Mirza Sabiruddin, Miroshnyk Inna, Heinämäki Jyrki, Antikainen Osmo, Rantanen Jukka, Vuorela Pia, Vuorela Heikki, Yliruusi Jouko
Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
AAPS PharmSciTech. 2009;10(1):113-9. doi: 10.1208/s12249-009-9187-4. Epub 2009 Jan 30.
Crystal morphology engineering of a macrolide antibiotic, erythromycin A dihydrate, was investigated as a tool for tailoring tabletting performance of pharmaceutical solids. Crystal habit modification was induced by using a common pharmaceutical excipient, hydroxypropyl cellulose, as an additive during crystallization from solution. Observed morphology of the crystals was compared with the predicted Bravais-Friedel-Donnay-Harker morphology. An analysis of the molecular arrangements along the three dominant crystal faces [(002), (011), and (101)] was carried out using molecular simulation and thus the nature of the host-additive interactions was deduced. The crystals with modified habit showed improved compaction properties as compared with those of unmodified crystals. Overall, the results of this study proved that crystal morphology engineering is a valuable tool for enhancing tabletting properties of active pharmaceutical ingredients and thus of utmost practical value.
研究了大环内酯类抗生素二水合红霉素A的晶体形态工程，将其作为一种调整药物固体压片性能的工具。在从溶液中结晶过程中，通过使用一种常见的药用辅料羟丙基纤维素作为添加剂来诱导晶体习性改变。将观察到的晶体形态与预测的布拉维-弗里德尔-多纳伊-哈克形态进行比较。利用分子模拟对沿三个主要晶面[(002)、(011)和(101)]的分子排列进行了分析，从而推断出主体-添加剂相互作用的性质。与未改性晶体相比，习性改性的晶体表现出改善的压实性能。总体而言，本研究结果证明晶体形态工程是增强活性药物成分压片性能的一种有价值的工具，因此具有极大的实用价值。
