Abstract：
In this paper, solid-state amorphization induced by mechanical milling is shown to be a useful tool to explore the polymorphism of drugs and their mechanism of devitrification. We show in particular how the recrystallization of amorphous chlorhexidine dihydrochloride obtained by milling reveals a complex polymorphism that involves several polymorphic forms. Two new crystalline forms are identified, one of them appearing as a highly disordered precursor state which however clearly differs from the amorphous one. Several interpretations are here proposed to describe the puzzling nature of this phase. In addition, the possibility to amorphize chlorhexidine dihydrochloride by milling allowed to determine the main physical characters of the amorphous state which cannot be obtained through the usual thermal quench of the liquid because of a strong chemical degradation occurring on melting.
摘要：
在本文中,通过机械研磨诱导的固态非晶化被证明是探索药物多态性及其失透机理的有用工具。我们特别展示了通过研磨获得的无定形氯己定二盐酸盐的重结晶如何揭示涉及几种多晶型形式的复杂多晶型。确定了两种新的晶体形式，其中一种表现为高度无序的前体状态，但与无定形状态明显不同。这里提出了几种解释来描述这一阶段令人困惑的性质。此外,通过研磨使二盐酸氯己定非晶化的可能性允许确定无定形状态的主要物理特征，由于熔融时发生强烈的化学降解，该无定形状态不能通过液体的常规热骤冷获得。
