Co-crystals of non-steroidal anti-inflammatory drugs (NSAIDs): Insight toward formation, methods, and drug enhancement--颗粒学报PARTICUOLOGY

Nascimento, A. L. C. S., Fernandes, R. P., Charpentier, M. D., ter Horst, J. H., Caires, F. J., & Chorilli, M. (2021). Co-crystals of non-steroidal anti-inflammatory drugs (NSAIDs): Insight toward formation, methods, and drug enhancement. Particuology, 58, 227-241. https://doi.org/10.1016/j.partic.2021.03.015

Co-crystals of non-steroidal anti-inflammatory drugs (NSAIDs): Insight toward formation, methods, and drug enhancement

André L.C.S. Nascimento ^a *, Richard P. Fernandes ^b, Maxime D. Charpentier ^c, Joop H. ter Horst ^c, Flávio J. Caires ^d, Marlus Chorilli ^a

a São Paulo State University (UNESP), School of Pharmaceutical Sciences, 14800–903 Araraquara, São Paulo, Brazil
b São Paulo State University (UNESP), Institute of Chemistry, 14800–060 Araraquara, São Paulo, Brazil
c EPSRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation, University of Strathclyde, Glasgow, UK
d São Paulo State University (UNESP), School of Sciences, 17033–260 Bauru, São Paulo, Brazil

10.1016/j.partic.2021.03.015

Volume 58, October 2021, Pages 227-241

Received 17 December 2020, Revised 16 March 2021, Accepted 31 March 2021, Available online 24 April 2021, Version of Record 3 May 2021.

E-mail: nascimento.a.l.c@gmail.com

Highlights

• Different solid phases with new thermodynamic, mechanical, and kinetic properties.

• Promising results on in vitro/in vivo were highlighted.

• Nicotinamide and derivatives are by far the most preferred choice of co-formers.

• LAG has shown to be upper to solvent-free methods on NSAIDs co-crystals.

• Some phase III clinical trials show greater analgesic and anti-inflammatory activity.

Abstract

Pharmaceutical co-crystals have been explored by many researchers as a strategy to optimize physicochemical properties of solid-state drugs. Their improvements of solubility, bioavailability, and the reduced tendency for phase transformation occurrence, are factors that highlight benefits of pharmaceutical co-crystals among other solid forms. According to the Biopharmaceutical Classification System (BCS), non-steroidal anti-inflammatory drugs (NSAIDs) are class II drugs, which have low aqueous solubility and therefore co-crystallization has the potential to optimize NSAID product properties. In this review, we highlight the recent progress made on NSAIDs co-crystals, their co-formers, synthesis, methods and use, while we underline some promising results on in vitro and in vivo co-crystal properties. A celecoxib-tramadol co-crystal reaches phase III clinical trials, showing greater analgesic activity than both individual APIs. The aqueous solubility of the co-crystal formed between l-proline and diclofenac is very high in comparison with the pure drug. Naproxen co-crystals with urea and thiourea have an increase of drug release of almost 60%. Co-crystal design brings a new perspective in drug development since the co-former used can also be a biologically active component allowing to combine different anti-inflammatory drugs, which have an incredible spectrum of application due to the analgesic, anti-pyretic and anti-inflammatory properties.

Graphical abstract

Keywords

Pharmaceutical co-crystals; NSAIDs; Supramolecular synthons; Co-crystal discovery; Bioavailability

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