INVESTIGATION ON THERMAL STABILITY AND PURITY DETERMINATION OF TWO ANTIHYPERTENSIVE DRUGS, VALSARTAN AND LOSARTAN POTASSIUM

Objective: The thermal behavior of two antihypertensive drugs: Valsartan (VAL) and Losartan potassium (LOS) was investigated using different thermal techniques. These include thermogravimetry (TGA), derivative thermogravimetry (DTG) and differential scanning calorimetry (DSC).Methods: Thermogravimetric data obtained from first step of decomposition of valsartan and losartan allowed the determination of kinetic parameters such as activation energy (Ea), frequency factor (A), order of reaction (n) and enthalpy of decomposition (∆H). The purity of valsartan and losartan were determined by differential scanning calorimetry. Results: The thermal degradation of losartan and valsartan was followed a first-order kinetic behavior and evaluation of the relative thermal stabilities showed that LOS is more thermally stable than VAL. The decomposition modes were investigated and the fragmentation pathway of losartan was taken as example, to correlate the thermal decomposition with mass spectrometry. The purity of valsartan and losartan determined by differential scanning calorimetry was found to be 99.84 % and 99. 91 %, respectively, which was in good agreement with the pharmacopoeial results. Conclusion: Thermal analysis justifies its application in quality control of pharmaceutical compounds due to its simplicity, sensitivity and low operational costs.Â

Thermoanalytical Investigation of Terazosin Hydrochloride

Purpose: Thermal analysis (TGA, DTG and DTA) and differential scanning calorimetry (DSC) have been used to study the thermal behavior of terazosin hydrochloride (TER). Methods: Thermogravimetric analysis (TGA/DTG), differential thermal analysis (DTA) and differential scanning calorimetry (DSC) were used to determine the thermal behavior and purity of the used drug. Thermodynamic parameters such as activation energy (E*), enthalpy (H*), entropy (S*) and Gibbs free energy change of the decomposition (G*) were calculated using different kinetic models. Results: The purity of the used drug was determined by differential scanning calorimetry (99.97%) and specialized official method (99.85%) indicating to satisfactory values of the degree of purity. Thermal analysis technique gave satisfactory results to obtain quality control parameters such as melting point (273 ºC), water content (7.49%) and ash content (zero) in comparison to what were obtained using official method: (272 ºC), (8.0%) and (0.02%) for melting point, water content and ash content, respectively. Conclusion: Thermal analysis justifies its application in quality control of pharmaceutical compounds due to its simplicity, sensitivity and low operational costs. DSC data indicated that the degree of purity of terazosin hydrochloride is similar to that found by official method

Novel Solid State Properties of Drugs, Polymers and Various Chemicals by Thermal and Analytical Techniques

I have observed unique variations in AC electrical conductivity of solids by dielectric analysis (DEA or DETA) when studied with respect to temperature and frequency. A wide range of solids were examined for this study e.g. organics, polymers, carbohydrates, API\u27s (active pharmacy ingredients) and amino acids. Experimental results clearly show novel dielectric behavior of a linear increase in a log ionic conductivity vs. temperature in the pre-melt (20 to 30oC below the melt temperature) and melt transition regions. We have differentiated the solids which show the conductivity variations in pre-melt from those which do not e.g. pre-melt conductivity variations observed with polar polymers such as nylons and acetal vs. not observed in nonpolar polymers such as polyethylene, polypropylenes and long chain alkanes e.g. tetraconsane and pentacosane. Isothermal dielectric analysis was used to study the cause of this variation in solids which yielded a polarization time property. The effect of various experimental factors on the results such as the effect of heating rate, varying the frequency, and sample size on the dielectric variations in the pre-melt temperature range have been studied. 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 E928-08 Standard Test Method for Purity by Differential Scanning Calorimetry (DSC) was employed to verify the purity of the experimental chemicals used in this study e.g. Acetanilide, Acetophenitidine and Vanillin. Activation energies were calculated based on Arhennius behavior to better interpret the changes in the solid. 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 studies done by scanning electron microsc

Novel Solid State Properties of Drugs, Polymers and Various Chemicals by Thermal and Analytical Techniques

I have observed unique variations in AC electrical conductivity of solids by dielectric analysis (DEA or DETA) when studied with respect to temperature and frequency. A wide range of solids were examined for this study e.g. organics, polymers, carbohydrates, API\u27s (active pharmacy ingredients) and amino acids. Experimental results clearly show novel dielectric behavior of a linear increase in a log ionic conductivity vs. temperature in the pre-melt (20 to 30oC below the melt temperature) and melt transition regions. We have differentiated the solids which show the conductivity variations in pre-melt from those which do not e.g. pre-melt conductivity variations observed with polar polymers such as nylons and acetal vs. not observed in nonpolar polymers such as polyethylene, polypropylenes and long chain alkanes e.g. tetraconsane and pentacosane. Isothermal dielectric analysis was used to study the cause of this variation in solids which yielded a polarization time property. The effect of various experimental factors on the results such as the effect of heating rate, varying the frequency, and sample size on the dielectric variations in the pre-melt temperature range have been studied. 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 E928-08 Standard Test Method for Purity by Differential Scanning Calorimetry (DSC) was employed to verify the purity of the experimental chemicals used in this study e.g. Acetanilide, Acetophenitidine and Vanillin. Activation energies were calculated based on Arhennius behavior to better interpret the changes in the solid. 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 studies done by scanning electron microsc

Thermally induced degradation of citrus pectins during storage – Alterations in molecular structure, colour and thermal analysis

Commercial citrus pectins (17 samples from 3 different suppliers) were stored at 60 °C and 80% humidity for two weeks. Molecular parameters (galacturonan content, degree of methoxylation, intrinsic viscosity), colour and behaviour in thermal analysis (DSC and TG) were tested and the results were compared with those of model pectins prepared under laboratory conditions from a previous study. Whereas the molecular parameters and colour of both groups changed similarly, considerable differences in the thermal analysis were found not only between model pectins and commercial pectins but also between commercial samples from different suppliers. It seems that varying processing conditions between laboratory preparations and industrial processing as well as differences in industrial scale processing influence the pectin properties and their degradation during storage. All commercial citrus pectin samples were strongly demethoxylated and depolymerised, former high-methoxylated pectins with degree of methoxylation (DM) > 50% became low-methoxylated with DM < 50% and some low-methoxylated samples afterwards had a DM close to pectic acid. As a result, also their gelation properties changed markedly. For pectin producing and applying companies it might be essential to check the properties of pectins after longer storage under unfavourable conditions. As a consequence, a variation of the gelation conditions for pectins after storage might be necessary

CHARACTERIZATION OF LINAGLIPTIN USING ANALYTICAL TECHNIQUES

Linagliptin (LGT) is a member of the class of gliptins that inhibit the enzyme dipeptidyl-peptidase-4. They are used to reduce glucose blood levels in patients with type 2 Diabetes mellitus. Due to its recent development and launching on the market, LGT has no official compendium monograph, national or international, or available registries for the qualitative determination of this drug. The objective of this work was to characterize LGT by using thermal techniques, nuclear magnetic resonance, mass and infrared spectrometry, liquid chromatography and ultraviolet spectrophotometry to be used as a chemical reference substance. The range and melting point obtained are in accordance with that described in the literature. The main groups of LGT molecule were observed in infrared spectroscopy and the molecular ion m/z 473.25 ratio was found in mass spectroscopy analysis. In UV spectroscopy, the maximum wavelength absorption of the substance in different solvents can be observed. The chromatographic methods provide selectivity for LGT and can be used to analyze it qualitatively. The proposed conditions have been successfully applied for identification and qualitative analysis of LGT as a chemical reference substance, contributing to studies of this gliptin, and to the quality control of medicines that contain it.Linagliptin (LGT) is a member of the class of gliptins that inhibit the enzyme dipeptidyl-peptidase-4. They are used to reduce glucose blood levels in patients with type 2 Diabetes mellitus. Due to its recent development and launching on the market, LGT has no official compendium monograph, national or international, or available registries for the qualitative determination of this drug. The objective of this work was to characterize LGT by using thermal techniques, nuclear magnetic resonance, mass and infrared spectrometry, liquid chromatography and ultraviolet spectrophotometry to be used as a chemical reference substance. The range and melting point obtained are in accordance with that described in the literature. The main groups of LGT molecule were observed in infrared spectroscopy and the molecular ion m/z 473.25 ratio was found in mass spectroscopy analysis. In UV spectroscopy, the maximum wavelength absorption of the substance in different solvents can be observed. The chromatographic methods provide selectivity for LGT and can be used to analyze it qualitatively. The proposed conditions have been successfully applied for identification and qualitative analysis of LGT as a chemical reference substance, contributing to studies of this gliptin, and to the quality control of medicines that contain it

Simultaneous differential scanning calorimetry – synchrotron X-ray powder diffraction : a powerful technique for physical form characterisation in pharmaceutical materials

© 2016 American Chemical Society. We report a powerful new technique: hyphenating synchrotron X-ray powder diffraction (XRD) with differential scanning calorimetry (DSC). This is achieved with a simple modification to a standard laboratory DSC instrument, in contrast to previous reports which have involved extensive and complex modifications to a DSC to mount it in the synchrotron beam. The high-energy X-rays of the synchrotron permit the recording of powder diffraction patterns in as little as 2 s, meaning that thermally induced phase changes can be accurately quantified and additional insight on the nature of phase transitions obtained. Such detailed knowledge cannot be gained from existing laboratory XRD instruments, since much longer collection times are required. We demonstrate the power of our approach with two model systems, glutaric acid and sulfathiazole, both of which show enantiotropic polymorphism. The phase transformations between the low and high temperature polymorphs are revealed to be direct solid-solid processes, and sequential refinement against the diffraction patterns obtained permits phase fractions at each temperature to be calculated and unit cell parameters to be accurately quantified as a function of temperature. The combination of XRD and DSC has further allowed us to identify mixtures of phases which appeared phase-pure by DSC

Study of Drug Delivery Behavior Through Biomembranes Using Thermal and Bioanalytical Techniques

This Master of Science thesis encompasses two projects in chemical pharmaceuticals. The first is a study of excipients and the added new information collected beyond Thermal Gravimetric Analysis and Differential Scanning Calorimetry from Dielectric Analysis. These new properties enhance our global knowledge of excipients by thermal analytical methods. Excipients, the inactive ingredients in formulated drugs, aid different functions of the active pharmacy ingredient, the drugs. Low temperature transitions, by DEA including melting of frozen solvents, e.g. water, are more definitive than observed by low temperature DSC. Millions of dollars are expended annually on pharmaceutical testing to qualify excipients for fully formulated drugs, medicines and active ingredients. To understand the action of the excipients in the human body at body temperature of 37°C, the study of their individual and interactive properties are desirable. DEA DSC and Thermal Gravimetric analysis (TGA) methods are employed to screen the most widely used drug excipients. In this study the following excipients were examined by DEA: cotton seed oil, mannitol, peanut oil, polyethylene glycol, sugar, sodium lauryl sulfate, sodium starch glycolate, sodium stearate, canola oil, and anhydrous lactose, benzoic acid and vanillin. The comparison of DSC and DEA thermal curves for each excipient indicates that major endothermic events have occurred e.g., volatilization or melting of the excipient are viewed as fundamental DEA properties. These properties are the rise in permittivity and dielectric loss factor. The focus of this project was to learn to prepare, examine and interpret the resulting variations. The electrical conductivity (e * frequency* constant), permittivity (e\u27) and tan delta value (e /e\u27) are used to enhance the characterization of the excipient. The second, and major project for this thesis, is to evaluate bipolar disorder drug transport with and without an applied electric field of 10V mm-1. Drug delivery was tested with several