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The evaporative properties of adipic acid, triethanolamine (TEA), and glycolic acid have been studied by thermal analysis. Samples were heated in a simultaneous thermogravimetric–differential thermal analysis (TG–DTA) unit at 10 °C min −1 in a dry nitrogen atmosphere flowing at 100 mL min −1 . Benzoic acid was used to calculate a calibration constant which could then be inserted into a modified Langmuir equation to calculate vapor pressure curves for adipic acid, TEA, and glycolic acid. The results were compared to vapor pressure curves generated by use of Antoine constants, where these were available. Good correlation was obtained between the two sets of curves for adipic acid and TEA. Glycolic acid decomposed and evaporated in the same temperature range, thus, making calculations invalid.

It has been observed that hindered settling experiments usually lead to voluminous data, which is usually characterized as “poorly reproducible”. Many factors might affect these techniques. The ability to control these parameters may result in a better analysis of the outcome and the correct estimation of the particle size. An attempt was made to investigate calcium oxalate monohydrate stability in the presence and absence of cholesterol, while determining the factors which may undermine the results obtained. The data may provide interesting information which may be used in other similar investigations to reduce the negative compacts caused by the low reproducibility. *Posthumously.

A new viscosity–capillary dipometer was designed and used in this investigation. Comparing this piece of equipment with other viscometers, the capillary dipometer is accurate, easy to operate, and much less expensive. The viscosities for calcium hydrogen phosphate and calcium oxalate suspensions are determined using the capillary dipometer. The data shows that this method is suitable for suspensions. This method could also be applied to other liquid dosage forms (i.e., emulsions) to provide quick and accurate results.

The drug acetazolamide (C4H6N4O3S2) was studied using a simultaneous thermogravimetric–differential thermal analysis (TG–DTA) unit. The study covered the temperature range of ambient to 600 °C. The DTA showed a melting point of 258.5 °C followed by a three-stage decomposition. The TG–DTG plots clearly show the decomposition when subjected to heat treatment in a nitrogen atmosphere. A kinetic analysis of all stages was attempted, where a zero-order process appeared to be the best fit mechanism and plots of ln k versus T−1 show this. The values of Eact are shown to vary throughout each stage as the reaction progressed.

This study attempts to identify the degradative process which folic acid undergoes under thermal stress. In order to facilitate the process, the various pieces of the chemical structure, namely, p -amino benzoic acid (PABA), pterin and glutamic acid as both its d - and l -isomers were investigated as separate entities. These structured pieces were then compared to the composite folic acid degradative thermogram in order to identify the peaks seen and provide direction for the interpolation of the degradative mechanism [Thermal stability of folic acid and associated excipients, M.Sc. thesis, 2001]. It was observed that none of the structural pieces could be superimposed as assumed earlier, and hence, an attempt was made to identify the decomposition products using various analytical techniques such as infrared (IR) spectroscopy, mass spectroscopy (MS) and X-ray diffraction (XRD) which suggested that the glutamic acid fragment is lost first as evidenced by acid loss and amide enhancement in the IR spectra. The vitamin was ultimately degraded to carbon fragments and that further identification was not necessary.

There are a number of substances used to calibrate various instruments with benzoic acid being an IUPAC recommended calibration material. It has gained recognition as a reference material because it exhibits an ‘‘ideal’’ behavior. Hence, benzoic acid is often used to aid in determining the enthalpy of sublimation values for various organic substances. In this study, the thermal behavior of benzoic acid is observed from a simultaneous thermogravimetry–differential thermal analysis (TG–DTA) unit. A series of tests under various experimental conditions is performed, and the results allow for the determination of the enthalpy of sublimation values for benzoic acid. The purpose of this study is to investigate the influence of experimental parameters, such as sample preparation procedures, heating rates, atmospheric conditions, and gas flow rates, on the calculated enthalpy of sublimation values. Enthalpy of vaporization for benzoic acid was also calculated. # 2002 Elsevier Science B.V. All rights reserved.

The Langmuir equation was used to construct vapor pressure curves for the sublimation phase of nicotinic acid. Three different approaches were used to calculate the pressure values. In the first, the ‘k’ term of the Langmuir equation was eliminated by comparing the sample with the reference compound, in the second, the actual values of the ‘k’ term were used and in the third approach, the ‘k’ term was kept constant. The vapor pressure curve constructed using the actual values of ‘k’ was in close agreement with the first. This indicates that the ‘k’ term of the Langmuir equation cannot be assumed to be constant and the systematic variation in the values of the ‘k’ term with temperature has to be taken into consideration.

The three naturally occurring available carbonates in northwest Ohio are magnesite, calcite and dolomite. Dolomite is a double carbonate containing calcium and magnesium carbonate in equimolar concentrations. All three carbonates decompose via a single stage process in an atmosphere of nitrogen. The thermal behavior and the kinetics of decomposition were studied using the Arrhenius equation applied to solid-state reactions. It was found that calcite and dolomite supposedly decompose via a zero order mechanism while magnesite decomposes via a first order process. The energy of activation for the decomposition of magnesite, calcite and dolomite were 226.34, 192.50 and 175.05 kJ/mol, respectively. Similarly the ln A-values for magnesite, calcite and dolomite decomposition were 30.70, 20.73 and 18.76, respectively. Finally, the effect of procedural variables on the kinetic parameters of dolomite decomposition was investigated. The three procedural variables studied included flow rate, heating rate and sample size. The kinetic parameters and mechanism remain unaffected by a change in these variables. # 2002 Elsevier Science B.V. All rights reserved.

The thermal behavior of cinnamyl alcohol, which is used in the perfume industry to create a sweet, balsamic and hyacinth-like fragrance, was examined with a simultaneous thermogravimetric–differential thermal analysis (TG–DTA) unit. The sample was subjected to a controlled rising temperature regime under a regulated purge gas flow rate. The evaporation rates and coefficient of evaporation were calculated from TG–DTG data. From the DTG curve, it was found that the evaporation of cinnamyl alcohol is a zero-order process. The activation energy and enthalpy of vaporization for the evaporation process were determined by the use of the Arrhenius and Clausius–Clapeyron equations, respectively. The enthalpy value was calculated to be 68.10±0.84 kJ, while the energy of activation was found to be 66.34±0.84 kJ. The Langmuir equation was applied to the evaporation data, enabling the vapor pressure curves to be determined.

This study aims at providing a simple thermogravimetric method in estimating the vapor pressure characteristics using the Antoine equation as the analytical tool. The heat treatment for the majority of benzoic acid derivatives follows zero order rate processes that are in good correlation with their evaporation process. The optimum conditions for the rising temperature experiments were found when the heating rate was 10 8C/min in an atmosphere of dry nitrogen (100 ml/min). Methyl paraben was taken as the calibration compound since its Antoine constants are reported in literature and its selected thermodynamic parameters were evaluated using the Langmuir equation. The coefficient of vaporization k was determined to be 124525 � 0:8, with units being reported in the SI system. The corresponding vapor pressure plots were obtained for the remaining compounds that followed a zero order evaporation process and their Antoine constants were calculated using the Levenberg‐Marquardt least square curve fit method. # 2002 Elsevier Science B.V. All rights reserved.

Differential scanning calorimetry (DSC) is one of the important thermoanalytical techniques for preformulation studies of pharmaceutical substances. DSC studies can be used to characterize the melting behavior, crystallization, solid–solid transitions and chemical reactions of drugs. The attainment of proper results in a DSC experiment is dependant on a number of factors. The purpose of this study was to establish the appropriate condition for DSC performance. Factorial design and matrix analysis was used extensively in this study. The variables considered in this study were the sample size, heating rates, atmosphere, crucible type and relative humidity (RH). Two model drugs, benzoic acid (typical melting range: 121–123 °C, heat of fusion: 147 J/g) and vanillin (typical melting temperature: 81–83 °C, heat of fusion: 135 J/g) with sample size ranges of 3–5 and 10–12 mg were exposed to heating rates of 2 and 10 °C/min with atmospheres of air and nitrogen. The crucible types evaluated were open crucibles, crimped crucibles without pinhole and crimped crucible with pinhole. The samples were stored under 0, 25, 60 and 100% RH to evaluate the effect of RH on DSC performance. The study in this laboratory established a general protocol for DSC performance, which included the use of a small sample size range (3–5 mg), a low heating rate (2 °C/min), nitrogen as the atmosphere, crimped crucible without pinhole, and storage of the samples in a dry atmosphere (0% RH). Exceptions to the established protocols under various conditions are also discussed.

Thermogravimetric analysis is often used to evaluate the evaporation phenomenon of several substances. The present study was designed to characterize the vaporization characteristics of three essential oils; lemon oil, lavender oil and cinnamon oil and their several components. All three oils represent multi-component systems, whereas their main components represent single component systems. Linalyl acetate was used as the calibration compound and the coefficient of vaporization was obtained as 7×107 (SI system). The order of reaction was first determined for each of the compounds under study. Vapor pressure curves were then plotted using Langmuir and Antoine equations for the compounds, which represent single component systems, undergoing zero-order non-activated evaporation processes. The vapor pressure curves obtained were statistically quantified along with the calculations for the Antoine constants using SPSS version 10.0 software. The energies of activation for cinnamon oil, lemon oil and lavender oil were found to be 45.10, 33.2 and 33.9 kJ/mol, respectively.

The purpose of this study was to identify the degradation products for folic acid which may form under thermal stress. An attempt was made to identify each of the decomposition products using various analytical techniques, such as infrared spectroscopy, mass spectroscopy, and X-ray diffraction, which suggested that the glutamic acid fragment of folic acid is lost first, as evidenced by acid loss and amide enhancement in the IR spectra. The vitamin was ultimately degrading to carbon fragments and further identification was not necessary.

A new titration method proposed by Huyhn et al., which directly measures the interparticular pore volume between the particles in a concentrated suspension, has been further investigated. It is expected that for an ideal powder with uniform spherical particles, the plot of weight versus the void volume should be a straight line passing through the origin. Glass beads, which are nonporous and expected to be ideal, were used in this study and the results were compared with the results of the experiments by Huyhn et al. Glass beads of different size ranges are used to study the effect of particle size on voidage. It was observed that the voidage increases with a decrease in particle size, However, the non-porous glass beads were also found not to be ideal.

Nicotinic acid belongs to the B group of vitamins and is often referred to as Vitamin B3. It is an essential component of a balanced diet and is prescribed as tablet, and in parenteral dosage forms in cases of vitamin deficiency. This study involves a preliminary preformulation study to assess whether nicotinic acid is a good candidate for tablet and capsule manufacture. The manufacturing process for solid dosage forms involves high energy-intensive processes, which mainly include grinding and compaction. The effect of these high-energy processes on the stability of nicotinic acid was evaluated using thermogravimetry (TG) as the primary analytical tool. The initial stage involved characterizing the thermal behavior of the material. It was found that nicotinic acid shows a solid-solid state phase transition, which is reversible. This transition appears as a small endothermic peak on the differential thermal analysis (DTA) curve, just before the dual sublimation-evaporation stage. This was followed by study...

The heat treatment of parahydroxy benzoic acid esters follows zero order rate processes that are in good correlation with their evaporation process. Rising temperature experiments were performed and the optimum conditions were found when the heating rate was 10°C/min in an atmosphere of dry nitrogen, the flow rate of which was maintained at 100 mL/min. The Antoine constants for methyl paraben were substituted into the Antoine equation to get the corresponding vapor pressures that were then used in the Langmuir equation to obtain the value for the coefficient of evaporation k . The Eact value, obtained from the Arrhenius plot, was 75.1 kJ mol−1; the enthalpy of vaporization (ΔHvap) was calculated to be 77.9 kJ mol−1, in very close agreement with the Eact value. Using the Antoine and Langmuir equations, the value of k was experimentally determined to be 124525 ± 0.8, units being in the S.I. system. Taking the value of k to be independent of the substance, the corresponding vapor pressures were obtained for ...

Dolomite decomposes via a 2-stage mechanism in an atmosphere of CO2. The first stage of the decomposition was analyzed in depth using both isothermal and rising temperature kinetics. It was found that the first stage of decomposition follows the Avrami-Erofeev A2 mechanism for the isothermal experiments. However, for the rising temperature experiment, the reaction follows the Avrami-Erofeev A4 mechanism. The energy of activation (Ea) obtained for the isothermal experiments was determined to be 424.97 kJ/mol, while the value for the rising temperature experiment was 647.20 kJ/mol. Similarly, the ln A-value for the isothermal experiments was found to be 49.22, while the ln A-value for the rising temperature experiment was 74.20. The effect of procedural variables on the thermal behavior of dolomite in a nitrogen atmosphere is investigated. The program design variables include alterations in the flow rate, heating rate, grain size, and sample size. Out of these variables, heating rate, flow rate, and grain s...

Captopril is an antihypertensive drug currently being administered in tablet form. The thermal analysis study was carried out using a simultaneous TG–DTA unit. Both the isothermal and non-isothermal experiments are preformed to investigate the thermal degradation process of captopril in its natural state as a solid. The runs were performed in a flowing nitrogen atmosphere. Captopril melted at 106°C followed by decomposition. Based on the order of reaction, one method is used to identify the reaction mechanism in isothermal kinetics and two methods are used to identify the reaction mechanism in non-isothermal kinetics. These methods use the equations established by Avrami–Erofeev, Arrhenius and Freeman and Carroll. However, a kinetic analysis based on the “method of fit” using zero-order, first-order, and second-order equations showed that a first-order process gave a good fit for the Arrhenius plot at certain specific experimental conditions (i.e. very low sample mass). Overall, a second-order process followed by a first-order reaction for the main decomposition process of captopril showed an even better fit for the experiments. The possible reasons for this kinetic behavior are presented. There was up to 2% carbon remaining at 500°C. Thermal analysis was supplemented using Fourier Transform infrared spectroscopy (FTIR), X-ray diffraction and scanning electron microscopy (SEM) methods to identify the captopril with any degradation products which may have formed.

Allopurinol sublimates when subjected to thermogravimetry in a nitrogen atmosphere. The process is zero order and plots of ln k versus reciprocal temperature (K) give a value of 132.64 kJ mol −1 for the activation energy. On the basis that equilibrium is achieved at all temperatures the data is used to establish a plot of the vapor pressure curve versus temperature from which a Clausius–Clapeyron relationship can be used to establish the Δ H for sublimation. The method requires that the equipment is calibrated and data for p -aminobenzoic acid is used for this purpose.

The thermal analysis of basic magnesium carbonate has been investigated by thermogravimetry (TGA), derivative thermogravimetry (DTGA) and differential thermal analysis (DTA). The end product was magnesium oxide formed from the decomposition of magnesium carbonate. The composition of the samples studied varied, but the general formula that represented them was xMgCO3·yMg(OH)2·zH2O. In the present study, the thermal analysis of such magnesium carbonates in nitrogen, carbon dioxide and air was carried out at different heating rates and the origin of the exothermic peak was studied. Generally, the decomposition peaks were endothermic, but a persistent exothermic peak was noted, always accompanied by a very sharp drop in the TG curve, and the weight loss in this region may be significant. The exothermic DTA peak was found to be strongly influenced by the rate at which the samples were heated, sample size and atmospheric conditions.

The evaporation of methyl salicylate is studied using a simultaneous TG–DTA unit. The data are shown to be a zero order rate process. The activation energy calculated from the Kissinger and Ozawa methods as well as from the Arrhenius equations are shown to approximate the latent heat of vaporization calculated from the Clausius–Clapeyron equation. The activation energy values range from 52.5 to 60.4 kJ mol −1 for the Kissinger method, 52.2–63.6 kJ mol −1 for the Ozawa method and 47.2–50.3 kJ mol −1 for the Arrhenius equation.

Extensive studies have been done on the behavior of dolomite when subjected to a rising temperature program. In this study a literature survey was prepared related to the thermal decomposition of dolomite and the probable mechanisms proposed by various workers for the above reaction. Dolomite undergoes a two-stage decomposition in one atmosphere of carbon dioxide; while the same decomposition proceeds via a single step at lower partial pressures of carbon dioxide. The intermediate and final products for the two-stage decomposition of dolomite were isolated and identified using thermogravimetry and X-ray powder diffraction. On each of the isolated samples scanning electron microscopy was carried out. The intermediate products were found to be dolomite, calcite and periclase, while the final products were calcium oxide and periclase. Using these results a mechanism of thermal decomposition for dolomite is proposed.

Grinding is one of the most widely used unit processes in industry. The application of grinding to the pharmaceutical industry is investigated in detail. The process of grinding finds wide application because it leads to surface activation and particle size reduction. This objective is achieved by the application of energy. A lot of the applied energy is dissipated as heat. A number of pharmaceutical solids are known to be heat labile. Thus, the milling operation is a high-energy process, which could lead to detrimental effects on the structural pattern of the material being ground. This could be either due to the heat involved in the milling process or simply because of the high-energy impact of the milling medium. To investigate if grinding had detrimental effects, a detailed study was carried out using dolomite as the material to be ground. The unit cell of dolomite remained intact even after 24 h of grinding in a high-energy vibrating mill. This fact was confirmed using an X-ray powder diffraction methodology. It was found that although grinding did not deform the structural pattern of the dolomitic unit cell, a strain was however introduced in the structure. This strain appeared as a third peak in both the DTG and OTA curves This indicated the possible hazards of prolonged grinding and use of high-energy grinding equipment on the material exposed to the grinding process.

The evaporation of myristic acid [CH 3 (CH 2 ) 12 COOH] was investigated using a simultaneous TG–DTA unit over a temperature range of ambient to 300°C, in a flowing atmosphere of nitrogen at heating rates of 2, 4, 6, 8, 10, 15 and 20°C/min. The flow rates were varied from 50 to 350 ml/min. Kinetic plots for zero-order processes were constructed based on the Arrhenius equation and the Freeman and Carroll method. The activation energy for the evaporation process calculated from two methods was reported. The relationship between the rate of mass loss and the vapor pressure for myristic acid was estimated using the Langmuir and Antoine equations.

The purpose of this study was to find a more efficient method for determining the porosity, or voids, using an insoluble powder in a pharmaceutical suspension. In a random arrangement of uniform spheres the only concern is with the limits of porosity existing within that collection. Theoretically, no equation can completely describe the physical properties of a sediment in a liquid medium without considering its particle size, size distribution, shape features, surface characteristics, etc. For the ideal case dealing with uniform spherical particles, it is expected that the plot of the weight of solid versus the volume of liquid used to fill the voids should be a straight line with zero intercept. A new titration method has been proposed to directly measure the immediate pore volume between particles in the suspension. Further investigation is required to determine its sensitivity such that it may provide a means of differentiating the nature of the particle–particle and particle–liquid attractive forces within a given pharmaceutical suspension system.

Sodium bicarbonate (NaHCO 3 ) is used as an anti-plaque agent in a variety of dental formulations. The aim of this study was to understand the active ingredient–excipient type of interactions in the solid state using thermal analysis. A simple formulation such as a the dental formulation was chosen as an example. Equivalent-ratio w/w binary, tertiary and quaternary mixtures of commercially obtained NaHCO 3 were prepared with solid excipients used in dental formulations. The thermal decomposition of NaHCO 3 was studied in the presence of these excipients, using thermogravimetric analysis (TGA) and differential thermal analysis (DTA). Apart from kinetic analysis, two other methods were developed during the course of this project to assess the solid state reactivity of NaHCO 3 . The reactivity of NaHCO 3 changed in the presence of other solid excipients. The methods developed during this project were successfully used in assessing the solid state reactivity of NaHCO 3 in the presence of other substances. It was concluded that these thermal analysis methods could also be applied to other substances for similar solid state studies.

The purpose of this study is to examine the thermal behavior of saturated fatty acids [CH3(CH2)nCOOH], where n varies from na 10 to na 16, during heating. The studies were performed over a temperature range of ambient temperature to 3508C in a flowing atmosphere of nitrogen, using a SDT 2960 simultaneous TGA‐DTA unit. The acids showed two endotherms due to melting at a lower temperature and vaporization at the higher temperature, which is a zero order process. The influence of flow rate and heating rate on the melting points is reported. The latent heat (DHevap) of vaporization process is calculated by the Antoine equation and the Clausius‐Clapeyron equation at different temperature ranges. The activation energy (Eact) was calculated from the rising temperature experiments, using the Arrhenius equation. These observations should be of use in the characterization of pharmaceutical excipients. # 1999 Elsevier Science B.V. All rights reserved.

The heat treatment of an α-cellulose and a microcrystalline cellulose (Avicel®) in nitrogen gives a one-stage degradation to carbon. This degradation suffers a temperature transposition in the presence of pharmaceutical excipients, namely dibasic calcium phosphate, stearic acid, magnesium stearate, and silicon dioxide. It is possible to produce a kinetic evaluation of these thermal analysis studies in terms of a comparative method by constructing the theoretical TG trace of the binary mixture based on a presumed no-interaction between the two components. There is a variation in behavior to be noted in the different forms of cellulose, and also different values are shown for the Arrhenius parameters. Such variations are also noted in the Avicel® degradation in the presence of other materials. These observations should be of use in the characterization of pharmaceutical excipients. The Arrhenius parameters for α-cellulose degradation using D3 (three-dimensional diffusion) mechanism at the temperature range from 580 to 630 K are 289.32 kJ mol−1 and 1.85×1023 for Eact and A, respectively. The Arrhenius parameters for Avicel® degradation using F1 (first-order) mechanism at the temperature range from 562 to 604 K are 291.35 kJ mol−1 and 1.26×1025 for Eact and A, respectively.

A new approach to establishing kinetic parameters for solid state decompositions is outlined based on the equation of Harcourt and Esson. It enables the integral method to be used without the need to make approximations. It is applied here to a study of certain pharmaceutical excipients used in the formulation of tablets.

The thermal decomposition of ascorbic acid and its excipients in tablet formulations was studied under an atmosphere of nitrogen using a thermogravimetric balance. To maximize the tendency of an interaction, binary mixtures (1:1 by weight) of drug and excipient and between excipients were utilized. Two new methods were employed to assess the change in reactivities, and the thermal behavior of the materials under investigation. In the first method, named the αs−αr method, the solid state reactivity of the sample was compared to that of a reference. The term α refers to the extent of the reaction. The second method is called the W p W t method. In this method, the effect of the excipients on the decomposition pattern of ascorbic acid can be shown. The terms Wp and Wt refer to the percentage of residual solid material obtained experimentally (Wp) and theoretically (Wt). The ratio W p W t is reported at various values of temperature.

The kinetic parameters needed to describe the decomposition of calcium carbonate are obtained by a method which avoids the direct use of the Arrhenius parameters, the pre-exponential term A and the energy of activation E . It is shown that the approach is amenable to both an exact differential and integral analysis which carries certain advantages over existing methods. If needed, the method can be extended to allow the calculation of the Arrhenius parameters A and E , and in addition will show any dependence of E upon the fraction decomposed α, although it might be argued that the dependence of E is really upon the temperature.

It has been demonstrated that thermogravimetry can be used to determine various ratios of cholesterol, calcium carbonate and calcium oxalate in synthetic mixtures. The individual mass losses occur at sufficiently different temperatures for them to be unambiguously assigned to a specific decomposition reaction. The study has been extended to investigate the composition of some 20 natural gallstones, all of which contained cholesterol as the main component. Cholesterol was found to decompose in a single well defined step. Rising temperature experiments were conducted to ascertain the Arrhenius parameters. The kinetics of degradation was unaffected by the presence of the other constituents.

The behavior of aspirin in the presence of tablet excipients and in the presence and absence of moisture was investigated. The methods used for investigation were differential thermal analysis (DTA), thermogravimetry (TG), and direct ionization probe mass spectrometry (DIP-MS). In addition, the degradation of aspirin in the absence of moisture was investigated by TG, and the residue after the first decomposition on the TG curve was subjected to DIP-MS. A degradation mechanism for dry aspirin is postulated. Aspirin in tablet form was shown to be stabilized in the presence of increasing amounts of corn starch. These and related studies on the shelf-life of pharmaceutical products indicate possible interactions between the active ingredient and other ingredients of product formulations.