Drug excipient compatibility studies by physico-chemical techniques: the case of atenolol

We apply a range of techniques (thermal methods, microscopy, X-ray diffraction, IR spectroscopy) to characterize a drug (atenolol), several excipients (PVP=polyvinylpyrrolidone, MGST=magnesium stearate, Avicel©) and drug- excipients mixtures either as prepared, annealed, and exposed to moisture. We compare the data of the mixtures with those computed from a weighted average of similarly treated pure compounds to find evidence of drug properties modified by the interaction with the excipient. We find that thermal response is by far the most sensitive indicator of interaction while IR is the least sensitive one. Avicel© has essentially no interaction with atenolol, while MGST modifies significantly only the thermal response of the drug in the MGST-rich mixtures. PVP interacts strongly with atenolol, and this interaction appears to be mediated by the substantial amount of hydration water the excipient brings in its mixtures with a water-free drug.