Influence of environment on piroxicam polymorphism: Vibrational spectroscopic study

FTIR and FT-Raman spectroscopies were used to evaluate the mechanism of tra nsformation of piroxicam into its different forms (alpha, beta, and monohyd rate), depending on the environment. These vibrational techniques allowed u s to identify the forms of piroxicam that crystallize from different solven ts at different cooling rates and the conformation of the drug in some of i ts derivatives: piroxicam hydrochloride, piroxicam thallium and sodium salt hemihydrates, and piroxicam sodium salt. The usefulness of Raman spectrosc opy in characterizing piroxicam:beta -cyclodextrin (P beta CD) inclusion co mpounds was described. The Raman spectrum of 1.2 P beta CD was discussed in comparison with that of the corresponding piroxicam sodium salt containing inclusion compound (1:2 PNa beta CD) in order to study the influence of th e piroxicam derivative used on the structure of the inclusion compound. The Raman results showed that in both of the inclusion compounds the piroxicam mainly assumes the zwitterionic structure typical of a monohydrate; theref ore, the kind of derivative used does not affect the conformation of the dr ug in its inclusion compound. The effect of the method of synthesis utilize d (freeze-drying or freeze-thaw cycling) to obtain 1:2.5 P beta CD was inve stigated. The inclusion compound obtained by freeze-thaw cycling proved to be more crystalline and to contain a higher amount of the beta form than th e freeze-dried inclusion compound. Raman spectroscopy proved to be a useful technique for evaluating the effectiveness of the manufacturing process in relation to the pharmaceutical properties of the drug and to the nondestru ctive and noninvasive on-line quality control of the industrial. products. (C) 2000 John Wiley & Sons, Inc.