Sheokand Sneha, Modi Sameer R, Bansal Arvind K
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Punjab 160062, India.
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Punjab 160062, India.
Eur J Pharm Biopharm. 2016 May;102:77-86. doi: 10.1016/j.ejpb.2016.03.006. Epub 2016 Mar 3.
A minor amount of amorphous phase, especially present on the surface of crystalline pharmaceutical actives, can have a significant impact on their processing and performance. Despite the presence of sophisticated analytical tools, detection and quantification of low levels of amorphous content pose significant challenges owing to issues of sensitivity, suitability, limit of detection and limit of quantitation. Current study encompasses the quantification of amorphous content in the crystalline form of celecoxib (CLB) using a dynamic vapor sorption (DVS) based method. Water, used as the solvent probe, achieved equilibration within a very short period of time (i.e. 6h) due to hydrophobic nature of CLB, thus allowing development of a rapid quantification method. The study included optimization of instrument and sample related parameters for the development of an analytical method. The calibration curve for amorphous CLB in crystalline CLB was prepared in the concentration range of 0-10% w/w. The analytical method was validated for linearity, range, accuracy and precision. The method for quantification was found to be linear with R(2) value of 0.999, rapid and sensitive for quantification of low levels of amorphous CLB content. It was able to detect the presence of amorphous phase in a predominantly crystalline phase at concentrations as low as 0.3% w/w. The limit of quantitation was found to be 0.9% w/w. Moreover, the influence of mechanical processing on the amorphous content in crystalline CLB was also investigated.
少量的非晶相，尤其是存在于结晶药物活性成分表面的非晶相，会对其加工过程和性能产生重大影响。尽管有先进的分析工具，但由于灵敏度、适用性、检测限和定量限等问题，低水平非晶含量的检测和定量仍面临重大挑战。当前的研究包括使用基于动态蒸汽吸附（DVS）的方法对塞来昔布（CLB）结晶形式中的非晶含量进行定量。由于CLB的疏水性，用作溶剂探针的水在很短的时间内（即6小时）就达到了平衡，从而得以开发一种快速定量方法。该研究包括为开发分析方法而对仪器和样品相关参数进行优化。在0-10% w/w的浓度范围内制备了结晶CLB中非晶CLB的校准曲线。对该分析方法的线性、范围、准确性和精密度进行了验证。发现该定量方法具有线性，R(2)值为0.999，对于低水平非晶CLB含量的定量快速且灵敏。它能够检测到在主要为结晶相的相中低至0.3% w/w浓度的非晶相的存在。定量限为0.9% w/w。此外，还研究了机械加工对结晶CLB中非晶含量的影响。
