IN-SITU OPTICAL INTERFEROMETRIC STUDIES OF THE GROWTH AND DISSOLUTIONBEHAVIOR OF PARACETAMOL (ACETAMINOPHEN) .1. GROWTH-KINETICS

Paracetamol (acetaminophen, 4-hydroxyacetanilide) is a typical represe ntative of over-the-counter analgesic and antipyretic drugs which are commonly administered as tablets. For these materials, crystallization from solution is an important stage of pharmaceutical production whic h defines many physicochemical properties of the solid dosage forms. T he approach developed in this work involves investigation of the surfa ce growth kinetics of single paracetamol crystals using in situ laser interferometry. All the major crystal faces of paracetamol (e.g. {110} , {001} and <{20(1)over bar }>) have shown a dislocation growth mechan ism. The structure and the effective Burgers vector of the dislocation s have been obtained and the specific step free energy, alpha, and the step kinetic coefficient, beta, determined. The dissolution behavior of paracetamol crystals is affected by dislocation core instability an d, to a lesser extent, by stress in the uppermost crystal layer for wh ich the critical undersaturations have been determined. The step veloc ity is a nonlinear function of supersaturation. This nonlinearity is p articularly important for the {110} crystal faces and results in the f ormation of large macrosteps, growth hysteresis, and overall kinetic i nstability. The crystal defects are mostly concentrated in the {110} g rowth sectors which therefore define the overall crystal quality. Anal ysis of the paracetamol crystal structure, surface energies, and the s urface-solvent interactions suggests that specific hydrogen bonding pl ays a major role in defining the surface kinetics and, consequently, t he crystal shape and crystal quality.