Effects of a structurally related substance on the crystallization of paracetamol
Effects of a structurally related substance on the crystallization of paracetamol
复制标题
结构相关物质对扑热息痛结晶的影响
DOI：
10.1007/s11705-013-1308-7
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发表时间：
2013
影响因子：
4.5
通讯作者：
Z. Nagy
中科院分区：
文献类型：
--
作者：
A. N. Saleemi;I. I. Onyemelukwe;Z. Nagy
对乙酰氨基酚（PCM）从异丙醇（IPA）溶液中结晶，该溶液含有各种少量的metacetamol作为添加剂。成核动力学的影响进行了研究，通过测量的诱导时间成核和亚稳区的宽度，使用聚焦光束反射测量（FBRM）和衰减全反射（ATR-UV/维斯）光谱。诱导时间和介稳区宽度均表示为添加剂浓度的函数。发现少量的metacetamol（1-4 mol-%）通过延长诱导时间和亚稳区宽度对成核产生显著抑制。随着metacetamol浓度的增加，观察到对乙酰氨基酚晶体的形态从板状到柱状的逐渐变化。溶剂对扑热息痛晶体的尺寸也有显著影响，因为在IPA中获得的晶体比在水溶液中获得的晶体小。对乙酰氨基酚的溶出速率通过掺入4 mol-%的metacetamol而提高，具有最大的效果。过饱和度控制（SSC）的方法实施的PCM-IPA系统与和没有metacetamol在试图控制和获得更大的metacetamol掺杂的扑热息痛晶体。
Paracetamol (PCM) was crystallized from an isopropanol (IPA) solution containing various small amounts of metacetamol as an additive. The effect on the nucleation kinetics was studied by measuring the induction time to nucleation and the metastable zone width using focused beam reflectance measurements (FBRM) and attenuated total reflectance (ATR-UV/Vis) spectroscopy. Both the induction time and the metastable zone width were expressed as functions of the additive concentration. Small amounts of metacetamol (1–4 mol-%) were found to cause significant inhibition to the nucleation by extending both the induction time and the metastable zone width. A progressive change in the morphology of the paracetamol crystals from tabular to columnar habit was observed with increasing metacetamol concentration. The solvent also had a significant effect on the size of the paracetamol crystals as smaller crystals were obtained in IPA than in aqueous solution. The dissolution rate of paracetamol was improved by the incorporation of metacetamol with 4 mol-% having the most effect. A supersaturation control (SSC) approach was implemented for the PCM-IPA system with and without metacetamol in an attempt to control and obtain larger metacetamol-doped paracetamol crystals.