Crystallization Kinetics of Ultraviscous Acetaminophen by Heat Capacity and Enthalpy Measurements and Diffusion Control

Abstract

Crystallization kinetics of ultraviscous acetaminophen has been studied at 308.2, 318.2, and 328.2 K by measuring the heat capacity, C(p), and the heat release in real time up to a period of 2.5 days. C(p) decreases according to an inverted sigmoid-shape curve, and the heat released increases according to a similar shape. The extent of crystallization determined from the two measurements differs, thus indicating that the interfacial liquid's C(p) may be slightly different from that of the bulk liquid. Both the excess C(p) of the liquid over the crystal phase and the corresponding excess enthalpy decrease with decrease in the temperature. The kinetics of crystallization follows the Kolmogorov-Johnson-Mehl-Avrami relation, alpha(cryst)(t) = 1 - exp(-kt(m)). The logarithm of the rate constant, ln k, increases from -40.78 at 308.2 K to -32.85 at 328.2 K, and m from 3.60 to 3.83. The product of k and the calorimetric relaxation time remains constant with changing temperature thus showing that the two are inversely related. This shows that crystallization may be diffusion-controlled in the ultraviscous melt. The C(p) data indicate that slow crystallization of melt produces acetaminophen's (monoclinic) form I. Several effects usually overlooked in the crystallized kinetics formalisms have been described.