通过结晶水改善对羟基苯甲酸的压片性能：分子层面的见解
Improved tableting properties of p-hydroxybenzoic acid by water of crystallization: a molecular insight.
作者信息
Sun Changquan, Grant David J W
机构信息
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Weaver-Densford Hall, 308 Harvard Street S.E., Minneapolis, MN 55455-0343, USA.
出版信息
Pharm Res. 2004 Feb;21(2):382-6. doi: 10.1023/b:pham.0000016272.81390.b4.
PURPOSE
To understand the influence of water in the crystal structure on the compaction properties of otherwise structurally similar crystals, p-hydroxybenzoic acid anhydrate (HA) and the monohydrate (HM) were used as model compounds.
METHODS
Bulk powder of HM was prepared by exposing HA powder to 97% relative humidity at 23 degrees C. Each powder, HA or HM, was uniaxially compressed and triaxially decompressed under various pressures to form square-faced tablets. The tensile strength and porosity of the tablets were measured.
RESULTS
Incorporation of water into the crystal lattice results in greater tablet strength and larger reduction in volume for HM crystals than for HA crystals. Both HA and HM crystals contain hydrogen-bonded, zigzag-shaped layers that lie parallel to the (401) plane. When HA crystals are compressed, the zigzag-shaped layers mechanically interlock, inhibiting slip and reducing plasticity. However, water molecules in the HM crystals assume a space-filling role, which increases the separation of the layers. This effect allows easier slip between layers and provides greater plasticity of HM crystals, which increases the interparticulate bonding area under the same compaction pressure. However, the water molecules in the HM crystals increase their lattice energy by forming a three-dimensional hydrogen-bonding network. The greater bonding strength that results is reflected in greater tensile strength of HM compacts at zero porosity.
CONCLUSIONS
The presence of water molecules in the crystal structure of p-hydroxybenzoic acid facilitates plastic deformation of HM crystals, thereby enhancing their bonding strength and giving much stronger tablets than of HA crystals.
目的
为了解晶体结构中的水对其他结构相似晶体压实性能的影响，选用对羟基苯甲酸无水物（HA）和一水合物（HM）作为模型化合物。
方法
通过将HA粉末在23℃下暴露于相对湿度97%的环境中制备HM的散装粉末。将每种粉末，即HA或HM，在不同压力下进行单轴压缩和三轴解压以形成方形片剂。测量片剂的抗张强度和孔隙率。
结果
与HA晶体相比，HM晶体中晶格结合水会使片剂强度更高，体积减小更大。HA和HM晶体均含有平行于（401）平面的氢键连接的锯齿形层。当HA晶体被压缩时，锯齿形层机械互锁，抑制滑移并降低可塑性。然而，HM晶体中的水分子起到填充空间的作用，这增加了层间距。这种效应使层间更容易滑移，并使HM晶体具有更大的可塑性，从而在相同压实压力下增加颗粒间的结合面积。然而，HM晶体中的水分子通过形成三维氢键网络增加了其晶格能。由此产生的更大结合强度体现在孔隙率为零时HM压片的更高抗张强度上。
结论
对羟基苯甲酸晶体结构中水分子的存在促进了HM晶体的塑性变形，从而增强了它们的结合强度，使片剂比HA晶体更强。
Zotero 插件