Celecoxib:Nicotinamide Dissociation: Using Excipients To Capture the Cocrystal's Potential

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• 作者：Julius F. Remenar ; Matthew L. Peterson ; Peter W. Stephens ; Zhong Zhang ; Yuri Zimenkov ; Magali B. Hickey
• 刊名：Molecular Pharmaceutics
• 出版年：2007
• 出版时间：June 2007
• 年：2007
• 卷：4
• 期：3
• 页码：386 - 400
• 全文大小：1067K
• 年卷期：v.4,no.3(June 2007)
• ISSN：1543-8392

文摘

The cocrystal of celecoxib and nicotinamide (Cel:Nic) was crystallized from chloroformin a 1:1 ratio, and the structure has been solved from powder X-ray diffraction data. Thedissolution and solubility of Cel:Nic are medium dependent and can be attributed to differencesin conversion of Cel:Nic to celecoxib polymorphs I and III (Cel-I and Cel-III). The presence oflow concentrations of surfactants facilitates the rapid conversion of neat Cel:Nic to largeaggregates of Cel-III that dissolve more slowly than commercial Cel-III into 1% SDS solution.In contrast, combinations of Cel:Nic with both 1-10% solid SDS and PVP wet rapidly and convertto a mixture of amorphous celecoxib and a micron-sized crystalline celecoxib form IV (Cel-IV),which has recently been shown to be up to 4-fold more bioavailable than marketed Cel-III. Morethan 90% of the suspended material dissolves within 2 min at 37 f">C when transferred to 1%SDS solution. This example highlights the importance of exploring the form conversion ofcocrystals in aqueous media prior to pharmacokinetic studies, and illustrates the potential ofsimple formulations to overcome the limitations caused by rapid dissociation of cocrystals andrecrystallization of poorly soluble forms in aqueous media.