Evaluating the effect of punch-face design on polymorphic transformation mapping after mechanical compaction of chlorpropamide

Abstract

The purpose of this study was to evaluate the effect of different punch-face designs on the polymorphic transformation of chlorpropamide after tablet compaction using comparative results obtained from quantitative powder X-ray diffractometry (Q-PXRD) and Quantitative Raman spectroscopy (Q-Raman). When energy was introduced to chlorpropamide powder Form A, such as heating, compaction forces and dwell time, changes in solid state morphology occurred. Under sufficient pressure and dwell time, Q-PXRD showed that approximately half of Form A overcame the energy barrier and transformed to metastable amorphous form after which it eventually converted to less than 10% of Form C. On the other hand, when Form A was heated prior to compaction, half was converted due to heating. After compaction of the heated Form A with various dwell times, further reduction to less than 20% was observed while Form C increased dramatically beyond 40% with no correlation on punch face designs. Thus, Q-PXRD cannot be used to differentiate the polymorphic interconversion due to punch face designs but can distinguish between the effects of compaction forces and dwell times at ground and excited states. Q-Raman was able to discriminate the polymorphic transition due to compaction forces and dwell times at ground and excited states similar to Q-PXRD. In addition, the technique was most sensitive in detecting the effects of concave and flat-faced punch designs on polymorphic conversion on tablet surfaces. However, indentation was shown not to have significant impact on inducing changes of chlorpropamide polymorphs. Thus, Q-Raman was able to deliver more information on the polymorphic transformation due to punch face designs when compare to conventional Q-PXRD.