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

Segurança do paciente no sistema de medicação: análise de enfermeiros de um hospital de ensino

This study aimed to identify and describe the factors related to Patient Safety in a medication system according to the nurses analysis in a teaching hospital from the photographic analysis method. This was a cross-sectional, descriptive study with mixed approach in a teaching hospital in Rio Grande do Norte. The population consisted of 42 nurses from inpatient units, of which 34 composed the study sample. As eligibility criteria, we defined nurses from public service and nurses who agreed to participate. Ethical determinations were observed, the study was submitted to the Ethics and Research of the University Hospital Onofre Lopes, obtaining the assent with ethical assessment certificate (CAAE 0098.0.051.294-11). For data collection, we used the photographic method (Photographic Analysis Technique) by Patricia Marck (Canada). It was developed in two phases: at first, we randomly captured photos from the medication system, resulting in 282 images; then we selected/processed the photographs, which were reduced to 10 images in Microsoft Excel 2010; in the second phase, the nurses answered the questionnaire divided into socio-professional profile and Digital Photography Scoring Tool (questions a and b ). For analysis of the question a , we used the content analysis technique, and for b , we used the Statistical Package for the Social Sciences 20.0 (temporary license). The socio-professional profile revealed the predominance of females; age group 34-43 years; professionals with specialization; 10-18 years of length of service; and nurses working exclusively in the hospital and who know the Patient Safety. The photographic analysis in relation to Patient Safety resulted in specific categories for each stage of the medication system. Regarding disposal, we identified Proper verification ; Improper verification ; Correct identification ; Disposal in single doses ; and Improper Environment , with predominance of that last category. As for storage: Proper storage ; Improper storage ; Risk of exchange/disappearance ; and Poor hygiene , with special reference to improper storage. In preparation: Risk of exchanging medication/patient ; Inappropriate physical space ; and Inadequate 9 preparation of controlled drugs , highlighting the first category. In drug administration: Lack of Personal Protective Equipment ; Use of Personal Protective Equipment ; Improper administration technique ; Proper administration technique ; Correct drug identification ; Incorrect drug identification ; and Peripheral venous access without identification . From the safety assessment of 10 photographs, by adapting the scores (1-10) to the Likert Scale, we identified three Totally Unsafe (Level 1), three Unsafe (Level 2), three Partially Safe (Level 3), one Safe (Level 4), and no photograph considered Totally Safe. This study identified the prevalence of unsafety in the medication system in the nurses opinion. We were also able to understand that, although nurses identify safety aspects, the most prevalent categories characterize an unsafe assessment. Nursing needs to reflect on its practice, identifying gaps in the medication system in order to achieve a proper and safe care

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.