Quantification of low levels of amorphous content in crystalline celecoxib using dynamic vapor sorption (DVS)

Abstract

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 R2 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.