supported the 1:1 stoichiometry. The cocrystal showed adequate stability under refrigeration conditions. Using valid analytical methods, the solubility of the cocrystal was found to be enhanced by 81-fold compared to TM. The significant increase in solubility was also associated with a significant enhancement in ex vivo intestinal permeability of the cocrystal (60%) compared to that of TM (28%). Antiviral assay revealed a 2-fold enhancement in the potency of the cocrystal. This was also associated with a significant increase in selectivity index (29) as compared to TM (14.18), indicating its enhanced antiviral properties. Cocrystallization with Asca enhanced solubility, ex vivo permeability, and antiviral properties of TM, which can encourage its further progress with validation in preclinical and clinical conditions.