Calculation and interpretation of activation energies for the desolvation of cloxacillin, dicloxacillin and nafcillin monohydrate in the solid-state

The purpose of this research was to characterize and interpret the desolvation kinetics of a series of penicillin derivative in monohydrates using nonisothermal gravimetric analysis. These results were compared to isothermal gravimetric studies and further interpreted by examining the rehydration of the compounds using a series of moisture adsorption isotherms as well as computer simulated molecular dynamics. Nonisothermal and isothermal studies were conducted using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). To calculate the kinetic parameters and select a model for the reaction mechanism the data were fit to various appropriate mathematical models using linear as well as nonlinear curve fitting. The isothermal results for desolvation were consistent with previous studies in that use of all mechanistic models resulted in similar calculated activation energies and correlation coefficients. There was a small difference in the activation energies calculated by linear regression and by nonlinear regression, however the activation energies and correlation coefficients were still similar for each reaction mechanism within the specific regression model used. Both the linear and nonlinear regression methods for the nonisothermal studies gave similar results. A large variation in the activation energy was found for data fit to the various mechanisms, although no single mechanistic model fit the data the best, the nonisothermal methods did suggest that a diffusion model was more likely than the others. It is likely that the computed desolvation activation energy is the sum of several processes and not a single reaction mechanism. The rehydration studies used to further interpret these activation energies seem to indicate that the mechanism for desolvation upon heating is different than that for desolvation under a vacuum. This finding was further studied with the aid of computer simulated molecular dynamics.