Inclusion complex formation of acetaminophen by heating and cogrinding with cyclodextrins

Abstract

The effects of heating or grinding processes on the formation of the inclusion complex between acetaminophen andα- orβ-cyclodextrin were investigated. The interaction of excess amounts of acetaminophen with acetaminophen-cyclodextrin systems was also examined. It was found that the process of grinding or freeze-drying did not cause any interaction between acetaminophen andα-cyclodextrin, but heating could result in its complex formation. However, all the processes (heating, freeze-drying and grinding), could improve the inclusion formation of acetaminophen andβ-cyclodextrin. An excess of acetaminophen could easily interact with the inclusion complex of acetaminophen andβ-cyclodextrin to result in an exothermic peak at 160°C in DSC thermograms. Consecutive endothermic and exothermic peaks around 150–160°C appeared in the DSC thermograrns of acetaminophen-β-CD systems, but not in the DSC curves of acetaminophen-α-CD systems. This consecutive transition phenomenon might be due to the fusion of the amorphous state of excessive acetaminophen caused by grinding and the molecular interaction that occurred between an excess of fused acetaminophen and the inclusion complex