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

Nascimento, André L.C.S. and Fernandes, Richard P. and Charpentier, Maxime D. and ter Horst, Joop H. and Caires, Flávio J. and Chorilli, Marlus (2021) Co-crystals of non-steroidal anti-inflammatory drugs (NSAIDs) : insight toward formation, methods, and drug enhancement. Particuology, 58. pp. 227-241. ISSN 2210-4291 (https://doi.org/10.1016/j.partic.2021.03.015)

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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.

ORCID iDs

Nascimento, André L.C.S., Fernandes, Richard P., Charpentier, Maxime D., ter Horst, Joop H. ORCID logoORCID: https://orcid.org/0000-0003-0118-2160, Caires, Flávio J. and Chorilli, Marlus;
CORE (COnnecting REpositories)