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Antipsychotics are a class of psychiatric medication that is primarily effective at reducing psychosis symptoms, particularly in schizophrenia and bipolar disorders. This study aims to formulate mixtures of the antipsychotic drugs quetiapine fumarate (QUE), nortriptyline (NOR), propranolol (PROP) and haloperidol (HAL) with excipients urea, niacin (NIA) and niacinamide (NIM) to obtain an enhanced bioavailability and therapeutic effect. The mixtures were prepared by the solvent method and are characterized by various analytical techniques such as differential scanning calorimetry, wide angle X-ray diffraction, scanning electron microscopy and dissolution studies. Out of the various mixtures that have been prepared and tested, five of them showed eutectic behavior and their eutectic points are as follows: quetiapine fumarate–urea (QUE–UREA) 20–80, w/w; nortriptyline–niacin (NOR–NIA) 70–30, w/w; propranolol–niacin (PROP–NIA) 80–20, w/w; propranolol–niacinamide (PROP–NIM) 40–60, w/w; and haloperidol–niacinamide (HAL–NIM) 20–80, w/w. DSC investigation has revealed the formation of an eutectic system and the phase diagrams and Tamman’s triangle construction along with the hot-stage microscopy confirmed their melting points. PXRD study indicated no chemical interaction between either of the mixtures, while SEM study showed the size reduction in these mixtures that has been achieved. In vitro studies of the five mixtures showed an appreciable increase in the dissolution rate compared to that of the drug alone. In conclusion, five simple eutectic mixtures have been formulated by the solvent method and were found to show better dissolution rates than that of the pure form of the drugs, thus improving the bioavailability of these poorly water-soluble drugs.

We have observed unique variations in AC electrical conductivity of solids when studied with respect to temperature, time, and frequency. A wide range of solids were examined for this study e.g., organics, polymers, carbohydrates, active pharmacy ingredients (APIs), and amino acids. The observed dielectric analysis conductivity for this great number of organic materials follows an Arrhenius plot of log polar ionic conductivity which is linearly related to reciprocal temperature and the correlation of coefficient is 0.992–0.999. These experimental observations support the polaron hopping conduction model. Experimental results clearly show novel dielectric behavior of a linear increase in a log ionic conductivity versus temperature in the pre-melt/solid-state transition regions. We have differentiated the solids which show the conductivity variations in pre-melt from those which do not. Isothermal dielectric analysis was used to study the cause of this variation in solids which yielded the measure of behavior, i.e., the polarization time property. We have also studied the effect of various experimental factors (e.g., moisture and purity) on the results. Correlating dielectric with calorimetric analyses gave us a better understanding of solid-state properties. Calorimetric analysis was used to assure that the observed variations in the solid-state properties are not due to moisture or impurities present in the sample. The ASTM E698 “purity method” was employed to verify the purity of the chemicals. Activation energies were calculated based on Arrhenius behavior to better interpret the solid-state properties. As the different chemicals were heat–cool cycled they were more amorphous, as evidenced by the decreasing activation energy for charge transfer with an increasing amorphous content.

Morphological and thermodynamic transitions in drugs as well as their amorphous and crystalline content in the solid state have been distinguished by thermal analytical techniques, which include dielectric analysis (DEA), differential scanning calorimetry (DSC), and macro-photomicrography. These techniques were used successfully to establish a structure versus property relationship with the United States Pharmacopeia standard set of active pharmaceutical ingredient (API) drugs. A distinguishing method is the DSC determination of the amorphous and crystalline content which is based on the fusion properties of the specific drug and its recrystallization. The DSC technique to determine the crystalline and amorphous content is based on a series of heat and cool cycles to evaluate the drugs ability to recrystallize. To enhance the amorphous portion, the API is heated above its melting temperature and cooled with liquid nitrogen to −120 °C (153 K). Alternatively a sample is program heated and cooled by DSC at a rate of 10 °C min−1. DEA measures the crystalline solid and amorphous liquid API electrical ionic conductivity. The DEA ionic conductivity is repeatable and differentiates the solid crystalline drug with a low conductivity level (10−2 pS cm−1) and a high conductivity level associated with the amorphous liquid (106 pS cm−1). The DSC sets the analytical transition temperature range from melting to recrystallization. However, analysis of the DEA ionic conductivity cycle establishes the quantitative amorphous and crystalline content in the solid state at frequencies of 0.10–1.00 Hz and to greater than 30 °C below the melting transition as the peak melting temperature. This describes the “activation energy method.” An Arrhenius plot, log ionic conductivity versus reciprocal temperature (K−1), of the pre-melt DEA transition yields frequency dependent activation energy (E a, J mol−1) for the complex charging in the solid state. The amorphous content is inversely proportional to the E a where the E a for the crystalline form is higher and lower for the amorphous form with a standard deviation of ±2%. There was a good agreement between the DSC crystalline melting, recrystallization, and the solid state DEA conductivity method with relevant microscopic evaluation. An alternate technique to determine amorphous and crystalline content has been established for the drugs of interest based on an obvious amorphous and crystalline state identified by macro-photomicrography and compared to the conductivity variations. This second “empirical method” correlates well with the “activation energy” method.

The current United States Pharmacopeia (USP) test for the disintegration of drug tablets does not measure initial disintegration times and does not adequately describe tablet disintegration mechanisms. An Isothermal Mechanical Analysis (IsoTMA) method meeting USP specifications has been developed to measure the initial time and rate of drug disintegration. TMA monitors the physical dimension of the formulated drug tablet as a function of time, temperature, applied stress, and pH. TMA can be used to measure the swelling, shrinkage, or disintegration of a formulated tablet in a specified fluid. The focus of this study is to validate an efficient and precise IsoTMA method to measure dimensional stability of solid dose tablets. The precision of the method along with the effect of pH (1–10) and temperature (25–37 °C) on the rate of delivery was determined for nine drugs. Graphical representations of dimensional changes over time were created and compared. Drug delivery in a specific liquid medium was measured by UV analysis for the active pharmaceutical ingredient. An increase in temperature decreased the disintegration time and increased the disintegration rate (mm/min). For the drugs that are studied in this article, pH did not have an appreciable effect on the rate of disintegration.

Novel dielectric behavior of a linear increase in ionic conductivity prior to melt temperature was observed for active pharmaceutical ingredients (APIs), organic chemicals, amino acids, and carbohydrates. Though, there are solids like polyolefins and long chain organic compounds (tetracosane, pentacosane) which do not exhibit this premelt behavior (i.e., the temperature where the onset of increase in ionic conductivity to melt temperature). We have discovered novel electrical conductivity properties and other physical analytical variations which can lead to unique synthetic routes of certain chemical entities. The above-mentioned unique variations are not related to solid–solid transitions which are quite often observed in pharmaceutical crystalline solids. These new properties are related to amorphous crystalline behavior of a solid. We have also studied the effect of various experimental variables: such as amount of mass tested, applied frequency at a given electric field and heating rate, which results in varying the onset temperature of the increase in ionic conductivity. Melting of the solids was correlated using differential scanning calorimetry (DSC). Activation energies for all the solids were measured in the premelt region using an Arrhenius plot at a specific frequency since we observed changes in the conductivity with frequency. This study focused on frequencies 0.1 to 10 Hz, since the conductivity at these frequencies related to surface analysis. This new physical properties are leading to new electro synthetic procedures to modify or prepare chemicals.

We study the solid-on-solid interface model above a horizontal wall in three dimensional space, with an attractive interaction when the interface is in contact with the wall, at low temperatures. There is no bulk external field. The system presents a sequence of layering transitions, whose levels increase with the temperature, before reaching the wetting transition., Comment: 61 pages, 6 figures. Miscellaneous corrections and changes, primarily in Section 4. Figure 5 added.

A eutectic is formed from a mixture of two or more solids and has a melting point lower than that of each of its constituents. It is generally represented by a phase diagram where the liquid and solid phases impact upon each other with a value known as the eutectic point. In pharmaceuticals, poor water solubility is a major obstacle for releasing new dosage forms into the market. Eutectic formation overcomes these problems. Preparation of a phase diagram by Differential Scanning Calorimetry can determine eutectic properties, but it is tedious. A modified Van't Hoff (VH) equation was used in this study. Devalina Law developed a dimensionless index for the VH equation. The difference in melting points of an excipient polymer and drug are divided by the slope of the VH equation. In previous studies, five excipient-drug compositions were evaluated. The final index relationship was in good agree- ment except for the salt, quinine sulfate. In order to test the validity of the VH index, further studies of PEG with ace- tylsalicylic acid, acetaminophen, diflunisal, dimenhydri- nate, ketoconazole, and mefenamic acid were performed.

We consider a polymer with configuration modeled by the path of a Markov chain, interacting with a potential $u+V_n$ which the chain encounters when it visits a special state 0 at time $n$. The disorder $(V_n)$ is a fixed realization of an i.i.d. sequence. The polymer is pinned, i.e. the chain spends a positive fraction of its time at state 0, when $u$ exceeds a critical value. We assume that for the Markov chain in the absence of the potential, the probability of an excursion from 0 of length $n$ has the form $n^{-c}\phi(n)$ with $c \geq 1$ and $\phi$ slowly varying. Comparing to the corresponding annealed system, in which the $V_n$ are effectively replaced by a constant, it is known that the quenched and annealed critical points differ at all temperatures for $3/22$, but only at low temperatures for $c3/2$ with arbitrary temperature we provide a new proof that the gap is positive, and extend it to $c=2$., Comment: 33 pages

Eugenol is the main volatile compound extracted oil from clove bud, Syzygium aromaticum L., and used in traditional medicine, as a bactericide, fungicide, anesthetic, and others. Its extraction was performed using hydrodistillation which is the most common extraction technique. Its components and thermal behavior were evaluated using gas chromatography (GC) and differential scanning calorimetry (DSC), which provide a better characterization of these natural compounds. This extracted product was compared to the standard eugenol results. The GC results suggested ~90% eugenol was found in the total extracted oil, and some of its boiling characteristics were 270.1 °C for peak temperature and 244.1 J g−1 for the enthalpy variation.

Eugenol is an allyl chain-substituted guaiacol in the biosynthesized phenylpropanoid compound class derived from Syzygium aromaticum L. and widely used in folk medicine. Nonetheless, its pharmacological use is limited by some problems, such as instability when exposed to light and high temperature. In order to enhance stability, the eugenol molecule was structurally modified, resulting in eugenyl acetate. The eugenyl acetate’s thermal behavior and crystal structure was then characterized by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) and compared to a commercial sample.

Essential oils are good candidates for the substitution of conventional medicinal treatments. Many articles and patents for their use have been published in recent years. The most attractive aspects of using essential oils as medicaments are their natural source and rapid permeability. Besides permeability, the solubility behavior of a drug is a key determinant of its oral bioavailability. Based on these characteristics, the aim of this study was to synthesize an essential oil derivative compound, using the raw oil extracted from Syzygium aromaticum L., without previous purification. The Eugenol molecular modification may diminish the problems of water solubility and bioavailability. The Eugenyl acetate molecule was characterized and its molecular modification investigated, including its structural properties and stereochemistry. This study was performed applying techniques, such as carbon-13 nuclear magnetic resonance spectroscopy (C-13 NMR), X-ray crystallographic analysis (XRD), powder X-ray diffraction (PXRD) and microscopic recording. Eugenol and its structure have been known for many years, where as Eugenyl acetate’s structure has never been elucidated nor confirmed until now.

This project investigated the interaction between poly-L-lactic acid (PLLA) and several therapeutic agents. Low percentage crystallinity PLLA (melt-pressed, molded and drawn) was studied. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) were used to characterize the crystallinity and thermal properties in a thermal cycling process. Repeatable melting and crystallization events were observed. The thermal properties of a drug-polymer combination using PLLA and an acidic, basic, neutral and zwitterionic material were investigated. A sufficient quantity of the drug must be present in the polymer to be observed thermally. Release of atropine sulfate from a PLLA tablet showed a two-phase process.

Differential scanning calorimetry (DSC) is a thermal analytical tool for preformulation studies. Extrapolated melting temperature (TP) and heat of fusion (ΔHf) can be used as parameters for optimizing the DSC performance. Two model pharmaceuticals acetaminophen and nicotinamide are used in this study. Using a factorial design for the experimental model and matrix analysis the results, the effect of sample mass, heating rate and the nitrogen flow rate were evaluated on the ΔHf values and TP values. Two levels for each of the procedural variables were used as a balanced experimental design with two sample sizes, two heating rates and two nitrogen flow rates. It was found that the change in the heating rate caused significant changes in the ΔHf values but not the Tp values for acetaminophen. However, no significant effect was found for the Tp value but ΔHf value was affected to a certain extent for nicotinamide.

We continue our study of colligative properties of solutions initiated in math-ph/0407034. We focus on the situations where, in a system of linear size $L$, the concentration and the chemical potential scale like $c=\xi/L$ and $h=b/L$, respectively. We find that there exists a critical value $\xit$ such that no phase separation occurs for $\xi\le\xit$ while, for $\xi>\xit$, the two phases of the solvent coexist for an interval of values of $b$. Moreover, phase separation begins abruptly in the sense that a macroscopic fraction of the system suddenly freezes (or melts) forming a crystal (or droplet) of the complementary phase when $b$ reaches a critical value. For certain values of system parameters, under ``frozen'' boundary conditions, phase separation also ends abruptly in the sense that the equilibrium droplet grows continuously with increasing $b$ and then suddenly jumps in size to subsume the entire system. Our findings indicate that the onset of freezing-point depression is in fact a surface phenomenon., Comment: 27 pages, 1 fig; see also math-ph/0407034 (both to appear in JSP)

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.

Snake skin is a viable and readily available material as a model for human skin. Pharmaceutical applications use shed snake skin to study the effects of sunscreens on exposure to UV radiation (e.g. benzophenone on Boa integument). In order to understand the effects of radiation or drug transport through this model skin, one must determine its basic physical properties. This preliminary study evaluated two types of snake skin, namely Cuban Boa a 'dark' skin (Epicrates angulifer) and Green tree python a 'light' skin (Morelia viridis). Previous studies by other investigators have used pig, rabbit and snake skin as a human skin substitute. The structure of both snake skins was comparable based on IR spectroscopy and were functionally amino acids and moisture. Photomicrography by light and scanning electron microscopy revealed strong anatomic similarities. Morphologically there were two structures visible, namely a cellular and hinge-fibrous area. The thermal techniques indicated a phase transition at 35-75°C, which is associated with lipid melting. There was an 8 and 12% mass loss for the light skin and dark skin, respectively, which is interpreted, in part, as moisture loss at

Five poorly soluble drugs namely hydrochlorothiazide, menadione, propylthiouracil, quinine sulfate and sulfamerazine were used to evaluate the ability of an index (Ic) based on the van't Hoff equation to predict the eutectic composition at a higher heating rate than previously published. The term Ic is a dimensionless index which has been defined in the literature and is used to predict eutectic composition. This current work uses this study to determine if the correlation holds true at the higher heating rate of 10°C min-1. The maximum deviation was observed for quinine sulfate, for which the predicted eutectic composition was 10% lower than what was observed with the DSC. It can be concluded that the Index developed here has a good correlation with the experimentally determined eutectic composition.

This study attempts to identify the degradative process which folic acid undergoes in the solid-state under thermal stress. In order to facilitate the process, the various pieces of the chemical structure, namely, p-amino benzoic acid, pterin and glutamic acid as both its d- and l-isomers were investigated as separate entities. These structured solid-state pieces were then compared to the composite solid state folic acid degradative curves in order to identify the peaks seen and provide direction for the interpolation of the degradative mechanism. 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 spectroscopy, mass spectroscopy and X-ray diffraction 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 degrading to carbon fragments and that further identification was not necessary.

The present study was aimed at determining the kinetics of evaporation and establishing vapor pressure curves for both single and multi-component systems by thermogravimetry (TG) and differential scanning calorimetry (DSC). Essential oils (e.g. lavender oil, orange oil, clove oil and eucalyptus oil, etc.) are typically multi-component systems consisting of various volatile pure components (e.g. linalyl acetate, limonene, cinnamaldehyde, etc.) which resemble single component systems. In this study linalyl acetate was taken as the calibration compound for TG. The vapor pressure curves for the pure substances were plotted using TG and vapor pressure plots for clove oil and eucalyptus oil were constructed using DSC. The thermodynamic and kinetic parameters of the pure compounds were compared to that of the multi-component systems to quantitatively and qualitatively measure the influence of different compounds on each other. The k-value from the vapor pressure data for linalyl acetate was calculated as 112006 Pa kg0.5mol0.5s-1 m-2 K-0.5. The vapor pressure values were used to determine the Antoine constants using the SPSS 10.0 software.

We study the depinning transition of the $1+1$ dimensional directed polymer in a random environment with a defect line. The random environment consists of i.i.d. potential values assigned to each site of $\mathbb{Z}^2$; sites on the positive axis have the potential enhanced by a deterministic value $u$. We show that for small inverse temperature $\beta$ the quenched and annealed free energies differ significantly at most in a small neighborhood (of size of order $\beta$) of the annealed critical point $u_c^a=0$. For the case $u=0$, we show that the difference between quenched and annealed free energies is of order $\beta^4$ as $\beta\to 0$, assuming only finiteness of exponential moments of the potential values, improving existing results which required stronger assumptions., Comment: 22 pages. Changes to Proposition 3.8 make Proposition 4.1 unnecessary; minor corrections made

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.

We study the path properties of a random polymer attracted to a defect line by a potential with disorder, and we prove that in the delocalized regime, at any temperature, the number of contacts with the defect line remains in a certain sense "tight in probability" as the polymer length varies. On the other hand we show that at sufficiently low temperature, there exists a.s. a subsequence where the number of contacts grows like the log of the length of the polymer., Published in at http://dx.doi.org/10.1214/13-AAP930 the Annals of Applied Probability (http://www.imstat.org/aap/) by the Institute of Mathematical Statistics (http://www.imstat.org)

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.

We consider a polymer, with monomer locations modeled by the trajectory of a Markov chain, in the presence of a potential that interacts with the polymer when it visits a particular site 0. We assume that probability of an excursion of length $n$ is given by $n^{-c}\phi(n)$ for some $13/2$, at high temperature, the quenched and annealed curves differ significantly only in a very small neighborhood of the critical point--the size of this neighborhood scales as $\beta^{1/(2c-3)}$ where $\beta$ is the inverse temperature. For $c0$, for sufficiently high temperature the quenched and annealed curves are within a factor of $1-\epsilon$ for all $u$ near the critical point; in particular the quenched and annealed critical points are equal. For $c=3/2$ the regime depends on the slowly varying function $\phi$., Comment: 31 pages