A STUDY OF THE CHANGES DURING HEATING OF PARACETAMOL

The orthorhombic form of paracetamol has been shown to exhibit greater compressibility and faster dissolution than the monoclinic form. The orthorhombic form is produced by melting of monoclinic crystals of par acetamol followed by cooling at specific rates. Cooling rate, although a very important factor, is not the only factor influencing the forma tion of either of the two morphs. To study the cooling rate required f or production of form II, paracetamol samples were melted in a differe ntial scanning calorimeter, cooled at three specific rates, and melted again. In all of the samples, cooling resulted in the glassy form fol lowed by recrystallization and the melting of form II. On the hot-stag e microscope both forms were produced in one sample. Standardizing con ditions for prediction of the resulting form remains a problem. There seems to be a great deal of overlap of the two forms' transition phase s, which would make it difficult to force the crystallization of one f orm by keeping the solution or melt at a specific temperature. The the rmal behavior of paracetamol during the heating and cooling phases mus t be understood in order to manipulate the process. A video camera mou nted on a hot-stage microscope was used to follow the changes during h eating and cooling of both forms. Nucleation, crystal growth, habit tr ansformation, sublimation, and the final melt are shown on snap shots taken from the video.