Many solid-state reactions and phase transformations performed under isothermal conditions give rise to asymmetric, sigmoidally shaped conversion-time (x-t) profiles. The mathematical treatment of such curves, as well as their physical interpretation, is often challenging. In this work, the functional form of a Maxwell-Boltzmann (M-B) distribution is used to describe the distribution of activation energies for the reagent solids, which, when coupled with an integrated first-order rate expression, yields a novel semiempirical equation that may offer better success in the modeling of solid-state kinetics. In this approach, the Arrhenius equation is used to relate the distribution of activation energies to a corresponding distribution of rate constants for the individual molecules in the reagent solids. This distribution of molecular rate constants is then correlated to the (observable) reaction time in the derivation of the model equation. In addition to providing a versatile treatment for asymmetric, sigmoidal reaction curves, another key advantage of our equation over other models is that the start time of conversion is uniquely defined at t = 0. We demonstrate the ability of our simple, two-parameter equation to successfully model the experimental x-t data for the polymorphic transformation of a pharmaceutical compound under crystallization slurry (i.e., heterogeneous) conditions. Additionally, we use a modification of this equation to model the kinetics of a historically significant, homogeneous solid-state reaction: the thermal decomposition of AgMnO4 crystals. The potential broad applicability of our statistical (i.e., dispersive) kinetic approach makes it a potentially attractive alternative to existing models/approaches.

Introduction and Objective Pulmonary capillary endothelial transient receptor potential vanilloid 4 (TRPV4) channel plays a critical role in mediating the development of cardiogenic pulmonary edema. GSK2798745 is a first-in-class, highly potent, selective, orally active TRPV4 channel blocker being evaluated in a first-time-in-humans study (NCT02119260). Methods GSK2798745 was administered in a randomized, placebo-controlled study design to healthy volunteers in three separate cohorts as single escalating doses, with and without food, and as once-daily repeat doses for up to 14 days, respectively. Two cohorts of subjects with mild to moderate heart failure were also administered GSK2798745 once daily for up to 7 days. Safety, tolerability, and systemic exposure data were collected. Results No significant safety issues or serious adverse events were observed with GSK2798745 in healthy volunteers and patients with heart failure. GSK2798745 systemic exposure data demonstrated linear pharmacokinetics up to 12.5 mg, less than twofold accumulation with once-daily dosing, and a systemic half-life of ~ 13 h. There was a slight increase in GSK2798745 exposure [14% increase in area under the plasma concentration-time curve (AUC) and 9% increase in maximum observed plasma concentration (C max)] after administration with a high-fat meal. Conclusions GSK2798745 was well-tolerated in healthy volunteers and patients with stable heart failure. The safety and exposure data obtained in this study allow further evaluation of the drug in long-term clinical studies in heart failure as well as other indications.

The potential applications of dispersive kinetic models range from solid-state conversions to gas-phase chemical physics and to microbiology. Here, the derivation and application of two such models, for use in solid-state applications, is presented. The models are based on the concept of a Maxwell-Boltzmann distribution of activation energies. The ability of the models to fit/explain an assortment of asymmetric, sigmoidal conversion-versus-time transients presented in the recent literature, as well as to provide physicochemical interpretations of the kinetics via the two fit parameters, alpha and beta, makes them a powerful tool for understanding nucleation/denucleation rate-limited processes that are involved in many phase transformations, dissolutions and crystallizations.

Fundamental kinetic understanding of the formation of various particle size distributions (PSDs) and the time evolution of the mean particle size can guide new synthetic approaches, or improvements to existing ones, for obtaining a desired nanoparticle (NP) morphology, size, and monodispersity. Previous modeling efforts have focused largely on classical kinetic descriptions of nucleation, growth, and particle coarsening/Ostwald ripening (OR) mechanisms, employing numerical methods to simulate the temporal evolution of the NP PSDs. In a very different approach, the activation energy distributions corresponding to recently derived dispersive kinetic models for nucleation and denucleation (Skrdla, P. J. J. Phys. Chem. A 2011, 115, 6413À6425) are utilized in this work to derive analytic functions for the stationary/ steady-state PSDs relevant to each mechanism. Additionally, the same models are used to obtain the time evolution of the mean NP radius. PSDs for these nanometer-scale phase transformation mechanisms have not been predicted previously in the literature using such a direct approach, circumventing the need for stochastic simulation. The predicted PSD shapes, used individually, together, and/or in combination with the known stationary PSD shapes relevant to OR, are used to qualitatively establish the mechanisms giving rise to PSDs reported in the recent literature. Using this approach, the origin of bimodal PSDs and the phenomenon of PSD focusing are explained. Moreover, the time-evolution functions for the mean NP radius predicted by each mechanism are shown to be sufficiently different so as to allow the three mechanisms to be readily distinguished from one another in treating empirical data.

In recent works, the author has shown the utility of new, semiempirical kinetic model equations for treating dispersive chemical processes ranging from slow (minute/hour time scale) solid-state phase transformations to ultrafast (femtosecond) reactions in the gas phase. These two fundamental models (one for homogeneous/deceleratory sigmoidal conversion kinetics and the other for heterogeneous/acceleratory sigmoidal kinetics; isothermal conditions), based on the assumption of a "Maxwell-Boltzmann-like" distribution of molecular activation energies, provide a novel, quantum-based interpretation of the kinetics. As an extension to previous work, it is shown here that the derivation of these dispersive kinetic equations is supported by classical collision theory (i.e., for gas-phase applications). Furthermore, the successful application of the approach to the kinetic modeling of the solid-state decomposition of a binary system, CO2.C2H2, is demonstrated. Finally, the models derived appear to explain some of the (solid-state) kinetic data collected using isoconversional techniques such as those often reported in the thermal analysis literature.