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

Particuology 2021年第5期19卷 227-241页

作者： Andre L.C.S.Nascimento Richard P.Fernandes Maxime D.Charpentier Joop H.ter Horst Flavio J.Caires marius chorilli Sao Paulo State University(UNESP) School of Pharmaceutical Sciences14800-903 AraraquaraSao PauloBrazil São Paulo State University(UNESP) Institute of Chemistry14800-060 AraraquaraSao PauloBrazil EPSRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation University of StrathclydeGlasgowUK Sao Paulo State University(UNESP) School of Sciences17033-260 BauruSao PauloBrazil

Pharmaceutical co-crystals have been explored by many researchers as a strategy to optimize physicochemical properties of solid-state *** improvements of solubility,bioavailability,and the reduced tendency for phase transformation occurrence,are factors that highlight benefits of pharmaceutical co-crystals among other solid *** 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 *** 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 *** aqueous solubility of the co-crystal formed between l-proline and diclofenac is very high in comparison with the pure *** 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.

关键词： Pharmaceutical co-crystals NSAIDs Supramolecular synthons Co-crystal discovery Bioavailability

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