John P. Elder

A computer program system for kinetic analysis of non-isothermal thermogravimetric data: II. Generalized kinetic analysis and application to coal pyrolysis

Abstract A FORTRAN program is presented which enables the kinetic analysis of extent and rate of reaction data resulting from transposed experimental TG/DTG data obtained under non-isothermal conditions. This software allows one to perform Arrhenius, Friedman and Kissinger analyses for up to nine different solid-state rate-controlling reactions, including n th order, Avrami-Erofeev, phase boundary movement and diffusional models. Data from an investigation of the pyrolysis of a bituminous coal serve as an example of the application of the program.

Thermophysical characterization studies of pharmaceutical hydrates

Abstract The use of both differential scanning calorimetry and thermogravimetry to study the solid state dehydration of hydrated pharmaceutical compounds, and the subsequent behavior of the anhydrous drug is discussed. Three compounds, each with differing thermal behavior serve as examples. Emphasis is placed on applying current solid state reaction kinetics theory to analyze non-isothermal data and ascribe possible mechanisms for the various physicochemical transformations and physical transitions monitored. Solvent removal from a final product can effect partial or total dehydration. It is necessary to ascertain the dehydration temperature limits, and, of equal importance to examine the ability of the compound to rehydrate. The dehydration/rehydration behavior of a drug candidate is described as a practical demonstration of the utility of thermal analysis in pharmaceutical process development.

Reconciliation of Arrhenius and iso-conversional analysis kinetics parameters of non-isothermal data☆

Calculations pertaining to nth order analyses of various solid state reaction kinetics models have been extended to consider iso-conversional Arrhenius (i.e. Friedman) analyses. Non-isothermal extent and rate of reaction data for several models, with the same kinetics parameters, generated over a wide heating rate range, are subjected to both Arrhenius and Friedman nth order analyses over the entire extent of reaction range. A necessary model correction for the Friedman preexponential factors is presented and discussed. Calculated extent of reaction as a function of temperature data at a desired heating rate is compared with the original model data and analogous data generated using the single heating rate Arrhenius analyses parameters. Essentially complete agreement is obtained despite the widely disparate values of the Arrhenius and Friedman derived kinetics parameters. Application of this procedure to the analysis of experimental data is discussed.

The general utility of the nth order model in solid state reaction kinetics

Abstract Computerized kinetics analysis of simulated solid state reaction data has been used to demonstrate how the empirical nth order model may be employed as a diagnostic tool in thermoanalytical research. The characteristic shape of the curves of the extent and rate of reaction as a function of temperature, generated under non-isothermal conditions, together with the magnitude of the kinetics parameters when this data is subjected to nth order Arrhenius analysis, can be utilized to postulate a solid state reaction mechanism, and to calculate the pertinent activation energy and pre-exponential factor. This approach has been employed to analyze the non-isothermal thermogravimetric data characterizing the three stages in the thermal degradation of calcium oxalate monohydrate, postulated to conform to the D4, R3 and D4 mechanisms, respectively. Although the second stage appears to be essentially a single contracting-volume-controlled reaction, the variation of the activation energies and pre-exponential factors with heating rate for the first and third stages implies multiple diffusion-controlled reactions. The procedure has also been used to generate the kinetics parameters of the crystallization of an amorphous form of a candidate drug compound (A2 mechanism) from non-isothermally monitored differential scanning calorimetric data.

A computer program system for kinetic analysis of non-isothermal thermogravimetric data: I. Data acquisition and preparation for kinetic analysis

Abstract FORTRAN software is described which enables the generation of rate of weight change data (DTG) from percentage weight change measurements (TG), obtained under non-isothermal conditions. The program also transposes this information into the dimensionless extent and rate of reaction at unit temperature intervals by means of a cubic spline interpolation. A simple search routine identifies all DTG spikes in the thermogravimetric record, and the temperature and extent of reaction at which the rate attains its maximum value. This total information serves as input data for the kinetic analysis software to be discussed in part II of this communication. An example of the application of this program to the pyrolysis of bituminous coal is presented.

The thermal behavior of lovastatin

Abstract The thermal properties of lovastatin were investigated by DSC aad TG. Melting point and heat of fusion were determined and the thermo-oxidative stability vas studied.

A comment on mathematical expressions used in solid state reaction kinetics studies by thermal analysis

Abstract Computer calculations pertaining to the reaction kinetics analyses of simulated thermoanalytical data, generated under non-isothermal conditions, have been performed. Results obtained by using the two forms of the differential and integral equations descriptive of three different models of rate-controlled solid state reactions: phase boundary movement, nucleation-growth and three-dimensional diffusion, have been examined and compared. Calculations have also been performed to examine the correctness of employing the simple diffusion model equations to analyze data generated by taking into consideration differences in the density of reactant and product. For all models studied and compared, the activation energies are the same, but the pre-exponential factors differ slightly. They can be interconverted by the use of an appropriate multiplicative constant.

The thermal behavior of probenecid tablets. An example of the thermoanalytical complexity encountered in the pharmaceutical Industry

The complexities met in utilizing thermal analysis to describe the physico-chemical behavior of pharmaceutical compounds are demonstrated by discussing that of probenecid tablets. The DSC-TG characteristics (supported when necessary by X-ray diffraction measurements) of the active drug and major excipient components of the formulation are presented and discussed as an example of the information necessary to interpret the thermal behavior of the tabletted drug. Certain expected events are not observed with the tablets, and greater than expected weight losses are encountered. This complicates the interpretation of the thermal response, which is shown to be due to a variety of simultaneous and contiguous events. Loss of absorbed moisture and chemical dehydration, change in physical state, cold crystallization of amorphous material, sublimation, fusion and evaporation all contribute to the overall behavior.

A new accelerated oxidative stability test for glass-forming organic compounds

Abstract A new accelerated thermo-oxidative test has been developed for use with crystalline organic compounds which solidify to a stable vitreous solid from the melt. The principle of the method is based on the fact that the glass transition temperature of the solid is linearly dependent upon the prior oxidative history of the sample. The fixed time, isothermal DSC oxidative stress test is described, and examples of its use with a pharmaceutical compound are given. Results for material which has (a) been subjected to long-term, above-ambient thermo-oxidative ageing, and (b) undergone extended room temperature shelf-life testing, will be presented. The advantages of the procedure over conventional methods will be discussed.