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

作　　者：Andre L.C.S.Nascimento Richard P.Fernandes Maxime D.Charpentier Joop H.ter Horst Flavio J.Caires Marius Chorilli 

机构地区：[1]Sao Paulo State University(UNESP),School of Pharmaceutical Sciences,14800-903 Araraquara,Sao Paulo,Brazil [2]São Paulo State University(UNESP),Institute of Chemistry,14800-060 Araraquara,Sao Paulo,Brazil [3]EPSRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation,University of Strathclyde,Glasgow,UK [4]Sao Paulo State University(UNESP),School of Sciences,17033-260 Bauru,Sao Paulo,Brazil

出　　处：《Particuology》2021年第5期227-241,共15页颗粒学报（英文版）

基　　金：FAPESP(Proc.n 2013/09022-7,2017/14936-9,2018/12463-9,2018/24378-6 and 2018/23357-5);CNPq(Proc.141829/2017-6)for financial support;the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No.722456 CORE ITN for funding as part of the CORE project(October 2016-September 2020);the EPSRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallization(http://www.cmac.ac.uk)for supporting this work(EPSRC funding under Grant Reference:EP/1033459/1).

摘　　要：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.

关 键 词：Pharmaceutical co-crystals NSAIDS Supramolecular synthons Co-crystal discovery BIOAVAILABILITY 

分 类 号：R97[医药卫生—药品]