Thermal behavior of drugs

Data on the thermal stability of drugs was required to obtain information for handling, storage, shelf life and usage. In this study, the thermal stability of two nonsteroidal anti-inflammatory drugs (NSAIDs) was determined by differential scanning calorimetry (DSC) and simultaneous thermogravimetery/differential thermal analysis (TG/DTA) techniques. The results of TG analysis revealed that the main thermal degradation for the naproxen and celecoxib occurs in the temperature ranges of 196–300 and 245–359 °C, respectively. The TG/DTA analysis of compounds indicates that naproxen melts (at about 158.1 °C) before it decomposes. However, the thermal decomposition of the celecoxib started about 185 °C after its melting. The influence of the heating rate (5, 10, 15, and 20 °C min⁻¹) on the DSC behavior of the both drug samples was verified. The results showed that, as the heating rate was increased, decomposition temperatures of the compounds were increased. Also, the kinetic parameters such as activation energy and frequency factor for the compounds were obtained from the DSC data by non-isothermal methods proposed by ASTM E696 and Ozawa. Based on the values of activation energy obtained by various methods, the following order for the thermal stability was noticed: naproxen > celecoxib. Finally, the values of ΔS ^#, ΔH ^#, and ΔG ^# of their decomposition reaction were calculated.     

Thermal transitions and fat droplet stability in ice-cream mixmodel systems

We studied thermal transitions and physical stability of oil-in-water emulsions containing different milk fat compositions, arising from anhydrous milk fat alone (AMF) or in mixture (2:1 mass ratio) with a high melting temperature (AMF–HMT) or a low melting temperature (AMF–LMT) fraction. Changes in thermal transitions in bulk fat and emulsion samples were monitored by differential scanning calorimetry (DSC) under controlled cooling and reheating cycles performed between 50 and –45°C (5°C min^–1). Comparison between bulk fat samples and emulsions indicated similar values of melting completion temperature, whereas initial temperature of fat crystallization (T_onset) seemed to be differently affected by storage temperature depending on triacylglycerols (TAG) composition. After storage at 4°C, T_onset values were very similar for emulsified and non-emulsified AMF–HMT blend, whereas they were lower (by approx. 6°C) for emulsions containing AMF or mixture of AMF–LMT fraction. After storage at –30°C, T_onset values of re-crystallization were higher in emulsion samples than in bulk fat blends, whatever the TAG fat composition. Light scattering measurements and fluorescence microscopic observations indicated differences in fat droplet aggregation-coalescence under freeze-thaw procedure, depending on emulsion fat composition. It appeared that under quiescent freezing, emulsion containing AMF–LMT fraction was much less resistant to fat droplet aggregation-coalescence than emulsions containing AMF or AMF–HMT fraction. Our results indicated the role of fat droplet liquid-solid content on emulsion stability.     

Thermal Stability and Molecular Ordering of Organic Semiconductor Monolayers: Effect of an Anchor Group

The thermal stability and molecular order in monolayers of two organic semiconductors, PBI‐PA and PBI‐alkyl, based on perylene derivatives with an identical molecular structure except for an anchor group for attachment to the substrate in PBI‐PA, are reported. In situ X‐ray reflectivity measurements are used to follow the stability of these monolayers in terms of order and thickness as temperature is increased. Films have thicknesses corresponding approximately to the length of one molecule; molecules stand upright on the substrate with a defined structure. PBI‐PA monolayers have a high degree of order at room temperature and a stable film exists up to 250 °C, but decomposes rapidly above 300 °C. In contrast, stable physisorbed PBI‐alkyl monolayers only exist up to 100 °C. Above the bulk melting point at 200 °C no more order exists. The results encourage using anchor groups in monolayers for various applications as it allows enhanced stability at the interface with the substrate.     

Non-isothermal kinetic study of the thermal decomposition of diaminoglyoxime and diaminofurazan

Data on the thermal stability of organic materials such as diaminofurazan (DAF) and diaminoglyoxime (DAG) was required in order to obtain safety information for handling, storage and use. These compounds have been shown to be a useful intermediate for the preparation of energetic compounds. In the present study, the thermal stability of the DAF and DAG was determined by differential scanning calorimetery (DSC) and simultaneous thermogravimetery-differential thermal analysis (TG-DTA) techniques. The results of TG analysis revealed that the main thermal degradation for the DAF and DAG occurs in the temperature ranges of 230–275°C and 180–230°C, respectively. On the other hand, the TG-DTA analysis of compounds indicates that DAF melts (at about 182°C) before it decomposes. However, the thermal decomposition of the DAG started simultaneously with its melting. The influence of the heating rate (5, 10, 15 and 20°C min⁻¹) on the DSC behaviour of the compounds was verified. The results showed that, as the heating rate was increased, decomposition temperatures of the compounds were increased. Also, the kinetic parameters such as activation energy and frequency factor for the compounds were obtained from the DSC data by non-isothermal methods proposed by ASTM E698 and Ozawa. Based on the values of activation energy obtained by ASTM and Ozawa methods, the following order in the thermal stability was noticed: DAF>DAG.     

Research of thermal decomposition kinetic characteristic of emulsion explosive base containing Fe and Mn elements

The kinetic characteristic of thermal decomposition of the Emulsion Explosive Base Containing Fe and Mn elements (EEBCFM) which was used to prepare nano-MnFe₂O₄ particles via detonation method was investigated by means of non-isothermal DSC and TG methods at various heating rates of 2.5, 5 and 7.5°C min⁻¹respectively under the atmosphere of dynamic air from room temperature to 400°C. The results indicated that the EEBCFM was sensitive to temperature, especially to heating rate and could decompose at the temperature up to 60°C. The maximum speed of decomposition (dα/dT)_m at the heating rate of 5 and 7.5°C min⁻¹ was more than 10 times of that at 2.5°C min⁻¹ and nearly 10 times of that of the second-category coal mine permitted commercial emulsion explosive (SCPCEE). The plenty of metal ions could seriously reduce the thermal stability of emulsion explosive, and the decomposition reaction in the conversion degree range of 0.0∼0.6 was most probably controlled by nucleation and growth mechanism and the mechanism function could be described with Avrami-Erofeev equation with n=2. When the fractional extent of reaction α>0.6, the combustion of oil phase primarily controlled the decomposition reaction.     

Polybenzimidazoles tethered with N‐phenyl 1,2,4‐triazole units as polymer electrolytes for fuel cells

Polybenzimidazole (PBI) polymers tethered with N‐phenyl 1,2,4‐triazole (NPT) groups were prepared from a newly synthesized aromatic diacid, 3′‐(4‐phenyl‐4H‐1,2,4‐triazole‐3,5‐diyl) dibenzoic acid (PTDBA). The obtained polymers show superior thermal and chemical stability and good solubility in many aprotic solvents. The inherent viscosities of all polymers were around 1 dL/g. They exhibit high thermal stability with initial decomposition temperature ranging from 515 to 530 °C, high glass transition temperature ranging from 375 to 410 °C, and good mechanical properties with tensile stress in the range of 66–98 MPa and modulus 1897–2600 MPa. XRD analysis indicates that these polymers are amorphous in nature. Physicochemical properties such as water and phosphoric acid‐uptake, oxidative stability, and proton conductivity of membranes of these polymers have also been determined. The proton conductivity ranged from 4.7 × 10^?3 to 1.8 × 10^?2 S cm^?1 at 175 °C in dry conditions. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2289–2303, 2009     

Thermal characterization of antimicrobial drug ornidazole and its compatibility in a solid pharmaceutical product

The ornidazole drug substance presents melt at approximately 90 °C (∆T = 85–98 °C), which is critical for its use on pharmaceutical manufacturing process. This work aimed the thermal characterization of ornidazole raw-material synthesized by three different manufacturers from India, China, and Italy, using the thermoanalytical techniques of DTA, DSC, and TG, besides the verification of its stability and compatibility as a solid pharmaceutical product by the analysis of its binary mixtures (BM) with excipients and a tablet formulation. The characterization includes the thermal decomposition kinetic investigation by Ozawa model using Arrhenius equation and drug purity determination by Van’t Hoff equation. The DSC purity determination and precision were compared with results from UV–Vis spectrophotometric and liquid chromatography, showing an adequate correlation before being recommended as a general method for purity assay. The drug raw-materials presented similar quality and zero-order kinetic behavior, besides showing differences on thermal stability. The drug presented compatibility with the tested excipients since the BM studied presented melting at the same temperature range as the drug and a decomposition temperature similar to the drug for two of the BM, and at a higher temperature for the others three of the BM evaluated, which presented excipients with higher molecular structure, capable of spatial coating on the small drug molecule promoting a physical interaction pharmaceutical acceptable. The tablet was processed by wet granulation and compressed under normal conditions of pressure and temperature, maintaining the physical properties of solid drug approving the manufacturing process used. In this study, the thermal analysis was used with success as an alternative method to characterize, quantify, and perform a preformulation study.     

Thermal Measurements on Poly[2,2'-(m-phenylene)-5,5'-bibenzimidazole] Fibers

Fibers drawn form poly[2,2'-(m-phenylene)-5,5'-bibenzimidazole] (PBI) were studied by DSC and DMA. PBI is a high temperature polymer T _g is between 387 and450°C depending on the measurement technique used. The as-spun fiber is free of orientation. The oriented fiber exhibits considerable dependence on whether the DSC measurements were carried out in free-to-shrink or fixed-length modes. The β-relaxation is at 290°C, and was associated with loss of water. The γ-transition at 20°C was not identified, while theδ-transition at –90°C seems to correspond to rotation of the m-phenylene ring. This revised version was published online in July 2006 with corrections to the Cover Date.     

Thermochemical and thermal analysis on N-(p-methylphenyl)-N'-(2-pyridyl)urea

Low temperature heat capacities of N-(p-methylphenyl)-N'-(2-pyridyl)urea were determined by adiabatic calorimetry method in the temperature range from 80 to 370 K. It was found that there was not any heat anomaly in this temperature region. Based on the experimental data, some thermodynamic function results were obtained. Thermal stability and decomposition characteristics analysis of N-(p-methylphenyl)-N'-(2-pyridyl)urea were carried out by DSC and TG. The results indicated that N-(p-methylphenyl)-N'-(2-pyridyl)urea started to melt at ca. 426 K (153°C) and the melting peak located at 447.01 K (173.86°C). The melting enthalpy was 204.445 kJ mol^-1 (899.6 J g^-1). The decomposition peak of N-(p-methylphenyl)-N'-(2-pyridyl)urea was found at 499.26 K (226.11°C) from DSC curve. This result was similar with that from TG and DTG experiment, in which the mass loss peak was determined as 500.4 K (227.2°C). This revised version was published online in August 2006 with corrections to the Cover Date.     

Characterization of Nitro-Substituted Polybenzimidazole Synthesized by the Reaction with Nitric Acid

Abstract

Nitro-substituted poly[2,2′-(m-phenylene)-5,5′-bibenzimidazole]s (PBIs) were synthesized by the reaction of PBI with nitric acid in sulfuric acid under various conditions. The number of nitro groups substituted on the aromatic ring of PBI per polymeric unit varied from 1.44 to 3.55 according to the reaction conditions. An increase in reaction temperature and concentration of the nitric acid increased the degree of substitution. The inherent viscosity of the substituted polymer increased as the reaction temperature decreased. When the reaction temperature was 30°C, the inherent viscosity of the polymer increased as the concentration of nitric acid increased. The nitro-substituted PBI exhibited polyelectrolyte behavior in formic acid. The nitro groups substituted on PBI were dissociated when the polymer was heated to 450°C, displaying exothermic behavior, and the decomposition of polymer was proportional to its nitro group content. All nitro-substituted PBIs showed better solubilities in polar aprotic and acidic solvents, such as dimethylacetamide, dimethylsulfoxide, dimethylformamide, N-methylpyrrolidone, formic acid, sulfuric acid, and trifluoromethanesulfonic acid.     

Thermal behavior of loratadine

Simultaneous thermogravimetry (TG) and differential thermal analysis (DTA) techniques were used for the characterization the thermal degradation of loratadine, ethyl-4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidine)-1-piperidinecarboxylate. TG analysis revealed that the thermal decomposition occurs in one step in the 200–400°C range in nitrogen atmosphere. DTA and DSC curves showed that loratadine melts before the decomposition and the decomposition products are volatile in nitrogen. In air the decomposition follows very similar profile up to 300°C, but two exothermic events are observed in the 170–680°C temperature range. Flynn–Wall–Ozawa method was used for the solid-state kinetic analysis of loratadine thermal decomposition. The calculated activation energy (E _a) was 91±1 kJ mol^–1 for α between 0.02 and 0.2, where the mass loss is mainly due to the decomposition than to the evaporation of the decomposition products.     

Synthesis and thermal decomposition of ditetrazol-5-ylamine

Ditetrazol-5-ylamine (DTA) was synthesized from cyanuric chloride in four steps. The thermal decomposition of DTA in the solid state was studied by thermogravimetry, volumetry, mass spectrometry, IR spectroscopy, and calorimetry. Under isothermal conditions at 200–242 °C, thermal decomposition obeys the first order autocatalytic kinetics. The kinetic and activation parameters of DTA decomposition were determined. The composition of gaseous reaction products and the structure of condensed residue were studied. The thermal effect of thermal DTA decomposition is 281.4 kJ mol⁻¹. The nitrogen content in a mixture of gaseous products formed by the reaction in a temperature interval of 200–242 °C exceeds 97 vol.%. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1660–1664, July, 2005.     

The highly crosslinked dimethacrylic/divinylbenzene copolymers

The thermal stability of the ionic liquids (ILs) 1-n-butyl-3-methylimidazolium bromide, [BMIM]Br, and 1-n-octyl-3-methylimidazolium bromide, [OMIM]Br, was evaluated through thermogravimetry (TG). Long-term isothermal TG studies revealed that both of these ILs exhibit appreciable decomposition even at temperatures significantly lower than the onset decomposition temperature, previously determined from fast scan TG experiments. The long-term TG studies of both the ILs showed linear mass loss as a function of time at each temperature of 10 °C interval in the range 533–573 K over a period of 10 h. The kinetics of isothermal decomposition of ILs was analyzed using pseudo-zero-order rate expression. The activation energies for the isothermal decomposition of [BMIM]Br and [OMIM]Br under nitrogen atmosphere are 219.86 and 212.50 kJ mol⁻¹, respectively. The moisture absorption kinetics of these ILs at 25 °C and 30% relative humidity (RH) and at 85 °C and 85% RH were also studied. Water uptake of ILs exposed at 25 °C/30%RH follows a simple saturation behavior in agreement with Weibull model while that at 85 °C/85%RH fortuitously fit into the Henderson–Pabis model.     

TGA–MS degradation studies of some new aliphatic–aromatic polybenzimidazoles

The degradation of a series of polybenzimidazoles containing metylene groups in the chain was studied by TGA and MS. On heating the polymer derived from m-phenylenediacetic acid and 3,3′-diaminobenzidine to about 560°C in argon, partial fast decomposition into a solid sublimate was observed. The sublimate consisted of a mixture of fractions derived from the breaking of the chain at the methylene bonds. These methylene groups can be preoxidized at 250°C to carbonyl groups, eliminating thereby this mode of decomposition. At temperature higher than 560°C, gaseous products similar to those of the corresponding all-aromatic PBI are obtained.     

Thermal decomposition of the composite hydrotalcites of iowaite and woodallite

The thermal stability and thermal decomposition pathways for synthesized composite iowaite/woodallite have been determined using thermogravimetry analysis in conjunction with evolved gas mass spectrometry. Dehydration of the hydrotalcites occurred over a range of 56–70°C. The first dehydroxylation step occurred at around 255°C and, with the substitution of more iron(III) for chromium(III) this temperature increased to an upper limit of 312°C. This trend was observed throughout all decomposition steps. The release of carbonate ions as carbon dioxide gas initialised at just above 300°C and was always accompanied by loss of hydroxyl units as water molecules. The initial loss of the anion in this case the chloride ion was consistently observed to occur at about 450°C with final traces evolved at 535 to 780°C depending of the Fe:Cr ratio and was detected as HCl (m/z=36). Thus for this to occur, hydroxyl units must have been retained in the structure at temperatures upwards of 750°C. Experimentally it was found difficult to keep CO₂ from reacting with the compounds and in this way the synthesized iowaite-woodallite series somewhat resembled the natural minerals.     

Rigid-rod liquid crystalline polyesters based on n-alkoxyterephthalic acid and 4,4′-dihydroxybiphenyl

The synthesis and the characterization of a set of polymers obtained by polycondensation of n-alkoxyterephthalic acid (n = 1, 3, 5, 7) and 4,4′-dihydroxybiphenyl are reported. The n-alkoxy insertion promotes the processability of the material by lowering the melting temperature. All polymers show the nematic phase at about 300°C, almost independently of the length of lateral substituent. The isotropization is not observed up to 450°C, where thermal decomposition occurs. The temperature of glass transition decreases with increasing n, ranging from 170°C (n = 5) to 220°C (n = 1). © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 263–267, 1998     

New high temperature polymers. I. Wholly aromatic ordered copolyamides

Wholly aromatic ordered copolyamides of unusually high thermal stability were prepared by the condensation of aromatic diacid chlorides with symmetrical diamines containing preformed aromatic amide units in an ordered arrangement. The preservation of order in the condensation step was assured by using interfacial or solution polymerization techniques at temperatures below 50°C. Each polymer contains units derived from aminobenzoic acids, arylene diamines, and arylene diacids. By use of para- and meta- phenylene units, eight different polymers are possible; all were prepared. Differential thermal analyses and thermogravimetric analyses showed these polymers to have melting points or decomposition temperatures in a range from 410°C. for the all-meta polymer to 555°C. for the all-para one. Substitution of the internal N-hydrogens of the diamines with methyl groups or phenyl groups leads to additional ordered copolymers. Several were prepared, but their melting points were much lower than those of the parent polymers limiting their usefulness in high temperature applications. Tough pliable films were prepared from all eight unsubstituted polymers, and crystalline fibers with tenacities of ca. 6 g./den. were prepared from three of the polymers. The properties of the fibers were retained to a high degree even when determined at temperatures up to 400°C. Fibers aged at 300°C. for extended periods of time showed remarkable retention of fiber properties.     

Thermal decomposition of solid state poly(β-L-malic acid)

Thermal decomposition process of solid state poly(β -L-malic acid) was traced by DSC combined with FT-IR. Melting temperature of this partially crystallized polymer was detected at 46-60°C. The thermal decomposition initiated at ca 185°C accompanied by an evolution of gaseous products. In contrast to the cleavage reaction in the aqueous polymer solutions which gives L-malic acid and corresponding dimer of L-malic acid, the solid state poly(β -L-malic acid) decomposed at above the decomposition temperature giving not the constituent L-malic acid but fumaric acid at the first stage of the reaction then, maleic and maleic anhydride. This revised version was published online in July 2006 with corrections to the Cover Date.     

Polymerization of 2-azabicyclo[2,2,1]heptan-3-one and its copolymerization with 2-pyrrolidone

The anionic polymerization of a bridged bicyclic lactam, 2-azabicyclo[2,2,1]heptan-3-one (ABHO), was carried out in bulk and in solution under various reaction conditions. In general bulk polymerization of ABHO was superior to solution polymerization in conversion and degree of polymerization. The resulting polymer exhibited good thermal stability at temperatures up to 300°C. The melting point and decomposition temperature of this polyamide, poly(cyclopentane-1,3-diyliminocarbonyl), were about 307 and 335°C, respectively. Copolymerization of ABHO with 2-pyrrolidone was also made at 30°C and a varying weight percentage of ABHO with potassium pyrrolidonate as catalyst and CS₂ as activator. Copolyamides that contained 15 w % of ABHO decomposed at a temperature higher than the melting point by almost 30°C. Thus the thermal stability of copolymers compared with that of nylon-4, was greatly improved. Moisture sorptions of homopolymers and copolymers were always larger than those of other polyamides (nylon 4 and 6) at any relative humidity. Tenacity and elongation at the break of melt-spun fibers obtained from copolyamides that contained 15 w % of ABHO without the drawing and annealing process were 1.25 g/den and 13.1%, respectively.     

Characterization and thermal stability of PMR polyimides using 7-oxa-bicyclo[2,2,1]hept-5-ene-2, 3-dicarboxylic anhydride as end caps

An anhydride monomer containing ether oxide bridge,7-oxa-bicyclo[2,2,1]hept-5-ene-2,3-dicarboxylic anhydride (ONA),was successfully synthesized by Diels-Alder reaction of furan and maleic anhydride.The ONA was also studied as an end-cap for the polymerization of monomer reactant(PMR) type polyimides.Three molecular weight levels of the ONA end-capped PMR resins were evaluated.The effects of process conditions of these novel PMR resins on thermal and mechanical properties were investigated.It was demonstrated that the imidized prepolymers using the end-cap have good processability,and the cured polyimide specimens exhibited good thermal stability.The initial decomposition temperature, T_d(ca.580℃) and glass transition temperature,T_g(330℃) of the novel resin(PI-20),prepared under optimum process conditions,compare favorably with the T_d(ca.620℃) and T_g(ca.348℃) of the state-of-the-art resin(PI’-20),respectively.