Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
Mol Pharm. 2022 Sep 5;19(9):3199-3205. doi: 10.1021/acs.molpharmaceut.2c00339. Epub 2022 Jul 25.
Water is generally regarded as a universal plasticizer of amorphous drugs or amorphous drug-containing systems. A decrease in glass-transition temperature () is considered the general result of this plasticizing effect. A recent study exhibits that water can increase the of amorphous prilocaine (PRL) and thus shows an anti-plasticizing effect. The structurally similar drug lidocaine (LID) might show similar interactions with water, and thus an anti-plasticizing effect of water is hypothesized to also occur in amorphous LID. However, the influence of water on the of LID cannot be determined directly due to the very low stability of LID in the amorphous form. It is possible to predict the of LID from a co-amorphous system of PRL-LID using the Gordon-Taylor equation. Interactions were observed between PRL and LID based on the deviations between the experimental s and the s calculated by the conventional use of the Gordon-Taylor equation. A modified use of the Gordon-Taylor equation was applied using the optimal co-amorphous system as a separate component and the excess drug as the other component. The predicted of fully hydrated LID could thus be determined and was found to be increased by 0.9 ± 0.7 K compared with the of water-free amorphous LID. It could be shown that water exhibited a small anti-plasticizing effect on LID.
水通常被认为是无定形药物或无定形含药系统的通用增塑剂。玻璃化转变温度（Tg）的降低被认为是这种增塑作用的一般结果。最近的一项研究表明，水可以增加无定形普鲁卡因（PRL）的 Tg，从而表现出抗塑化作用。结构相似的药物利多卡因（LID）可能与水发生类似的相互作用，因此假设水在无定形 LID 中也具有抗塑化作用。然而，由于 LID 在无定形形式下非常不稳定，无法直接确定水对 LID 的 Tg 的影响。可以使用 Gordon-Taylor 方程从 PRL-LID 的共无定形系统中预测 LID 的 Tg。基于 PRL 和 LID 之间的实验 s 与 Gordon-Taylor 方程常规使用计算出的 s 之间的偏差，观察到了它们之间的相互作用。使用最佳共无定形系统作为单独的组分，将过量药物作为另一个组分，对 Gordon-Taylor 方程进行了修改使用。因此，可以确定完全水合 LID 的预测 Tg，并发现与无水无定形 LID 的 Tg 相比，其增加了 0.9±0.7 K。结果表明，水对 LID 表现出较小的抗塑化作用。
