Adsorption of water by anhydrous nedocromil sodium from 20 to 40 °C

Abstract

Three different powder preparations of the drug disodium 9-ethyl-4, 6-dioxo-10-propyl-4H,6H pyrano[3,2-g]quinoline-2,8-dicarboxylic trihydrate, Nedocromil sodium (trade name Tilade), have been fully dehydrated in a vacuum and their water vapor adsorption characteristics quantitatively assessed at different water vapor pressures over a temperature range 20 to 40 degrees C. At saturated vapor pressures, 100% RH, rates of adsorption are around 0.1 s(-1/2). Graphs of square root of time against reduced mass during uptake of water vapor at vapor pressures in the range 20 to 47 mm of Hg, all equivalent to 100% RH, indicate control by a diffusion mechanism with activation energies in the range 8 to 24 kJ mol(-1), dependent on the powder preparation method. In two of the powders nonlinear Arrhenius-type plots are interpreted as showing that control of the process is dependent on the surface's ability to hold water molecules at the experimental temperature. The variation in activation energies and the calculated values for diffusivities, around 1 x 10(-13) m(2) s(-1), are used to explore structural involvement in the overall water adsorption process. The measured values of water vapor diffusivity into the structure have been used to predict the water solubility of nedocromil sodium trihydrate, and the results show good agreement to reported solubilities. This approach tosolubility prediction is an alternative to the Noyes and Whitney method where ions leaving the surface are monitored.

The Change of the Rate‐Controlling Processes with Temperature in the Hydration of Anhydrous Nedocromil Sodium by Water Vapor

“…The data was collected by Richards et al 4 mostly as time versus mass loss, for which Figure 3 is a typical example. To use the analysis leading to eq 24, rates at specified times must be taken from Figure 3 by drawing tangents to the curve at these times, such as points X and Y.…”

“…Given the data summarized in Richards et al, 4 it is not possible to sensibly extract the direct effect of temperature and pressure on the reaction rate. For example, when the water vapor pressure was maintained at 18.7 mmHg, a plot of logarithm temperature versus logarithm reaction rate (Figure 5) does not allow any correlation with the theoretical predictions from eq 6 of a line of slope of either −1/2 or −5/2 because of the difficulty encountered in interpreting experimental data when the water vapor pressure is not close to the saturated value at a given temperature.…”

“…From the results presented in the previous paper, 4 it was shown that more than one process is occurring at any time. Also, as the temperature increases, the rate-controlling process changes.…”

“…This linearity was taken to indicate a diffusion mechanism, and activation energies in the range 8-24 kJ mol −1 were found. 4 The activation energy values appeared to be dependent on the preparation method of the sample being studied. The data were used to obtain the diffusivity of water mol-ecules into the crystal, and the measured values for diffusivities (∼1 × 10 −13 m 2 s −1 ) were taken to imply a significant crystal structure involvement in the overall water sorption process.…”

Solvation Mechanisms of Nedocromil Sodium From Activation Energy and Reaction Enthalpy Measurements of Dehydration and Dealcoholation

“…Isothermal reaction rate data obtained thermogravimetrically for the hydration of nedocromil sodium (NS; di‐sodium 9‐ethyl‐4,6‐dioxo‐10‐propyl‐4H,6H pyranol[3,2‐g]quinoline‐2,8‐dicarboxylic) trihydrate; trade name, Tilade) was analyzed theoretically in our earlier publications on this system 1,2. A dominant role for the nucleation process of the hydrate phases in this system was inferred but was not researched at the time.…”