Molecular mobility of the paracetamol amorphous form

The purpose of this paper is to study the molecular mobility of paracetamol molecules in their amorphous state below the glass transition temperature (T(g)) in order to evaluate the thermodynamic driving force which allows the amorphous form to recrystallize under different polymorphic modifications. Samples were aged at temperatures of -15, 0, 6, and 12°C for periods of time from 1 h to a maximum of 360 h. The extent of physical aging was measured by a DSC study of enthalpy recovery in the glass transition region. The onset temperature of glass transition was also determined (T(g)). Enthalpy recovery (ΔH) and change in heat capacity (ΔCp) were used to calculate the mean molecular relaxation time constant (τ) using the empirical Kohlausch-Williams-Watts (KWW) equation. Enthalpy recovery and onset glass transition temperature increased gradually with aging and aging temperatures. Structural equilibrium was reached experimentally only at an aging temperature of 12°C (T(g)-10°C), according to the ΔH∞ results. The experimental model used is appropriate only at lower aging temperatures, while at higher ones the complexity of the system increases and molecular polymorphic arrangement could be involved. When structural equilibrium is experimentally reached, molecules can be arranged in their lowest energy state, and the polymorphic form I formation is the one preferred.