Solid-liquid equilibrium of paracetamol in water-ethanol and water-propylene glycol mixtures

Abstract

Solubility is one of most important property to produce active pharmaceutical ingredients (APIs), beyond of being related to its bioavailability. In this context, itwas determined paracetamol solid-liquid equilibriumin temperatures from20 to 50 °C for two solvent systems:water - ethanol andwater - propylene glycol (PG), by refractometry method. The experimental results were compared with five thermodynamic models (Apelblat,Wilson, UNIQUAC, NRTL and λh) and data from the literature, showing good correlations for Apelblat and the best predictive fit for the NRTL model in both solvent mixtures. Maximum solubility values were observed in a 75% ethanol composition, this result being unusual and not the same with PG. the results of this work were compared with the literature and some references point to similar behavior. Optical microscopy and X-ray diffractionmeasurements of the solids in equilibrium with the liquid indicate that maximum solubility is not associated with a change in the crystalline structure of the solid