Estudo de compatibilidade e estabilidade térmica do ácido retinóico e hidroquinona por termogravimetria

Retinoic acid (RA) and hydroquinone (HQ) assets are widely used in pharmaceutical and cosmetic formulations, for having depigmenting properties and are largely produced in drugstores. To assist in the development of formulations containing the active RA and HQ National Forms of Brazilian Pharmacopoeia (2005 and 2012 ) proposes formulations with different excipients such as cetyl alcohol (AC), cetostearyl alcohol (ACT), methylparaben (MTP), propyl paraben ( PPB), glycerin (GLY), dipropylene glycol (DPG), imidazolidinil urea ( IMD ), cyclomethicone (CCM ), butylated hydroxytoluene (BHT), octyl stearate (ETO), EDTA, decil oleate (ODC) and hydroxipropymethyl celullose (HPMC). One of the difficulties found in most cosmetic formulations is the large number of incompatibilities between the components of the formulations, so the aim this study was to evaluate thermal stability and interactions between these active pharmaceutical ingredients and excipients. The depigmenting agents were analyzed by DSC and TG and excipients were analyzed by TG. The dynamic thermogravimetric curves were obtained on a SHIMADZU thermobalance, model DTG-60, using an alumina crucible, at the heating rate of 10ºC min-1, in the temperature range of 25-900 ºC, under an atmosphere of nitrogen at 50 mL min-1. The DSC curves were obtained using Shimadzu calorimeter, model DSC-60, using aluminum crucible, at the heating rate of 10ºC min-1, in the temperature range of 25-400ºC. The thermogravimetric and calorimetric curves were analyzed using TASYS software SHIMADZU. In this study no were found interactions between AR and the following excipients: MTP, PPB, IMD, ODC, EDTA, CCM, ETO, HPMC. However, were found interactions with the following excipients: AC, ACT, BHT, GLI and DPG. For HQ were found interactions with IMD and DPG. Interactions remained even changing proportions of the mixtures and the ternary. Thus, the studies conducted with excipients of National Formulary from 2005 and 2012 showed that these new excipients do not interact by thermogravimetry with the active pharmaceutical ingredients of this study

Aplicação da termogravimetria na determinação do teor de ferro em comprimidos: um estudo comparativo com a espectrofotometria

This study used the Thermogravimetry (TG) and molecular absorption spectroscopy in UV-visible region to determine the iron content in herbal medicinal ferrous sulfate used in the treatment of iron deficiency anemia. The samples were characterized by IR, UV, TG / DTG, DTA, DSC and XRD. The thermoanalytical techniques evaluated the thermal stability and physicochemical events and showed that the excipients interfere in the decomposition of the active ingredients. The results of thermogravimetry showed that the decomposition temperature of the active principle Fe2(SO4)3 (T = 602 °C) is higher as compared to samples of tablets (566 586 °C). In the DTA and DSC curves were observed exothermic and endo events for samples of medicines and active analysis. The infrared spectra identified key functional groups exist in all samples of active ingredients, excipients and compressed studied, such as symmetric and asymmetric stretching of OH, CH, S=O. The analysis by X-ray diffraction showed that all samples had crystallinity and the final residue showed peaks indicating the presence of silicon dioxide, titanium dioxide and talc that are excipients contained in pharmaceutical formulations in addition to iron oxide. The results obtained by TG to determine the iron content of the studied drugs showed a variance when compared with those obtained by theoretical and UV-visible, probably due to formation of a mixture of Fe2O3 and Fe2(SO4)3. In one tablet was obtained FE content of 15.7 % and 20.6 % for TG by UV-visible, the sample EF 2 was obtained as a percentage of 15.4 % and 21.0 % for TG by UV-visible . In the third SF samples were obtained a content of 16.1 % and 25.5 % in TG by UV-visible, and SF 4 in the percentage of TG was 16.7 % and 14.3 % UV-visible

Aplicabilidade da voltametria de pulso diferencial na quantificação de ácido fólico e ácido oxálico: um método comparativo

The development of more selective and sensitive analytical methods is of great importance in different areas of knowledge, covering, for example, food, biotechnological, environmental and pharmaceutical sectors. The study aimed to employ the technique electroanalytical differential pulse voltammetry (DPV) as an innovative and promising alternative for identification and quantification of organic compounds. The organic compounds were investigated in this study oxalic acid (OA) and folic acid (FA). The electrochemical oxidation of oxalic acid has been extensively studied as a model reaction in the boundary between the organic and inorganic electrochemistry. Since the AF, an essential vitamin for cell multiplication in all tissues, which is essential for DNA synthesis. The AF has been investigated using analytical techniques, liquid chromatography and molecular absorption spectrophotometry. The results obtained during the experimental procedure indicated that the process of electrochemical oxidation of oxalic acid is strongly dependent on the nature of the anode material and the oxidation mechanism, which affects their detection. Efficient removal was observed in Ti/PbO2 anodes, graphite, BDD and Pt 90, 85, 80 and 78% respectively. It was also shown that the DPV employing glassy carbon electrode offers a fast, simple, reliable and economical way to determine the AO during the process of electrochemical oxidation. Furthermore, electroanalytical methods are more expensive than commonly used chromatographic analysis and other instrumental methods involving toxic reagents and higher cost. Compared with the classical method of titration and DPV could be a good fit, confidence intervals and detection limits confirming the applicability of electroanalytical technique for monitoring the degradation of oxalic acid. For the study of AF was investigated the electrocatalytic activity of the carbon paste electrode for identification and quantification in pharmaceutical formulations by applying the DPV. The results obtained during the experimental procedure showed an irreversible oxidation peak at 9.1 V characteristic of FA. The carbon paste sensor showed low detection limit of 5.683×10−8 mol L-1 reducing matrix effects. The spectrophotometric analysis showed lower concentrations of HF compared with those obtained by HPLC and DPV. The levels of AF were obtained according to the methodology proposed by the Brazilian Pharmacopoeia. The electroanalytical method (DPV) proposed is cheaper than GC analysis commonly used by the pharmaceutical industry. The results demonstrated the potential of these electroanalytical techniques for future applications in environmental, chemical and biological sensors

Trissoralen um medicamento de baixa dosagem: estudos termoanalíticos da compatibilidade do fármaco-excipientes e determinação de parâmetros de qualidade para cápsulas magistrais

The trioxsalen (Tri) is a low-dose drug used in the treatment of psoriasis and other skin diseases. The aim of the study was applying the thermal analysis and complementary techniques for characterization, evaluation of the trioxsalen stability and components of manipulated pharmaceutical formulations. The thermal behavior of the Tri by TG/DTG-DTA in dynamic atmosphere of synthetic air and nitrogen showed the same profile with a melting peak followed by a volatilization-related event. From the curves TG / DTG is observed a single stage of mass loss. By heating the drug in the stove at temperatures of 80, 240 and 260 °C, it had no change in chemical structure through the techniques of XRD, HPLC, MIR, OM and SEM. From the non-isothermal and isothermal TG kinetic studies was possible to calculate the activation energy and reaction order for the Tri. The drug showed good thermal stability. Studies on drug-excipient compatibility showed interaction of trissoralen with sodium lauryl sulfate 1:1. There was no interaction with aerosol, pregelatinized starch, sodium starch glycolate, cellulose, croscarmellose sodium, magnesium stearate, lactose and mannitol.The characterization of three trioxsalen formulations at concentrations of 2.5, 5, 7.5, 10, 12.5 and 15 mg was performed by DSC, TG / DTG, XRD, NIR and MIR. The PCA classification method based on spectral data from the NIR and MIR of trissoralen formulations allows successful differentiation into three groups. The formulation 3 was the one that best showed analytical profile with the following composition of aerosil excipients, pre-gelatinized starch and cellulose. The activation energy of the volatilization process of the drug was determined in binary mixtures and formulation 3 through fitting and isoconversional methods. The binary mixture with sodium starch glycolate and lactose showed differences in kinetic parameters compared to the drug isolated. The thermoanalytical techniques (DSC and TG / DTG) were shown to be promising methodologies for quantifying trioxsalen obtained by the linearity, selectivity, no use solvents, without sample preparation, speed and practicality.

Obtenção de extratos da Opuntia fícus-indica L. Mill e suas aplicações em formulações cosméticas: avaliação in vivo do sensorial e da eficácia hidratante

Opuntia fícus - indica (L.) Mill is a cactacea presents in the Caatinga ecosystem and shows in its chemical c omposition flavonoids, galacturonic acid and sugars. Different hydroglicolic (EHG001 and EHG002) and hydroethanolic subsequently lyophilized (EHE001 and EHE002) extracts were developed. The EHE002 had his preliminary phytochemical composition investigated by thin layer chromatography (TLC) and we observed the predominance of flavonoids. Different formulations were prepared as emulsions with Sodium Polyacrylate (and) Hydrogenated Polydecene (and) Trideceth - 6 (Rapithix® A60), and Polyacrylamide (and) C13 - 14 I soparaffin (and) Laureth - 7 (Sepigel® 305), and gel with Sodium Polyacrylate (Rapithix® A100). The sensorial evaluation was conducted by check - all - that - apply method. There were no significant differences between the scores assigned to the formulations, howe ver, we noted a preference for those formulated with 1,5% of Rapithix® A100 and 3,0% of Sepigel® 305. These and the formulation with 3% Rapithix® A60 were tested for preliminary and accelerated stability. In accelerated stability study, samples were stored at different temperatures for 90 days. Organoleptic characteristics, the pH values and rheological behavior were assessed. T he emulsions formulated with 3,0% of Sepigel® 305 and 1,5% of Rapithix® A60 w ere stable with pseudoplastic and thixotropic behavior . The moisturizing clinical efficacy of the emulsions containing 3,0% of Sepigel® 305 containing 1 and 3% of EHG001 was performed using the capacitance method (Corneometer®) and transepidermal water lost – TEWL evaluation ( Tewameter®). The results showed t hat the formulation with 3% of EHG001 increased the skin moisturizing against the vehicle and the extractor solvent formulation after five hours. The formulations containing 1 and 3% of EHG001 increased skin barrier effect by reducing transepidermal water loss up to four hours after application.

Desenvolvimento de formulações para produção de grés porcelanato a partir de matérias-primas da região da bacia do Parnaíba

Brazil is a great ceramic raw materials productor because of the its big number of clay deposits, in various areas of the ceramic industry. Although, the majority of the natural reservations are unknown or not studied yet, so there is no scientific technical dates that can guide their usage and industrial application, as well as the racional and optimazed way of usage by the industrial sector. The state of Maranhão has a gigant mineral wealth as esmectite, bentonite, kaolin, clays, feldspates, marine salt, iron and others, but produce only products with small agregated value compared to the porcelanato, one of the most expensives ceramic cover tiles, the reason for that is the low water absorption (lower than 0,5%), beside present amazing tecnicals features, like mechanical resistence. The main objective of the work is to do the characterization of four clays, with the finallity of find an application by the results and develop formulations to produce porcelanato using these raw materials from Timon-MA. For this were made the raw materials characterization using X ray fluorecence; X ray diffraction; Differencial thermal analysis; Dilatometric analysis and Tecnological properties, planing three formulations that were sinterized at six different temperatures: 1150, 1170, 1190, 1210, 1230 and 1250ºC for 7 minutes. After the sinteratization, the samples were submitted to tension resistance analysis. Were attained two formulations with the requested properties to produce porcelanato

Estudo da incorporação de cascalho proveniente da perfuração de poços de petróleo em formulações para tijolos de solo-cimento

The present work is to study the characteristics and technological properties of soil-cement bricks made from binary and ternary mixtures of Portland cement, sand, water, with or without addition of gravel from the drilling of oil wells, which could be used by industry, aiming to improve its performance and reduce cost by using the residue and, consequently, increasing its useful life. The soil-cement bricks are one of the alternatives to masonry construction. These elements, after a short curing period, provide compressive strength similar to that of solid bricks and ceramic blocks, and the higher the resistance the higher the amount of cement used. We used the soil from the city of São José do Mipibu / RN, the banks of the River Baldun, cement CPIIZ-32 and residue of drill cuttings from oil wells drilling onshore wells in the town of Mossley, RN, provided Petrobras. To determine the optimum mix, we studied the inclusion of different residues (100%, 80%, 70%, 60% and 50%) where 15 bodies were made of the test piece. The assessment was made of bricks made from simple compression tests, mass loss by immersion and water absorption. The experimental results proved the efficiency and high utilization of the waste from the drilling of oil wells, making the brick-cement-soil residue with a higher strength and lower water absorption. The best result in terms of mechanical strength and water absorption for the ternary mixture was 10% soil, 14% cement and 80% residue. In terms of binary mixtures, we obtained the best result for the mix-cement residue, which was 14% cement incorporated in the residue

Avaliação da potencialidade dos resíduos de gesso de revestimento incorporados em formulações de massas cerâmicas

In building, during the implementation process of major or even minor works, there is a considerable waste of plaster in the steps of coating, making it is a negative factor because of the loss of these processes constructive remains incorporated into buildings, as component, whose final dimensions are higher than those projected. Another negative factor is the disposal of waste gypsum in inappropriate places, thus contributing to the degradation of environmental quality, due to the leaching of this waste and may trigger the formation of sulfuric acid. Therefore, based on this picture, processing and reuse of waste coating, combined with the ceramics industry, which is a strong potential in the reuse of certain types of waste, promote mutual benefits. Thus the overall objective of this work is to conduct a search with scientific and technological aspects, to determine the effect of the incorporation of the residue of plaster for coating, from the building, the formulation of bodies for red ceramic. The residue of plaster coating was collected and characterized. They were also selected raw materials of two ceramic poles of the state of Rio Grande do Norte and formulations have been made with the intention of obtaining those with the best physical and mechanical properties, the residue was added the percentage of 5%, 10%, 15%, 20%, 25% and 30%, in the best formulation of ceramic industry 1 and, according the properties analyses, 5%, 10% and 15% as the best results of ceramic industry 2. The samples were sintered at temperatures of 850 ºC, 950 °C and 1050 °C, the heating rate of 5 ºC / min with isotherm of two hours. They were submitted to testing technology, such as lineal shrinkage, water absorption, apparent porosity, apparent density and bending resistence. The residue incorporation best results in the formulations of mass in red ceramic, were observed between the temperatures of 850 ºC and 950 ºC, in those formulations that have illite clays and medium plastic in their composition, in the range of 0% to 15% residue incorporated

Efeito da adição de feldspato e/ou resíduo de caulin em formulações à base de argila ilítica

The red pottery industry in Piauí state is well developed and stands out at the national context for the technical quality of its products. The floor and wall tile industry, however, is little developed since the state has only one company that produces red clay-based ceramic tiles. This thesis aims at using the predominantly illitic basic mass of the above mentioned industry, with the addition of feldspar and/or kaolin residue in order to obtain products of higher technical quality. Kaolin residue consists basically of kaolinite, muscovite mica and quartz; the feldspar used was potassic. In this experiment, basic mass (MB) was used for experimental control and fifteen formulations codified as follows: F2, F4, F8, F16, F32, FR2, FR4, FR8, FR16, FR32, R2, R4, R8, R16 and R32. All raw materials were dry-milled, classified, formulated and then humidified to 10% water. Thereafter, test samples were produced by unixial pressing process in a rectangular steel matrix (60.0 x 20.0 x 5.0) mm3 at (25 MPa). They were fired at four temperatures: 1080°C, 1120°C, 1160°C, with a heating rate of 10°C/min during up to 10 min in an electric oven, and the last one in an industrial oven with a peak of 1140°C, aim ing to confirm the results found in laboratory and, finally, technological tests were performed: MEA, RL, AA, PA, TRF and PF. The results revealed that the residue under study can be considered a raw material with large potential in the industry of red clay-based ceramic tiles, since the results found both in laboratory and in the industry have shown that the test samples produced from the formulations with up to 4% feldspar and those produced with up to 8% feldspar and residue permitted a reduction in the water absorption rate and an increase in the mechanical resistance while those samples produced with up to 4% residue had an increase in the mechanical resistance when compared to those produced from the basic mass and that the formulation with 2% feldspar and residue presented the best technological properties, lowering the sintering temperature down to 1120°C

Uso de resíduo e de minerais de pegmatito da região do seridó RN e de argilas portuguesas em formulações de grês porcelanato

In the State Rio Grande do Norte, Brazil, the most significant deposits of minerals in the production of granite and pegmatite are Seridó region. Municipalities of Parelhas and Equador are the main responsible for the production of feldspar, quartz, kaolin and granite. The ceramic industries are always in search of competitiveness by investing in new products or improving existing techniques. The stoneware is a type of pottery that stands in the market because it presents technical and aesthetic characteristics superior to other existing products. Characteristics of the raw materials initially obtained with chemical analysis and mineralogical analysis are crucial in getting a product that satisfies the conditions in a manufacturing process and is, in principle, directly related to the firing cycle. This research aimed at developing new formulations for the mass production of ceramic stoneware. The raw materials initially characterized were feldspar, quartz, kaolin and granite. As part of the research was developed at the University of Aveiro, in Portugal, we used two clays used in the production of Portuguese ceramics. The raw material Brazilian and Portuguese and the final product, both in Portugal and Brazil, were analyzed for X-ray fluorescence, X-ray diffraction, granulometric analysis, dilatometric analysis, thermal analysis and analysis of scanning electron microscopy (MEV). The specimens prepared at the University of Aveiro (DECV) were sintered at 10000C and 12000C and the specimens prepared in UFRN were sintered at 10000C, 10500C, 11000C, 11500C, 12000C, 12500C and 13000C, but the best results and demonstrating the presence of the mineral mullite were at temperatures of 12000C, 12500C and 13000C. The results showed that the granite waste used may be considered raw material of excellent quality for use in the ceramic industry and coating floors and more accurately by the industry of stoneware. Physical and mechanical tests conducted on samples of the formulations F01 and F02 developed in UFRN showed a water absorption and mechanical strength suitable for the stoneware

Desenvolvimento e caracterização de um sistema microemulsionado contendo anfotericina b para uso oftalmológico

Universidade Federal do Rio Grande do Norte

Micropartículas poliméricas à base de xilana e Eudragit® S-100 contendo mesalazina visando à liberação cólon-específica

Colon-specific drug delivery systems have attracted increasing attention from the pharmaceutical industry due to their ability of treating intestinal bowel diseases (IBD), which represent a public health problem in several countries. In spite of being considered a quite effective molecule for the treatment of IBD, mesalazine (5-ASA) is rapidly absorbed in the upper gastrointestinal tract and its systemic absorption leads to risks of adverse effects. The aim of this work was to develop a microparticulate system based on xylan and Eudragit® S- 100 (ES100) for colon-specific delivery of 5-ASA and evaluate the interaction between the polymers present in the systems. Additionaly, the physicochemical and rheological properties of xylan were also evaluated. Initially, xylan was extracted from corn cobs and characterized regarding the yield and rheological properties. Afterwards, 10 formulations were prepared in different xylan and ES100 weight ratios by spray-drying the polymer solutions in 0.6N NaOH and phosphate buffer pH 7.4. In addition, 3 formulations consisting of xylan microcapsules were produced by interfacial cross-linking polymerization and coated by ES100 by means of spray-drying in different polymer weight ratios of xylan and ES100. The microparticles were characterized regarding yield, morphology, homogeneity, visual aspect, crystallinity and thermal behavior. The polymer interaction was investigated by infrared spectroscopy. The extracted xylan was presented as a very fine and yellowish powder, with mean particle size smaller than 40μm. Regarding the rheological properties of xylan, they demonstrated that this polymer has a poor flow, low density and high cohesiveness. The microparticles obtained were shown to be spherical and aggregates could not be observed. They were found to present amorphous structure and have a very high thermal stability. The yield varied according to the polymer ratios. Moreover, it was confirmed that the interaction between xylan and ES100 occurs only by means of physical aggregation

Controle de qualidade físico-químico e biodisponibilidade relativa em ratos de suspensões orais de naproxeno sódico obtidas de farmácias de manipulação na cidade do Natal RN

Compounded medicines have been reported by the ANVISA due to decreased of the therapeutic response or toxicity of these formulations. The aim of this work was to investigate the physicochemical quality control among naproxen sodium oral suspensions 25 mg/mL obtained from six compounding pharmacies (A, B, C, D, E and F) and the manufactured suspension (R). In the quality control test, the tests of pH, content, homogeneity, volume and physical and organoleptic characteristics were performed according to the Brazilian Pharmacopoeia. The analytical method for determination of naproxen in suspensions was validate. This method showed excellent precision, accuracy, linearity and specificity. In the content test the suspensions B, C and E showed lower value and the F suspension showed a high value of the content. The products C and E were disapproved in the description of the physical and organoleptic characteristics test. In the pH test, three suspensions were outside specifications (C, E and F). Only the products R, A and D showed satisfactory results in these tests and therefore they were approved for relative bioavailability test. The R, A and D suspensions were orally administered to Wistar rats and the blood samples were taken at time intervals of 10, 20, 40, 60 min, 3, 4, 6, 24 and 48 h. The plasma samples were immediately stored at 80 ºC until analysis of HPLC. The bioanalytical method validation showed specificity, linearity (R2 0.9987), precision, accuracy, good recovery and stability. The chromatographic conditions were: flow rate of 1.2 mL.min-1 with a mobile phase of acetonitrile : sodium phosphate buffer pH 4.0 (50:50, v/v) at 280 nm, using a C18 column. The confidence interval of 90% for the Cmax and AUCt ratio was within the range of 80 - 125% proposed by the FDA. Only one suspension, obtained from the compounding pharmacy D, was considered bioequivalent to the rate of absorption under the conditions proposed by this study. Thus, the results indicate the need for strict supervision from the relevant authorities to ensure the patient safety and the quality of compounded drugs by pharmacies

Desenvolvimento de emulsões contendo óleos vegetais para uso cosmético

The fat acid esters and tocopherolic derivatives are of great economic interest in many industries. The sunflower oil, which had its rich constitution in these composites, is a very interesting raw material source for the job in some sectors as bio-carburants, bio-lubrificants, bio-surfactants, dispersing agents, food industries, medicines and cosmetics. A system emulsified steady from this oil can wide be used in the therapeutical one, therefore it is of easy acceptance for the patient, for being pharmaceutical forms that allow a better medicine administration. The chemical composition characteristics, rich in unsaturad fat acid and tocopherolic derivatives, the sunflower oil, make of the emulsified systems contend this oil a proposal promising for formularizations of pharmaceutical and cosmetic use with antirust and photoprotection. The general objective of this work was to apply the HLB beddings to determine the sunflower oil critical HLB and, from this, to be able to evaluate the ideal mixture of the constituent of this system through the study of the ternary diagrams for the determination of the ratio of constituent that will generate the emulsion most steady

Estudo de pré-formulação para dose fixa combinada dos tuberculostáticos rifampicina, isoniazida, pirazinamida e etambutol (4 em 1)

According to the global framework regarding new cases of tuberculosis, Brazil appears at the 18th place. Thus, the Ministry of Health has defined this disease as a priority in the governmental policies. As a consequence, studies concerning treatment and prevention have increased. Fixed-dose combination formulations (FDC) are recognized as beneficial and are recommended by WHO, but they present instability and loss on rifampicin bioavailability. The main purpose of this work was to carry out a pre-formulation study with the schedule 1 tuberculosis treatment drugs: rifampicin, isoniazid, pyrazinamide and ethambutol and pharmaceutical excipients (lactose, cellulose, magnesium stearate and talc), in order to develop an FDC product (150 mg of rifampicin + 75 mg of isoniazid + 400 mg of pyrazinamide + 250 mg of ethambutol). The studies consisted of the determination of particle size and distribution (Ferret s diameter) and shape through optical microscopy, as well as rheological and technological properties (bulk and tapped densities, Hausner Factor, Carr s Index, repose angle and flux rate) and interactions among drugs and drug excipient through thermal analysis (DSC, DTA, TG and your derivate). The results showed that, except isoniazid, the other drugs presented poor rheological properties, determined by the physical characteristics of the particles: small size and rod like particles shape for rifampicin; rectangular shape for pyrazinamide and ethambutol, beyond its low density. The 4 drug mixture also not presented flowability, particularly that one containing drug quantity indicated for the formulation of FDC products. In this mixture, isoniazid, that has the best flowability, was added in a lower concentration. The addition of microcrystalline cellulose, magnesium stearate and talc to the drug mixtures improved flowability properties. In DSC analysis probable interactions among drugs were found, supporting the hypothesis of ethambutol and pyrazinamide catalysis of the rifampicin-isoniazid reaction resulting in 3- formylrifamycin isonicotinyl hydrazone (HYD) as a degradation product. In the mixtures containing lactose Supertab® DSC curves evidenced incompatibility among drugs and excipient. In the DSC curves of mixtures containing cellulose MC101®, magnesium stearate and talc, no alterations were observed comparing to the drug profiles. The TG/DTG of the binary and ternary mixtures curves showed different thermogravimetrics profiles relating that observed to the drug isolated, with the thermal decomposition early supporting the evidences of incompatibilities showed in the DSC and DTA curves