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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.

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.

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.

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.

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.

Hydroxy benzoic acids were subjected to rising temperature thermogravimetric analysis. After optimizing the procedural variables, the kinetics of decomposition was determined and methyl paraben was taken as the calibration compound to characterize the evaporation patterns for the ortho and meta derivatives. The Eact values for ortho, meta and para derivatives were 64.8, 78.2, and 119.1 kJ mol–1, respectively. The Antoine and Langmuir equations were utilized to determine the coefficient of evaporation k, which was 124525±0.8, units being in the SI system. The vapor pressure plots were generated for the ortho and meta derivatives; ΔHvap for these two compounds were obtained as 66.7 and 80.4 kJ mol–1, respectively.

The effects of procedural variables on dolomite decomposition in carbon dioxide were investigated. The partial pressure of carbon dioxide causes dolomite decomposition to split into a two-stage process. It was observed that the first stage of dolomite decomposition is progressively displaced to higher temperatures with an increase in heating rate. However, the second stage is not affected significantly by changes in the heating rate. These studies also indicate that decrepitation analysis on dolomite in CO2 provides better information as compared to experiments in other atmospheres. The flow rate of the purge gas does not influence the thermal behavior of dolomite.