Effect of surface modification on hydration kinetics of carbamazepine anhydrate using isothermal microcalorimetry

Abstract

ABSTRACTeach temperature. The activation energy (E) of nuclei formation and crystal growth process for hydration of surface-modified CBZ anhydrate were evaluated to be 20.1 and 32.5 kJ/mol, respectively, from Arrhenius plots, but the Es of intact anhydrate were 56.3 and 26.8 kJ/mol, respectively. The dissolution profiles showed that the surface-modified sample dissolved faster than the intact sample at the initial stage. The dissolution kinetics were analyzed based on the Hixon-Crowell equation, and the dissolution rate constants for intact and surface-modified anhydrates were found to be 0.0102 ± 0.008 mg 1/3 min -1 and 0.1442 ± 0.0482 mg 1/3 ·min -1 . The surface-modified anhydrate powders were more stable than the nonmodified samples under high humidity and showed resistance against moisture. However, surface modification induced rapid dissolution in water compared to the control.The purpose of this research was to improve the stability of carbamazepine (CBZ) bulk powder under high humidity by surface modification. The surfacemodified anhydrates of CBZ were obtained in a specially designed surface modification apparatus at 60°C via the adsorption of n-butanol, and powder xray diffraction, Fourier-Transformed Infrared spectra, and differential scanning calorimetry were used to determine the crystalline characteristics of the samples. The hydration process of intact and surfacemodified CBZ anhydrate at 97% relative humidity (RH) and 40 ± 1°C was automatically monitored by using isothermal microcalorimetry (IMC). The dissolution test for surface-modified samples (20 mg) was performed in 900 mL of distilled water at 37 ± 0.5°C with stirring by a paddle at 100 rpm as in the Japanese Pharmacopoeia XIII. The heat flow profiles of hydration of intact and surface-modified CBZ anhydrates at 97% RH by using IMC profiles showed a maximum peak at around 10 hours and 45 hours after 0 and 10 hours of induction, respectively. The result indicated that hydration of CBZ anhydrate was completely inhibited at the initial stage by surface modification of n-butanol and thereafter transformed into dihydrate. The hydration of surface-modified samples followed a 2-dimensional phase boundary process with an induction period (IP). The IP of intact and surface-modified samples decreased with increase of the reaction temperature, and the hydration rate constant (k) increased with increase of the temperature. The crystal growth rate constants of nuclei of the intact sample were significantly larger than the surface-modified sample's at

Characterizing the conversion kinetics of carbamazepine polymorphs to the dihydrate in aqueous suspension using Raman spectroscopy

“…Other possible kinetic models based on solid-state reaction mechanisms were also considered [51][52][53] (Table 3).…”

Insightful vibrational imaging study on the hydration mechanism of carbamazepine

“…According to the US Food and Drug Administration (FDA) report, commercial tablets of anhydrous CBZ (CBZ III) change into its dihydrate form within two weeks at 40 1C, under an atmosphere of 97% RH, decreasing the in vitro dissolution rate of the API. 37 The spatial distribution and stability of pure anhydrous CBZ tablets in different humidity conditions was monitored by Raman imaging applied to CBZ III tablets stored at 6, 60 and 89% RH, over 168 hours (one week) at 20-22 1C (Fig. 5).…”

Pharmaceutical solvates, hydrates and amorphous forms: A special emphasis on cocrystals

“…For example, stable and metastable carbamazepine can transform to the dihydrate form when exposed to water vapor at 37°C [15]. The dihydrate of carbamazepine can also be generated by cooling crystallization from a saturated ethanol solution [16]. The stable anhydrous form I of carbamazepine showed a marked improvement in dose-dependent bioavailability (both C max and AUC) compared to the dihydrate form [17].…”