In Silico Design, Synthesis and Evaluation of Edaravone Co-Crystals with Improved Aqueous Solubility
Posted: 7 Feb 2020
Date Written: February 5, 2020
Edaravone, the first treatment for amyotrophic lateral sclerosis (ALS) was approved by the U.S. Food and Drug Administration (FDA) recently. Edaravone is coming under Biopharmaceutics Classification System (BCS) Class IV drug, suffers from poor aqueous solubility and hence low bioavailability. It cannot be developed into oral pharmaceutical formulations due to its poor aqueous solubility. One of the ways to enhance the aqueous solubility of poorly water-soluble drugs is to use the principles of crystal engineering to formulate cocrystals with water-soluble coformers. The aim of the present work was to design, synthesize, characterize and evaluate the aqueous solubility of edaravone co-crystals. Computational techniques were applied for co-crystal screening using coformers like salicylic acid, cinnamic acid, and ascorbic acid against edaravone. All the designed co-crystals were synthesized by fusion method and characterized by UV, FT-IR and melting point data. A shift in the IR peaks with diminished intensity was observed for all the prepared co-crystals with absence of additional peaks. Melting point data showed a decrease in the heat of fusion and melting point in the co-crystals. Aqueous solubility of the co-crystals was determined using UV-Vis spectroscopy. All the three co-crystals demonstrated enhanced aqueous solubility which was superior to the aqueous solubility of pure drug edaravone. Overall, these results demonstrated a consolidated account of the rationale for design of edaravone cocrystals with improved aqueous properties.
Keywords: Edaravone, Co-crystals, Co-formers, In silico design, Fusion technique, Solubility
JEL Classification: 123
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