Banga Sheere, Chawla Garima, Varandani Deepak, Mehta B R, Bansal Arvind K
Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Punjab - 160 062, India.
J Pharm Pharmacol. 2007 Jan;59(1):29-39. doi: 10.1211/jpp.59.1.0005.
Crystallization is often used in the pharmaceutical industry for purification and isolation of drugs, and also as a means of generating polymorphs or isomorphs. The aim of this study was to investigate the role of extrinsic crystallization parameters on the crystallized product, with special emphasis on improving the mechanical properties of acicular celecoxib. Celecoxib isomorphs were prepared using different techniques (solvent crystallization and vapour diffusion) and crystallization conditions (solvents, stirring, degree of supersaturation, crystallization temperature and seeding). Powder X-ray diffractometry, spectroscopic and thermal methods were used to investigate physical characteristics of crystals. Growth kinetics and aggregation dynamics of crystallization in polar and non-polar solvents were simulated using a dynamic light scattering method. The quick appearance of broad peaks over the range of 10-8000 nm in chloroform during crystallization simulation studies indicated faster aggregation in non-polar solvents. Aspect ratio, flow, compressibility and surface area of recrystallized products were also determined. Surface topography was determined by atomic force microscopy and the lath-shaped crystals (aspect ratio of 2-4) exhibited a roughness index of 1.79 in comparison with 2.92 for needles. Overall, the lath-shaped isomorphs exhibited improved flow and better compressibility.
结晶在制药工业中常用于药物的纯化和分离，也是生成多晶型物或同晶型物的一种手段。本研究的目的是研究外在结晶参数对结晶产物的作用，特别着重于改善针状塞来昔布的机械性能。采用不同技术（溶剂结晶和气相扩散）和结晶条件（溶剂、搅拌、过饱和度、结晶温度和晶种）制备了塞来昔布同晶型物。使用粉末X射线衍射法、光谱法和热分析法研究晶体的物理特性。采用动态光散射法模拟了极性和非极性溶剂中结晶的生长动力学和聚集动力学。在结晶模拟研究中，氯仿中10 - 8000 nm范围内宽峰的快速出现表明非极性溶剂中聚集更快。还测定了重结晶产物的长径比、流动性、可压缩性和表面积。通过原子力显微镜测定表面形貌，板条状晶体（长径比为2 - 4）的粗糙度指数为1.79，而针状晶体为第二点九二。总体而言，板条状同晶型物表现出改善的流动性和更好的可压缩性。
