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  • Title: In situ monitoring of carbamazepine-nicotinamide cocrystal intrinsic dissolution behaviour.
    Author: Qiao N, Wang K, Schlindwein W, Davies A, Li M.
    Journal: Eur J Pharm Biopharm; 2013 Apr; 83(3):415-26. PubMed ID: 23159709.
    Abstract:
    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.
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