In situ monitoring of carbamazepine-nicotinamide cocrystal intrinsic dissolution behaviour
In situ monitoring of carbamazepine-nicotinamide cocrystal intrinsic dissolution behaviour
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DOI：
10.1016/j.ejpb.2012.10.005
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发表时间：
2013-04-01
影响因子：
4.9
通讯作者：
Li, Mingzhong
中科院分区：
文献类型：
--
作者：
Qiao, Ning;Wang, Ke;Li, Mingzhong
共晶体在提高难溶性药物的溶出度和吸收方面显示出巨大的潜力。然而，溶液介导的共晶相变会大大降低其表观溶解度和溶解速率的增强。本研究的目的是深入了解共晶溶解过程中的相变行为，并研究溶解速率的提高。通过不同的原位紫外成像和拉曼光谱技术研究了卡马西平烟酰胺（CBZ-NIC）共晶、物理混合物和不同形式的卡马西平：晶型I（CBZ I）、晶型III（CBZ III）和二水合物（CBZ DH）的溶解和转化行为。研究发现，与CBZ III和I相比，CBZ-NIC共晶的固有溶解速率(IDR)在溶解过程中缓慢降低，表明CBZ DH从溶液中结晶的速率较慢。原位固态表征显示了 CBZ-NIC 共晶和多晶型物向二水合物形式转化的演变。研究表明，原位紫外成像和拉曼光谱与 SEM 互补技术可以提供共晶溶解过程的深入了解。 (C) 2012 Elsevier B.V. 保留所有权利。
Cocrystals have shown huge potential to improve the dissolution rate and absorption of a poorly water soluble drug. However, solution mediated phase transformation of cocrystals could greatly reduce the enhancement of its apparent solubility and dissolution rate. The aim of this study is to gain a deep understanding of the phase transition behaviour of cocrystals during dissolution and to investigate the improvement of dissolution rate. Dissolution and transformation behaviour of carbamazepine nicotinamide (CBZ-NIC) cocrystal, physical mixture and different forms of carbamazepine: form I (CBZ I), form III (CBZ III) and dihydrate (CBZ DH) were studied by different in situ techniques of UV imaging and Raman spectroscopy. It has been found that compared with CBZ III and I, the rate of intrinsic dissolution rate (IDR) of CBZ-NIC cocrystal decreases slowly during dissolution, indicating the rate of crystallisation of CBZ DH from the solution is slow. In situ solid-state characterisation has shown the evolution of conversion of CBZ-NIC cocrystal and polymorphs to its dihydrate form. The study has shown that in situ UV imaging and Raman spectroscopy with a complementary technique of SEM can provide an in depth understanding during dissolution of cocrystals. (C) 2012 Elsevier B.V. All rights reserved.