Celecoxib:Nicotinamide dissociation:: Using excipients to capture the cocrystal's potential
Celecoxib:Nicotinamide dissociation:: Using excipients to capture the cocrystal's potential
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DOI：
10.1021/mp0700108
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发表时间：
2007-05-01
影响因子：
4.9
通讯作者：
Hickey, Magali B.
中科院分区：
文献类型：
--
作者：
Remenar, Julius F.;Peterson, Matthew L.;Hickey, Magali B.
从氯仿中以1：1的比例结晶出塞来昔布和烟酰胺的共晶体（Cel：Nic），并且已经从粉末X射线衍射数据解析了结构。Cel：Nic的溶出度和溶解度具有介质依赖性，可归因于Cel：Nic向塞来昔布多晶型物I和III（Cel- I和CeI-III）转化的差异。低浓度表面活性剂的存在促进纯Cel：Nic快速转化为Cel- III的大聚集体，其比商业Cel- III更慢地溶解在1%SDS溶液中。相比之下，CeI：Nic与1-10%固体SDS和PVP的组合快速润湿并转化为无定形塞来昔布和微米级结晶塞来昔布IV型（CeI-IV）的混合物，最近已显示其生物利用度比市售CeI-III高4倍。当转移到1%SDS溶液中时，超过90%的悬浮材料在37 ℃下2分钟内溶解。该实施例强调了在药代动力学研究之前探索共晶在水性介质中的形式转化的重要性，并说明了简单制剂克服由共晶的快速解离和水介质中难溶形式的重结晶引起的限制的潜力。
The cocrystal of celecoxib and nicotinamide ( Cel: Nic) was crystallized from chloroform in a 1: 1 ratio, and the structure has been solved from powder X- ray diffraction data. The dissolution and solubility of Cel: Nic are medium dependent and can be attributed to differences in conversion of Cel: Nic to celecoxib polymorphs I and III (Cel- I and CeI-III). The presence of low concentrations of surfactants facilitates the rapid conversion of neat Cel: Nic to large aggregates of Cel- III that dissolve more slowly than commercial Cel- III into 1% SDS solution. In contrast, combinations of CeI: Nic with both 1-10% solid SDS and PVP wet rapidly and convert to a mixture of amorphous celecoxib and a micron-sized crystalline celecoxib form IV (CeI- IV), which has recently been shown to be up to 4-fold more bioavailable than marketed CeI-III. More than 90% of the suspended material dissolves within 2 min at 37 degrees C when transferred to 1% SDS solution. This example highlights the importance of exploring the form conversion of cocrystals in aqueous media prior to pharmacokinetic studies, and illustrates the potential of simple formulations to overcome the limitations caused by rapid dissociation of cocrystals and recrystallization of poorly soluble forms in aqueous media.