School of Pharmacy, De Montfort University, Leicester, UK.
Eur J Pharm Biopharm. 2013 Apr;83(3):415-26. doi: 10.1016/j.ejpb.2012.10.005. Epub 2012 Nov 16.
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.
共晶在提高难溶性药物的溶解速率和吸收度方面显示出巨大的潜力。然而，共晶的溶液介导的相转变会大大降低其表观溶解度和溶解速率的提高。本研究旨在深入了解共晶在溶解过程中的相变行为，并研究提高溶解速率的方法。通过不同的原位技术，如 UV 成像和拉曼光谱法，研究了卡马西平-烟酰胺（CBZ-NIC）共晶、物理混合物以及不同形式的卡马西平（CBZ I、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 共晶在溶解过程中的固有溶解速率（IDR）下降较慢，表明从溶液中结晶出 CBZ DH 的速率较慢。原位固态特性研究表明，CBZ-NIC 共晶及其多晶型物向二水合物形式的转化。研究表明，原位 UV 成像和拉曼光谱与 SEM 等互补技术的结合，可以深入了解共晶在溶解过程中的行为。
