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The availability of suppositories in Hungary, especially in clinical pharmacy practice, is usually provided by extemporaneous preparations. Due to the known advantages of rectal drug administration, its benefits are frequently utilized in pediatrics. However, errors during the extemporaneous manufacturing process can lead to non-homogenous drug distribution within the dosage units. To determine the root cause of these errors and provide corrective actions, we studied suppository samples prepared with exactly known errors using both cerimetric titration and HPLC technique. Our results show that the most frequent technological error occurs when the pharmacist fails to use the correct displacement factor in the calculations which could lead to a 4.6% increase/decrease in the assay in individual dosage units. The second most important source of error can occur when the molding excess is calculated solely for the suppository base. This can further dilute the final suppository drug concentration causing the assay to be as low as 80%. As a conclusion we emphasize that the application of predetermined displacement factors in calculations for the formulation of suppositories is highly important, which enables the pharmacist to produce a final product containing exactly the determined dose of an active substance despite the different densities of the components.

Granulations of dimenhydrinate (DMH) were prepared using various concentrations of ethyl cellulose (EC) by the solid dispersion technique. Characterization was done using thermal analysis, powder X-ray diffraction, infrared spectroscopy, optical microscopy and dissolution studies. Humidity studies were performed to investigate the effect of moisture on the drug and solid dispersions. It was seen that the crystalline drug was converted into its amorphous form in all the granulations. There was no chemical interaction between the DMH and EC. The thermal decomposition of drug in the granules was not affected. Dissolution studies revealed that the drug release from the granulations was significantly reduced as compared to the pure drug. As the amount of ethyl cellulose increased, the drug release rate decreased and the drug release kinetics showed a better fit to zero-order kinetics. Humidity studies showed that the drug and granulations remained stable in conditions not exceeding 70%RH. At high humidity of 100%RH, there was formation of the hydrate crystal forms of the drug in the pure drug samples and granules with 1:1 DMH-EC content whereas the granules with higher polymer content did not show any significant changes indicating better drug stability in the granules.

Solid-state interaction between ibuprofen and nicotinamide was studied using thermal, spectroscopic, and microscopic techniques. Solubility enhancement was calculated by high-performance liquid chromatography and suspension was found to be the suitable choice of formulation. Ibuprofen-nicotinamide binary mixtures were prepared by solvent evaporation method. Differential scanning calorimetry was used to investigate the stoichiometry and thermal properties of the complex between ibuprofen and nicotinamide. A sharp, single endotherm was observed between the melting endotherms of the individual components at a composition of 60% ibuprofen and 40% nicotinamide (w/w). Several spectroscopic techniques such as ultraviolet-visible, Fourier transform infrared, nuclear magnetic resonance, and powder X-ray diffraction were used to investigate the type of interaction between the two components. Optical microscopy was performed to observe changes with regard to particle size and crystal habit. It was concluded that the interaction that occurred was Pi donor-Pi acceptor in nature and too weak to sustain the integrity of the complex in the liquid state. The solubility of ibuprofen was enhanced by 62 times in the suspension when the concentration of nicotinamide was 13.3 mg/mL. The suspension prepared in this study has potential of being a better medication for pain relief in patients with osteoarthritis.

The possibility of obtaining tolbutamide polymorphs was investigated using the solvents acetonitrile and 1-octanol. Tolbutamide is an oral hypoglycemic agent that exists in four polymorphic forms. Characterization of the various polymorphs was carried out by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), infrared spectroscopy (FTIR), optical microscopy and dissolution studies. Form A, crystallized from acetonitrile, resembled the form I polymorph, while form O, crystallized from 1-octanol, resembled the form III polymorph. Tablets of both form A and form O were produced at compression pressures of 2500 lbs and 5000 lbs using cornstarch and talc and were exposed to 40%, 75% and 95% RH conditions. DSC and PXRD studies did not show any significant drug-excipient interaction. Moreover, the change in the crystalline state of either form upon exposure to humidity was not evident. Dissolution studies showed a significantly lower drug release rate from form O tablets compressed at 5000 lbs pressure and exposed to 95% RH. Pressure and humidity had no significant effect on the dissolution profiles on the form A tablets. It was concluded that form A was the robust choice for further formulation development.

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.

The present study evaluates the effects of excipients, compression pressure, and relative humidity (RH) on the stability of sulfamerazine polymorphs (referred here as SMZ I and SMZ II) and their release from directly compressed tablets using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and dissolution analysis. SMZ I and SMZ II tablets were compressed with magnesium stearate (MGST), and microcrystalline cellulose (MCC) at 5000, 7500, and 10,000 lbs. pressures and stored at 40, 75, 95, and 100% RH conditions for 5 weeks. There were indications of possible drug-excipient interaction in the binary mixtures under different relative humidity conditions from the DSC data, but they could not be confirmed by PXRD because the crystal structures of the drug and excipients remained unaltered. The crystal structures of the polymorphs in the tablet also remained unaltered under the above conditions. There were, however, significant differences observed in the drug release properties of the two polymorphs. SMZ II was found in general to have a higher rate of drug release than SMZ I. Extensive gelation of MCC under higher moisture conditions, compression pressure during tableting, and inherent tabletability of the sulfamerazine crystals were factors that affected drug release. All these factors contributed towards prolonging the disintegration and deaggregation of the tablet particles and were therefore concluded to be the rate limiting steps for the dissolution process.

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 objective of this study was to develop and analyze an analytical method in order to evaluate preformulation candidates by their thermodynamic parameters and evaporation characteristics. Ortho, meta and tere-phthalic acids were chosen as model compounds. The relative advantages and disadvantages of a rapid thermogravimetric method have been studied in detail, which would aid in the preformulation characterization for pharmaceuticals. Methyl paraben was taken as the model compound for calibration, as its evaporation characteristics are well known. Using the Antoine and the Langmuir equation for evaporation conjointly, the parameter k, known as the coefficient of evaporation was determined. The value for this constant was validated by three methods simultaneously. Previously the use of such methods for compounds having uninhibited zero order evaporation has been documented. In the present study, phthalic acid was chosen as the model compound since its evaporation is a two-step overlapping phenomenon. In this study we have shown the use of Pressure Differential Scanning Calorimetry in separating such simultaneous endothermic processes. The Clausius-Clapeyron equation seemingly has anomalous behavior for vapor pressure over high temperature ranges. In this study a modification of the equation has been suggested to take into account the changes in the heat capacities that result due to high temperature effects. This study aims at documenting a concise method for rapid pharmaceutical characterization and suggests modifications for some basic thermodynamic parameters over higher temperature ranges.

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.

Characterization of formulation components in pre-formulation and formulation studies will be made easier if a rapid method to evaluate the evaporation characteristics of an ingredient in the formulation is developed. This study aims at providing a simple and rapid thermogravimetric method for 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 degrees C/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 the literature, and its selected thermodynamic parameters were evaluated using the Langmuir equation. The coefficient of vaporization (k macro) was determined to be 124,525+/-0.8, with units being reported in the S.I. system. The corresponding vapor-pressure plots were obtained for the remaining compounds and their Antoine constants calculated.

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.

Sedimentation of dilute pharmaceutical suspensions obeys Stokes's law, which assumes that there is no interaction between particles. The behavior of concentrated pharmaceutical suspensions is generally interpreted by use of modifications of Stokes's law that do not consider chemical interaction between particles. Properties of the medium itself, such as dielectric constant and surface tension, have not been included in the established equations. The present work shows that the dielectric constant of the medium has a distinct effect on the rate of sedimentation of the systems investigated.

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.

The problem concerned with delineating the behavior of concentrated suspensions may provide an opportunity to interpret the data by applying the Kozeny-Carman equation. This permeability equation is correlated with the Richardson-Zaki expression, and enables the variation of the Kozeny parameter, k, with suspension porosity to be established under sedimentation conditions. The variation of k with suspension composition is provided. The value of k previously determined when this method was applied to a wide variety of suspensions was shown to be greater than the approximate value of 5 normally quoted. The previous finding that the maximum sedimentation mass-transfer rate will never occur at a solids concentration greater than 25% vol. is tested using the experimental results.

The solubility of a series of compounds was determined in a wide polarity spectrum of normal aliphatic alcohols over a limited temperature range. The solutes chosen were the methyl through n ‐butyl p ‐hydroxybenzoates, several of these being useful preservatives. Solubility profiles were determined for these compounds and the effect of temperature upon their solubility behavior was investigated. The solubility of the solutes is expressed in several concentration notations; mole fraction plots showed a variable twin peak array as a function of the dielectric constant for the solutes studied. Since heats of fusion were available and data were generated as a function of temperature, ther‐modynamic parameters for these systems could be calculated. The relationship of these parameters to multiple solubility peak array is discussed.