In Silico Design, Synthesis and Evaluation of Edaravone Co-Crystals with Improved Aqueous Solubility

Posted: 7 Feb 2020

See all articles by Dibyaprava Dash

Dibyaprava Dash

Institute of Pharmacy & Technology

Ajay Kumar Mohapatra

Institute of Pharmacy & Technology

Amaresh Mahapatra

Institute of Pharmacy & Technology

Ashish Kumar Pradhan

Institute of Pharmacy & Technology

Deepak Kumar Sahoo

Biswa Mohan Behera

Institute of Pharmacy & Technology

Sidhartha Sankar Kar

Institute of Pharmacy & Technology

Date Written: February 5, 2020

Abstract

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

Suggested Citation

Dash, Dibyaprava and Mohapatra, Ajay Kumar and Mahapatra, Amaresh and Pradhan, Ashish Kumar and Sahoo, Deepak Kumar and Behera, Biswa Mohan and Kar, Sidhartha Sankar, In Silico Design, Synthesis and Evaluation of Edaravone Co-Crystals with Improved Aqueous Solubility (February 5, 2020). Proceedings of International Conference on Drug Discovery (ICDD) 2020, Available at SSRN: https://ssrn.com/abstract=3531556

Dibyaprava Dash (Contact Author)

Institute of Pharmacy & Technology ( email )

Salipur
Cuttack, OR ODISHA 754202
India

Ajay Kumar Mohapatra

Institute of Pharmacy & Technology ( email )

Salipur
Cuttack, OR ODISHA 754202
India

Amaresh Mahapatra

Institute of Pharmacy & Technology ( email )

Salipur
Cuttack, OR ODISHA 754202
India

Ashish Kumar Pradhan

Institute of Pharmacy & Technology ( email )

Salipur
Cuttack, OR ODISHA 754202
India

Biswa Mohan Behera

Institute of Pharmacy & Technology ( email )

Salipur
Cuttack, OR ODISHA 754202
India
09438278995 (Phone)
754202 (Fax)

Sidhartha Sankar Kar

Institute of Pharmacy & Technology ( email )

Salipur
Cuttack, OR ODISHA 754202
India

No contact information is available for Deepak Kumar Sahoo

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