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

Interpretação sísmica e análise de atributos - área do levantamento sísmico 3D de siririzinho (Bacia Sergipe-Alagoas, NE do Brasil)

The main objective of the present thesis was the seismic interpretation and seismic attribute analysis of the 3D seismic data from the Siririzinho high, located in the Sergipe Sub-basin (southern portion of Sergipe-Alagoas Basin). This study has enabled a better understanding of the stratigraphy and structure that the Siririzinho high experienced during its development. In a first analysis, we used two types of filters: the dip-steered median filter, was used to remove random noise and increase the lateral continuity of reflections, and fault-enhancement filter was applied to enhance the reflection discontinuities. After this filtering step similarity and curvature attributes were applied in order to identify and enhance the distribution of faults and fractures. The use of attributes and filtering greatly contributed to the identification and enhancement of continuity of faults. Besides the application of typical attributes (similarity and curvature) neural network and fingerprint techniques were also used, which generate meta-attributes, also aiming to highlight the faults; however, the results were not satisfactory. In a subsequent step, well log and seismic data analysis were performed, which allowed the understanding of the distribution and arrangement of sequences that occur in the Siririzinho high, as well as an understanding of how these units are affected by main structures in the region. The Siririzinho high comprises an elongated structure elongated in the NS direction, capped by four seismo-sequences (informally named, from bottom to top, the sequences I to IV, plus the top of the basement). It was possible to recognize the main NS-oriented faults, which especially affect the sequences I and II, and faults oriented NE-SW, that reach the younger sequences, III and IV. Finally, with the interpretation of seismic horizons corresponding to each of these sequences, it was possible to define a better understanding of geometry, deposition and structural relations in the area.