Drug-excipient compatibility studies in binary and ternary mixtures by physico-chemical techniques

This work is part of a systematic study undertaken to find and optimize a general method of detecting the drug-excipient interactions, with the aim of predicting rapidly and inexpensively the long term stability of a pharmaceutical product and speed up its marketing. Here, in particular, the compatibility of haloperidol with several excipients (PVP, magnesium stearate and α-lactose) in binary and ternary mixtures, both as prepared and ball-milled, has been assessed by thermal methods, electron microscopy, IR spectroscopy and X-ray diffraction. The differences between the experimental behaviour of the systems and that expected as weighted average of similarly treated pure components are interaction indicators. The DSC has proven to be, among the selected analytical techniques, the most sensitive and specific in assessing the compatibility. A strong interaction has been observed between PVP and haloperidol. It is favoured by the mechanical stress and is more evident in the composition 20:80. On the contrary, α-lactose and magnesium stearate were found to be compatible with the drug.