Department of Pharmacy , University of Copenhagen , Universitetsparken 2 , 2100 Copenhagen , Denmark.
School of Functional Food and Wine , Shenyang Pharmaceutical University , Wenhua Rd. 103 , Shenyang 110016 , China.
Mol Pharm. 2019 Mar 4;16(3):1294-1304. doi: 10.1021/acs.molpharmaceut.8b01229. Epub 2019 Jan 25.
The formation of co-amorphous and co-crystal systems are attractive formulation strategies for poorly water-soluble drugs. Intermolecular interactions between the drug and the coformer(s) play an important role in the formation of both systems, making the investigation of transformations between the two systems specifically interesting. The aim of this study thus was to investigate the transformation between the two systems and its influence on the formation and physical stability of co-amorphous systems. Carbamazepine (CBZ) along with benzoic acid, maleic acid, succinic acid, tartaric acid, saccharin, and nicotinamide were used as materials. First, CBZ- co-former co-crystals were prepared. Then the co-crystals and CBZ- co-former physical mixtures were ball milled to investigate the possible co-amorphization process. The XRPD and DSC results showed that CBZ and coformers tended to maintain (co-crystals as the starting material) or form co-crystals (physical mixtures as the starting material), rather than to form co-amorphous systems. Next, co-amorphization from CBZ- co-former physical mixtures via quench cooling was studied. While co-amorphous systems were obtained, the physical stability of these was very low, and the samples recrystallized to either co-crystal forms or the individual components. In conclusion, a possible transformation between the two systems was confirmed, but the resulting co-amorphous systems were highly unstable.
共无定形和共晶系统的形成是提高疏水性药物溶解度的有吸引力的制剂策略。药物与共晶形成剂之间的分子间相互作用在这两种系统的形成中起着重要作用，因此研究两种系统之间的转化特别有趣。本研究的目的是研究两种系统之间的转化及其对共无定形系统形成和物理稳定性的影响。使用卡马西平（CBZ）与苯甲酸、马来酸、琥珀酸、酒石酸、糖精和烟酰胺作为材料。首先，制备 CBZ-共晶形成剂共晶。然后将共晶和 CBZ-共晶物理混合物进行球磨，以研究可能的共无定形化过程。XRPD 和 DSC 结果表明，CBZ 和共晶形成剂倾向于保持（以共晶为起始材料）或形成共晶（以物理混合物为起始材料），而不是形成共无定形系统。接下来，通过骤冷研究了 CBZ-共晶形成剂物理混合物的共无定形化。虽然获得了共无定形系统，但这些系统的物理稳定性非常低，样品会重新结晶为共晶形式或单个成分。总之，证实了两种系统之间的一种可能转化，但得到的共无定形系统极不稳定。
