Thermal characterization of indinavir sulfate using TG,DSC and DSC-photovisual

The object of the present work is to study the thermal characteristics of indinavir sulfate and to evaluate the quality of the raw materials. Indinavir A, B, C and reference samples were obtained from different suppliers and submitted to TG, DSC and DSC-photovisual analyses. TG/DTG curves indicated a desolvation and dehydration processes and were confirmed by DSC. According to the DSC curves the fusion took place at about 141–142°C for indinavir C and Reference sample B and about 146–149°C for the others. DSC-photovisual showed insoluble raw materials for indinavir C at 160°C. Indinavir sulfate is highly hygroscopic drug which requires attention during storage and manufacture by pharmaceutical industry.     

Characterization and compatibility study of desloratadine

Desloratadine (DL) is a selective antagonist of the histamine H₁ receptor, which has been widely used to treat allergic symptoms, and stands out from other drugs in this therapeutic class because it does not cause sedative effects. In the present study, the physico-chemical properties of DL were fully characterized using six analytical techniques such as Differential Scanning Calorimetry (DSC), Thermogravimetric analysis (TG/DTG), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, Powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The DSC curve shows a sharp endothermic event at 158.4 °C, and the TG/DTG curve presents two decomposition events between 178.4 and 451.9 °C. A compatibility study involving DL and nine pharmaceutical excipients generally used in pharmaceutical formulations was performed. Physical binary mixtures of DL with each excipient were prepared in a 1:1 (w/w) ratio. After preparation, the samples were analyzed immediately and the results reveal solid-state interaction with anhydrous lactose, microcrystalline cellulose, magnesium stearate, and stearic acid.     

Synthesis,characterization, and thermal study of solid-state alkaline earth metal mandelates,except beryllium and radium

Characterization, thermal stability, and thermal decomposition of alkaline earth metal mandelates, M(C₆H₅CH(OH)CO₂)₂, (M = Mg(II), Ca(II), Sr(II), and Ba(II)), were investigated employing simultaneous thermogravimetry and differential thermal analysis or differential scanning calorimetry, (TG–DTA or TG–DSC), infrared spectroscopy (FTIR), complexometry, and TG–DSC coupled to FTIR. All the compounds were obtained in the anhydrous state and the thermal decomposition occurs in three steps. The final residue up to 585 °C (Mg), 720 °C (Ca), and 945 °C (Sr) is the respective oxide MgO, CaO, and SrO. For the barium compound the final residue up to 580 °C is BaCO₃, which is stable until 950 °C and above this temperature the TG curve shows the beginning of the thermal decomposition of the barium carbonate. The results also provide information concerning the thermal behavior and identification of gaseous products evolved during the thermal decomposition of these compounds.     

Characterization of venlafaxine hydrochloride and compatibility studies with pharmaceutical excipients

The thermal analytical study of venlafaxine hydrochloride, a third generation antidepressant, was investigated using thermogravimetry (TG) and differential scanning calorimetry (DSC). The DSC curves have shown a sharp endothermic event at 211 °C and TG demonstrated a single stage of mass loss between 254 and 283 °C. Solid-state characterization was carried out by DRIFT, SEM, and XRPD demonstrating the drug physicochemical properties including crystallinity. Drug-excipient compatibility studies investigated by DSC have shown a possible physical interaction of the drug with magnesium stearate, microcrystalline cellulose and starch. Nevertheless, these results where not confirmed by DRIFT and SEM analyses.     

Thermal compatibility between hydroquinone and retinoic acid in pharmaceutical formulations

Thermogravimetry (TG) and differential scanning calorimetry (DSC) are used in pharmaceutical studies for characterization of drugs, purity, compatibility of formulations, identification of polymorphism, evaluation of stability, and thermal decomposition of drugs and pharmaceutical formulations. Hydroquinone (HQ) and products containing HQ have been widely used as depigmentation agents for lightening the skin. Retinoids are compounds that have the basic core structure of vitamin A and its oxidized metabolites, or synthetic compounds that share similar mechanisms of action as naturally occurring retinoids. Depigmentants and excipients were analyzed by TG and DSC. The dynamic thermogravimetric curves were obtained on a SHIMADZU thermobalance, model DTG-60, using an alumina crucible, at the heating rate of 10 °C min^?1, in the temperature range of 25–900 °C, under an atmosphere of nitrogen at 50 mL min^?1. The sample's mass was 10 ± 0.05 mg. The DSC curves were obtained using Shimadzu calorimeter, model DSC-60, using aluminum crucible, at the heating rate of 10 °C min^?1, in the temperature range of 25–400 °C. The thermogravimetric and calorimetric curves were analyzed using TASYS software SHIMADZU. In this study were found the interaction between retinoic acid (RA) and the following excipients: cetyl alcohol(CA), cetostearyl alcohol (CTA), glycerin(GLY), and dipropylene glycol (DPG), and that between HQ and the excipient, DPG. Therefore, additional studies are necessary to evaluate final formulations. Thermal analysis is an effective and reliable technique that can be used in the control of raw materials and pharmaceutical products, and for evaluating their employment potential in the development and characterization of products.     

Physicochemical characterization of dipeptidyl peptidase-4 inhibitor alogliptin in physical mixtures with excipients

Alogliptin (ALG) is a hypoglycemic drug used in diabetes which inhibits the enzyme dipeptidyl peptidase-4 (DPP-4), preventing the degradation of incretins, stimulating insulin secretion. The physicochemical characteristics of ALG were evaluated by differential scanning calorimetry (DSC), thermogravimetry (TG) and scanning electron microscopy equipped with energy-dispersive X-ray spectrometer (SEM/EDS). The compatibility studies were carried out between ALG and excipients (physical mixtures, 1:1) using DSC, TG, diffuse reflectance Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRPD) and hot-stage microscopy. ALG presented purity near to 99%, melted in the range of 179.4–187.2 °C, followed by decomposition which started in 198.0 °C. SEM/EMS analysis of ALG presented irregular crystals and traces of impurities as copper and lead. DSC investigations obtained by physical mixtures showed minor alterations in the melting ranges of ALG with mannitol, magnesium stearate and commercial tablets. Solubilization of ALG in the fused excipient was observed by hot-stage microscopy between mannitol and ALG, and in tablets. The interaction observed in the mixture with magnesium stearate is due to the melting of the excipient and drug separately, first the excipient and then the drug. FTIR showed additional bands related to the excipients. XRPD proved that ALG has a crystal form and no alterations in the ALG profile were observed after the mixtures. ALG was compatible with all excipients tested. These results were important to understand the characteristics, stability and compatibility of the drug, and proved to be useful in preformulation studies.

     

Investigation of the reaction mechanism and kinetics of production of anhydrous sodium metaborate (NaBO2) by a solid-state reaction

In this study, the solid-state reaction mechanism and kinetics were investigated for production of anhydrous sodium metaborate (NaBO₂), an industrially and technologically important boron compound. To assess the kinetics of solid-state production of NaBO₂, the chemical reaction between borax (Na₂B₄O₇) and sodium hydroxide (NaOH) was investigated by use of the thermal analysis techniques thermogravimetry (TG) and differential thermal analysis (DTA). DTA curves obtained under non-isothermal conditions at different heating rates (5, 10 and 20 °C/min), revealed five endothermic peaks corresponding to five solid-state reactions occurring at 70, 130, 295, 463, and 595 °C. The stages of the solid-state reaction used for production NaBO₂ were also analyzed by XRD, which showed that at 70 and 130 °C, Na₂B₄O₇ and NaOH particles contacted between the grains, and diffusion was initiated at the interface. However, there was not yet any observable formation of NaBO₂. Formation of NaBO₂ was initiated and sustained from 295 to 463 °C, and then completed at 595 °C; the product was anhydrous NaBO₂. Activation energies (E _a) of the solid-state reactions were calculated from the weight loss based on the Arrhenius model; it was found that in the initial stages of the solid-state reaction E _a values were lower than in the last three steps.     

Thermal decomposition and kinetics studies on poly(BDFAO/THF), poly(DFAMO/THF), and poly(BDFAO/DFAMO/THF)

The thermal behavior of kaolinite–urea intercalation complex was investigated by thermogravimetry–differential scanning calorimetry (TG–DSC), X-ray diffraction (XRD), and fourier transform infrared spectroscopy (FTIR). In addition, the interaction mode of urea molecules intercalated into the kaolinite gallery was studied by means of molecular dynamics simulation. Three main mass losses were observed at 136 °C, in the range of 210–270 °C, and at 500 °C in the TG–DSC curves, which were, respectively, attributed to (1) melting of the surface-adsorbed urea, (2) removal of the intercalated urea, and (3) dehydroxylation of the deintercalated kaolinite. The three DSC endothermic peaks at 218, 250, and 261 °C were related to the successive removals of intercalated urea with three different distribution structures. Based on the angle between the dipole moment vector of urea and the basal surface of kaolinite, the three urea models could be described as follows: (1) Type A, the dipole moment vector is nearly parallel to the basal surface of kaolinite; (2) Type B, the dipole moment vector points to the silica tetrahedron with the angle between it and the basal surface of kaolinite ranging from 20°to 40°; and (3) Type C, the dipole moment vector is nearly perpendicular to the basal surface of kaolinite. The three distribution structures of urea molecules were validated by the results of the molecular dynamics simulation. Furthermore, the thermal behavior of the kaolinite–urea intercalation complex investigated by TG–DSC was also supported by FTIR and XRD analyses.     

Determination of Anomalin and Deltoin in Seseli resinosum by LC Combined with Chemometric Methods

Liquid chromatography–chemometric methods [LC-Partial least squares (LC-PLS), LC-principle component regression (LC-PCR) and LC-artificial neural network (LC-ANN)] were developed for the determination of (?)-anomalin (ANO) and deltoin (DEL) in the root and aerial part of Seseli resinosum Freyn et Sint. (Umbelliferae). Firstly, chemometric conditions were optimized by testing different mobile phases at various proportions of solvents with various flow rates in different wavelengths by using a normal phase column to obtain the best separation and recovery results. As a result, a mobile phase consisting of n-hexane and ethyl acetate (75:25 v/v) at a constant flow rate of 0.8 mL min^?1 on the above column system at ambient temperature were found to be the optimal chromatographic condition for good separation and determination of ANO and DEL in samples. Multichromatograms for the concentration set containing ANO and DEL compounds in the concentration range of 50–400 ng mL^?1 were obtained by using a diode array detector (DAD) system at selected wavelength sets, 300 (A), 310 (B), 320 (C), 330 (D) and 340 (E). Three LC-chemometric approaches were applied to the multichromatographic data to construct chemometric calibrations. As an alternative method, traditional LC at single wavelength was used for the analysis of the related compounds in the plant extracts. All of the methods were validated by analyzing various synthetic ANO–DEL mixtures. After the above step, traditional and chemometric LC methods were applied to the real samples consisting of extracts from roots and aerial parts of S. resinosum. The results obtained by LC-chemometric approaches were compared to each other and with those obtained by traditional LC.     

Preliminary thermal characterization of natural resins from different botanical sources and geological environments

The preliminary studies on thermal behavior of differently aged natural resins from Russia (Khatanga), Dominican Republic (El Valle), Colombia and Poland (Jantar) were performed. Thermal stability and behavior under elevated temperature were investigated by thermogravimetry (TG) and differential scanning calorimetry (DSC), while the differences in the structure and composition by FT-IR spectroscopy. Analyzed resins show different thermal effects during heating suggesting that possible post-reactions and structural changes occurred. TG results indicated that Dominican, Russian and Colombian resins present relatively high thermal stability under air conditions in the range of 228–300 °C, whereas the mass loss of 5mass% at about 217 °C was observed for Baltic amber. During DSC experiments, the analyzed resins expose thermal events which make impossible determination of glass transition temperature in a raw sample. The results indicate that both TG and DSC cannot be considered as methods for age dating of natural resins and more advanced techniques should be applied. Careful analysis of FT-IR data in the carbonyl region may provide additional information about the composition and history of the natural resin.

     

Aqueous sol–gel synthesis and thermoanalytical study of the alkaline earth molybdate precursors

The preparation and characterization of the M′–Mo–O nitrate–tartrate (M′ = Mg, Ca, Sr, and Ba) gels, which were produced by the simple aqueous sol–gel method and calcined at 500, 600, 700, 800, 900, and 1,000 °C temperatures are reported. The crystalline alkaline earth metal molybdates (MgMoO₄, CaMoO₄, SrMoO₄, and BaMoO₄) and as-prepared M′–Mo–O nitrate–tartrate gels investigated by thermal analysis (TG/DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM). TG/DSC analysis showed the possible decomposition mechanism of synthesized gels. XRD studies allowed the identification of main types of crystalline structures in the MgMoO₄, CaMoO₄, SrMoO₄, and BaMoO₄ systems. Moreover, SEM analysis revealed the changes of surface morphology of the final compounds depending on annealing temperatures.     

Investigation of thermal behavior of Heliotropium indicum L. lyophilized extract by TG and DSC

Thermogravimetric (TG) techniques and differential scanning calorimetry (DSC) used for the study of pre-formulation or drug–adjuvant compatibility have been gaining importance in Brazil. These techniques are being used for the verification of possible interactions between drugs and adjuvants. Aiming at studying the behavior of a plant extract and its mixture with adjuvants, using these thermoanalytical techniques the plant species Heliotropium indicum L. was used. This plant which is originally from India and has been well acclimatized in Brazil has healing and anti-inflammatory properties. The methodology for obtaining the extract followed the Brazilian Pharmacopoeia methodology. And the incorporation of the extract with adjuvants was through binary mixtures (1:1 w/w). The TG and DSC curves were obtained under nitrogen atmosphere (25 mL min^?1) at a heating rate of 5 °C min^?1; TG tests were analyzed within a temperature range from 25 to 600 °C and DSC from 25 to 300 °C. The TG curves show good thermal stability of the extract and its mixtures with adjuvants up to 150 °C, except the propylene glycol (PLG). The DSC curves revealed an incompatibility of the extract with methylparaben and PLG mixture.     

Thermal Dehydration and Miscibility of PHEMA/PMAA Blends

Miscibility and dehydration of poly(2-hydroxyethyl methacrylate) and poly(methacrylic acid) (PHEMA/PMAA) blends were investigated by temperature modulated DSC (TMDSC), TG and solid-state ¹³C NMR methods. TMDSC spectra and ¹H spin-relaxation times showed that the blends are homogeneous on a scale of 5-10 nm for all compositions. From TG and ¹³C NMR, we elucidated that the mass loss of the blends at 300°C is ascribed to the dehydration between the hydroxyl group of PHEMA and the carboxyl group of PMAA. This revised version was published online in August 2006 with corrections to the Cover Date.     

Rapid calcination of ferrite Ni0.75Zn0.25Fe2O4 by microwave energy

Ferrites Ni_0.75Zn_0.25Fe₂O₄ were obtained by polymeric precursor method and calcined in a short time with microwave energy to assess the morphological and microstructural characteristics. Samples were calcined at 500, 650, 800, and 950 °C for 30 min in a microwave oven. The resulting powders were characterized by thermal analysis (TG/DSC), X-ray diffraction (XRD), Fourier transform infrared spectrometer, field-emission gun scanning electron microscope (FEG-SEM), and energy-dispersive X-ray spectroscopy. The XRD results showed the formation of single ferrite phase at temperature of 500 °C for 30 min. The FEG-SEM analysis showed agglomerated particles with formation of non-dense longitudinal plates, with interparticle porosity and agglomerated fine particles. The rapid calcination by microwave energy demonstrated satisfactory results in relatively low temperature of 500 °C for 30 min and appeared to be a promising technique for obtaining nickel–zinc ferrite powders.     

Investigation of clinoptilolite rich natural zeolites from Turkey: a combined XRF,TG/DTG,DTA and DSC study

Turkey clinoptilolite-rich tuffs from Gördes and Bigadiç regions of western of Anatolia and their exchanged forms (K⁺, Na⁺, Mg²⁺ and Ca²⁺) were characterized by TG/DTG-DTA, DSC and XRF methods and the surface areas were also determined for both tuffs. TG-DTG and DTA curves of all clinoptilolite samples were measured in the temperature range 30–1000 °C. All clinoptilolite samples had major, rapid mass losses between 30 and 200 °C, with slower and less significant mass losses at higher temperatures. The mass loss of the Natural-G is 9.54% while that of the Natural-B sample is 10.50%. Water content increases in the order of K < Na < Ca < Mg for Bigadiç clinoptilolite samples and in the following sequence K < Na < Mg < Ca for Gördes clinoptilolite samples. One mass loss step for all clinoptilolite samples was observed using differential scanning calorimeter (DSC) in the range of 30–550 °C.     

Fast detection of sildenafil in adulterated commercial products using differential scanning calorimetry

Adulteration of drugs is a serious issue and can have a great impact on human health. It is mainly done with the intention of boosting the effects of products. For many years, the enforcement officers in Malaysia have had difficulty deciding whether some products should be confiscated as they have not been able to produce fast reliable evidence of adulteration. For that reason, we explored the use of differential scanning calorimetry (DSC) as a potential fast detection method of commercial products marketed in Malaysia that may be adulterated. We confirmed the outcomes qualitatively with high pressure liquid chromatography. DSC was set at a heating rate of 10 °C min^?1 and within a temperature range of 100–250 °C with nitrogen as a purge gas at a flow rate of 20 mL min^?1 to analyse a sildenafil reference standard (RS), sildenafil tablets and sildenafil adulterated commercial products. Four sildenafil adulterated commercial products were analysed. Since the melting point of sildenafil in the mixture tended to shift, the presence of sildenafil in three of these adulterated commercial products was confirmed using the spiking method and was re-analysed using DSC. The re-analysed results indicated that the enthalphy of fusion (?H) and the resolution peak of sildenafil increased accordingly depending upon the amount of spiked sildenafil RS. Apart from these results, the DSC curves also showed different patterns for sildenafil RS and the mixtures. Therefore, we concluded that DSC can potentially be used to detect sildenafil in adulterated commercial products.     

Solid state of a new flavonoid derivative DA-6034

DA-6034 is a new synthetic flavonoid known to possess anti-inflammatory activity. The objective of this work was to investigate the existence of polymorphs and pseudopolymorphs of DA-6034. Six crystal forms, one hydrate form and five solvates, of DA-6034 have been isolated by recrystallization and characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TG), and powder X-ray diffractometry (PXRD). From the DSC and TG data it was confirmed that Form 1 is monohydrate; Form 2 is DMSO solvate; Form 3 is 1/2 DMSO solvate; Form 4 is 1/2 methyl ethyl ketone solvate; Form 5 is 1.5 H₂O, 1/2 acetic acid solvate; Form 6 is 1/2 H₂O, 1/4 butanol solvate. The PXRD patterns of the six crystal forms were different respectively. In the dissolution studies in pH 6.8 ± 0.05 buffer at 37 ± 0.5 °C, the solubility of solvates was higher than that of Form 1.     

Evaluation of thermal stability of enalapril maleate tablets using thermogravimetry and differential scanning calorimetry

Differential scanning calorimetry (DSC) and thermogravimetry (TG) were used in order to evaluate the thermal stability of an enalapril maleate formulation packaged in two types of packaging, polyvinyl chloride/aluminum blister and aluminum strip. Enalapril and the excipients employed in the formulation were also evaluated by TG and DSC. Tablets were analyzed before and after storage in an acclimatized room at 40 °C and relative humidity of 75 % for 90 days. The DSC and TG results were compared with the results of dosage of enalapril and related compounds obtained by high-performance liquid chromatography. These results indicate an occurrence of chemical interaction between enalapril maleate and the excipients during its storage. After storage, it was observed that the enalapril content reduced and the predominant degradation product was diketopiperazine for both types of packaging. The predominance of diketopiperazine could be related to the absence of sodium bicarbonate in the tablets, alkalinizing agent employed in the thermal stabilization of the drug.     

Thermal runaway reaction evaluation of benzoyl peroxide using calorimetric approaches

Benzoyl peroxide (BPO) has been used as initiator or medicine in the chemical industries. Several thermal runaway reactions, fires, and explosions have occurred in Taiwan due to its thermal reactivity and explosive properties. A serious accident was analyzed occurring at Fu-Kao Chemical Plant in Taiwan because of runaway reaction in a batch reactor including methyl acrylate (MA), acrylic acid (AA), and BPO. This accident resulted in one death and more than 100 injuries. Differential scanning calorimetry and thermogravimetry (TG) were used to investigate and calculate the thermal hazard and safety parameter of BPO. Finally, the effects of MA and AA mixed with BPO by DSC/TG were analyzed in this study. The T ₀ of BPO was 109 °C in this study. Therefore, the T ₀ of BPO/MA was calculated to be 105 °C by DSC. AA and MA were identified as catalyst for thermal decomposition of BPO.     

Guest-responsive covalent frameworks by the cross-linking of liquid-crystalline salts: tuning of lattice flexibility by the design of polymerizable units

Cross-linked polymers prepared by the in-situ polymerization of liquid-crystalline salts were found to work as solid-state hosts with a flexible framework. As a component of such hosts, four kinds of polymerizable amphiphilic carboxylic acids bearing alkyl chains with acryloyloxy (A), dienyl (D), and/or nonreactive (N) chain ends (monomeric carboxylic acids; M(AAA), M(ANA), M(DDD), and M(DND)) were used. The carboxylic acids were mixed with an equimolar amount of a template unit, (1R,2S)-norephedrine (guest amine; G(RS)), to form the corresponding salts. Every salt exhibited a rectangular columnar LC phase at room temperature, which was successfully polymerized by (60)Co γ-ray-induced polymerization without serious structural disordering to afford the salt of cross-linked carboxylic acid (polymeric carboxylic acid; P(AAA), P(ANA), P(DDD), and P(DND)) with G(RS) . Owing to the noncovalency of the interactions between the polymer framework P and the template G(RS), the cross-linked polymers could reversibly release and capture a meaningful amount of G(RS). In response to the desorption and adsorption of G(RS), the cross-linked polymers dramatically switched their nanoscale structural order. A systematic comparison of the polymers revealed that the choice of polymerizable groups has a significant influence on the properties of the resultant polymer frameworks as solid-state hosts. Among these polymers, P(DDD) was found to be an excellent solid-state host, in terms of guest-releasing/capturing ability, guest-recognition ability, durability to repetitive usage, and unique structural switching mode.