Thermal Stability Of Folic Acid in the solid-state

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. This revised version was published online in August 2006 with corrections to the Cover Date.     

Characterization of some essential oils and their key components: Thermoanalytical techniques

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 kg^0.5mol^0.5s^-1 m^-2 K^-0.5. The vapor pressure values were used to determine the Antoine constants using the SPSS 10.0 software.This revised version was published online in November 2005 with corrections to the Cover Date.     

A statistical model for the optimization of dsc performance in the evaluation of drugs for preformulation studies

Differential scanning calorimetry (DSC) is a thermal analytical tool for preformulation studies. Extrapolated melting temperature (T_P) and heat of fusion (ΔH_f) 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 ΔH_f values and T_P 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 ΔH_f values but not the T_p values for acetaminophen. However, no significant effect was found for the T_p value but ΔH_f value was affected to a certain extent for nicotinamide.     

Characterization of crystalline and amorphous content in pharmaceutical solids by dielectric thermal analysis

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.     

Human cytokines characterized by dielectric thermal analysis, thermogravimetry, and differential scanning calorimetry

Malaria affects over 500 million people worldwide leading to 1–2 million deaths each year, the majority of whom are children. Four Plasmodium species cause malaria in humans. To properly diagnose, and correctly treat malarial infections, accurate diagnosis of infection is required. Proper diagnosis of infection will result in a reduction of morbidity, mortality, and of drug resistant parasites. However, the current tests for malaria diagnosis do not efficiently identify the appropriate human and parasite biomarkers associated with disease. Detection of specific inflammatory mediators such as cytokines associated with malaria pathogenesis will aid the determination of disease progression, disease prognosis, and the early diagnosis of malaria infection. In this study, we used dielectric thermal analysis (DETA), thermogravimetric analysis, and differential scanning calorimetry (DSC) to characterize five human cytokines (IL-1α, IL-2, IL-4, IL-6, and IL-10), to demonstrate how their thermoanalytical properties can be investigated for sensor design. Analysis for DETA was performed at a frequency range of 0.1–300,000 Hz. Permittivity and loss factor measurements were used to calculate tan δ values. Peak frequencies were used to determine dielectric signatures for each cytokine. The peak frequencies were different for each cytokine analyzed. In addition, activation energies were frequency dependent for IL-2 but frequency independent for the remaining four cytokines. Cytokines were also examined using DSC which established variance in heat of crystallization and heat of fusion of solvent among the five cytokines. A noticeable differentiation was observed with IL-1α among the other four cytokines when analyzed using trend analysis. Detection of unique dielectric signals will aid development of sensitive dielectric sensors capable of detecting cytokines in various human samples.     

Sesquiterpenes produced by Pestalotiopsis microspora HF 12440 isolated from Artocarpus heterophyllus

Abstract

A drimane-type sesquiterpene, (+)-dendocarbin L (1) together with two bisabolane-type sesquiterpenes, (+)-sydonic acid (2) and (+)-sydowic acid (3) were isolated from the mycelium of Pestalotiopsis microspora HF 12440, an endophytic fungus from the stem of Artocarpus heterophyllus. The structures of all compounds were elucidated using spectroscopic methods and by comparison with the literature. Compound 1 was isolated from the fungi for the first time, compounds 2 and 3 were firstly obtained from this endophytic fungus. Compound 3 showed cytotoxicity (IC₅₀ 2.56?μg/mL) against murine leukemia P-388 cells.     

Thermal behavior of verapamil hydrochloride and its association with excipients

The thermal properties of verapamil hydrochloride (VRP) and its physical association as binary mixtures with some common excipients were evaluated. Thermogravimetry (TG) was used to determine the thermal mass loss, as well as to study the kinetics of VRP thermal decomposition, using the Flynn-Wall-Ozawa model. Based on their frequent use in pharmacy, five different excipients (microcrystalline cellulose, magnesium stearate, hydroxypropyl methylcellulose, polyvinylpyrrolidone and talc) were blended with VRP. Samples were prepared by mixing the analyte and excipients in a proportion of 1:1 (m/m). DSC curves for pure VRP presented an endothermic event at 143 ± 2 °C (ΔH_melt = 132 ± 4 J g⁻¹), which corresponds to the melting (literature T_m = 143.7 °C, ΔH_melt = 130.6 J g⁻¹). Comparisons among the observed results for each compound and their binary physical mixtures presented no relevant changes. This suggests no interaction between the drug and excipient.     

Thermal behavior and structural properites of plant-derived eugenyl acetate

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.     

Dielectric classification of <Emphasis Type="Italic">D</Emphasis>-and <Emphasis Type="Italic">L</Emphasis>-amino acids by thermal and analytical methods

Dielectric analysis (DEA), supported by thermogravimetric analysis (TG), differential scanning calorimetry (DSC), powder X-ray diffraction analysis (PXRD) and photomicrography, reveal the chiral difference in the amino acids. The acids are classified as dielectric materials based on their structure, relating chirality to the vector sum of the average dipole moment, composed of the constant optical (electronic) and infra-red (atomic) polarizabilities, as well as dipole orientation. This study encompasses 14 L-and D-amino acid isomers. Physical properties recorded include AC electrical conductivity, charge transfer complexes, melting, recrystallization, amorphous and crystalline phases, and relaxation spectra, activation energies and polarization times for the electrical charging process.