By. Shekunov et Djw. Grant, IN-SITU OPTICAL INTERFEROMETRIC STUDIES OF THE GROWTH AND DISSOLUTIONBEHAVIOR OF PARACETAMOL (ACETAMINOPHEN) .1. GROWTH-KINETICS, JOURNAL OF PHYSICAL CHEMISTRY B, 101(20), 1997, pp. 3973-3979
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.