Jain Tanshu, Sheokand Sneha, Modi Sameer R, Ugale Bharat, Yadav Ram Naresh, Kumar Navin, Nagaraja C M, Bansal Arvind K
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S. A. S Nagar, Mohali, Punjab, India.
Department of Chemistry, Indian Institute of Technology (IIT), Ropar, Punjab, India.
Eur J Pharm Sci. 2017 Mar 1;99:318-327. doi: 10.1016/j.ejps.2016.12.034. Epub 2017 Jan 3.
Differential surface anisotropy of different crystals of the same API can have a significant impact on their pharmaceutical performance. The present work investigated the impact of differential surface anisotropy of two plate-shaped crystals of aspirin (form I) on their hygroscopicity, stability and compaction behavior. These crystals differed in their predominant facets (100) and (001) and were coded as AE-100 & E-001. (100) facets exposed polar carbonyl groups which provided hydrophilicity to the facets. In contrast, (001) facets possessed hydrophobicity as they exposed non-polar aryl and methyl groups. Both the samples showed different degradation behavior, at various stability conditions (i.e. 40°C/75%RH, 30°C/90%RH and 30°C/60%RH) and different time intervals. Polar groups of aspirin have been reported to be prone to hydrolysis due to which AE-100 was less stable than E-001. Dynamic vapor sorption (DVS) analysis at different simulated stability conditions also supported this observation, wherein AE-100 showed higher moisture sorption than E-001. Both the samples having similar particle size, shape, surface area and hardness value, showed differences in their compactibility. However, milling narrowed down the predominance of facets and both the milled samples showed similar stability and compaction behavior. This study was also supported by surface free energy determination, molecular modeling and face indexation of unmilled and milled samples.
同一活性药物成分（API）的不同晶体的表面各向异性差异会对其药学性能产生重大影响。本研究调查了阿司匹林（晶型I）的两种片状晶体的表面各向异性差异对其吸湿性、稳定性和压片行为的影响。这些晶体的主要晶面（100）和（001）不同，分别编码为AE - 100和E - 001。暴露极性羰基的（100）晶面使晶面具有亲水性。相比之下，暴露非极性芳基和甲基的（001）晶面具有疏水性。在不同的稳定性条件（即40°C/75%相对湿度、30°C/90%相对湿度和30°C/60%相对湿度）及不同时间间隔下，两个样品均表现出不同的降解行为。据报道，阿司匹林的极性基团易于水解，因此AE - 100比E - 001稳定性差。在不同模拟稳定性条件下的动态水蒸气吸附（DVS）分析也支持了这一观察结果，其中AE - 100的吸湿量高于E - 001。两个样品的粒径、形状、表面积和硬度值相似，但压片性能存在差异。然而，研磨减小了晶面的优势程度，两个研磨后的样品表现出相似的稳定性和压片行为。未研磨和研磨后样品的表面自由能测定、分子模拟和晶面指数分析也支持了本研究。
