McTague Hannah, Rasmuson Åke C
Synthesis and Solid State Pharmaceutical Centre (SSPC), Bernal Institute, Department of Chemical and Environmental Science, University of Limerick, Limerick V94 T9PX, Ireland.
Department of Chemical Engineering and Technology, KTH Royal Institute of Technology, Stockholm SE-100 44, Sweden.
Cryst Growth Des. 2023 Sep 1;23(10):7053-7065. doi: 10.1021/acs.cgd.2c01522. eCollection 2023 Oct 4.
The nucleation in the -hydroxybenzoic acid:glutaric acid 1:1 cocrystal (PHBA:GLU) system has been investigated in stoichiometric and non-stoichiometric acetonitrile solutions by induction time experiments. Utilizing the ternary phase diagram, the supersaturated non-stoichiometric solutions were created with compositions along the invariant point boundary lines. In all cases, the PHBA:GLU cocrystal was the nucleating phase, even though the non-stoichiometric solutions were also supersaturated with respect to the pure solid phases. The nucleation of the cocrystal from the mixed solutions is found to be more difficult than the nucleation of the pure compounds from the respective pure solutions, as captured by lower pre-exponential factors (). However, if the driving force is defined per reactant molecule instead of per heterodimer, the cocrystal nucleation difficulty is close to that of the more difficult-to-nucleate pure compound. The difference in nucleation difficulty of the cocrystal from stoichiometric and non-stoichiometric solutions was captured by differences in the interfacial energy, while the pre-exponential factor remained unchanged. Apart from the pure GLU system, the relation between the experimentally determined pre-exponential factors for the different systems correlates with calculated values using theoretical expressions for volume-diffusion and surface-integration control.
通过诱导时间实验，在化学计量和非化学计量的乙腈溶液中研究了对羟基苯甲酸：戊二酸1:1共晶体（PHBA:GLU）体系中的成核现象。利用三元相图，制备了沿不变点边界线组成的过饱和非化学计量溶液。在所有情况下，即使非化学计量溶液相对于纯固相也过饱和，但PHBA:GLU共晶体仍是成核相。发现从混合溶液中形成共晶体的成核过程比从各自的纯溶液中形成纯化合物的成核过程更困难，这通过较低的指前因子（）得以体现。然而，如果驱动力是按每个反应物分子而不是每个异二聚体来定义，共晶体成核难度就接近较难成核的纯化合物的成核难度。化学计量和非化学计量溶液中共晶体成核难度的差异通过界面能的差异得以体现，而指前因子保持不变。除了纯GLU体系外，不同体系实验测定的指前因子之间的关系与使用体积扩散和表面整合控制的理论表达式计算的值相关。
