Detecção de desvios de qualidade nos medicamentos manipulados: solução de ácido acético, xarope de cetoconazol e cápsulas de hormônio tireoidiano T4 / Detection of quality deviations in compounded formulation: acetic acid solution, ketoconazole syrup and T4 thyroid hormone capsules

Introdução: Doses incorretas do ativo nas preparações magistrais configuram erros comuns na manipulação, podendo ocasionar agravos à saúde do paciente, refletindo possível ausência das Boas Práticas de Manipulação (BPM). Objetivo: Relatar desvios de qualidade nos medicamentos solução de ácido acético, xarope de cetoconazol e cápsulas de T4. Método: Identificação por reações químicas e por CLAE, teor por titulação e CLAE, pH por potenciometria. Resultados: Identificação positiva, para ácido acético com teor de 98,20% compatível com ácido acético glacial, em desacordo com a prescrição de solução a 5%. O teor de cetoconazol de 16,20 mg/mL encontrado no xarope corresponde a 81,00% do declarado, com especificação mínima de 90,00%; pH 8,0; identificação positiva para tensoativo aniônico componente saponáceo, no xarope. Os resultados encontrados: cápsulas de T4 de 25 µg foi de 177,70 µg e as de 200 µg foi de 174,44 µg, correspondendo a 710,96% e 87,22% do teor declarado, respectivamente, em desacordo com a especificação de 90,00% a 110,00%. Conclusões: O trabalho ilustrou a detecção de desvios de qualidade em medicamentos manipulados de diferentes farmácias, decorrentes de erros farmacotécnicos, ausência de controle de qualidade e falta de implementação das BPM. A frequente fiscalização previne riscos sanitários à população.

Introduction: Incorrect doses of the active ingredient in compounding formulations make up common errors in the manipulation, which can cause harm to the patient's health,reflecting the possible absence of Good Handling Practices (GHP). Objective: To report quality deviations in the medicines acetic acid solution, ketoconazole syrup and T4 capsules. Method: Identification by chemical reactions and by HPLC, content by titration and HPLC, pH by potentiometry. Results: Positive identification for acetic acid with 98.20% content compatible with glacial acetic acid, in disagreement with the prescription of 5% solution. The ketoconazole content of 16.20 mg/mL found in the syrup corresponds to 81.00% of the declared, the minimum specification is 90.00%; pH 8.0; positive identification for anionic surfactant component in the syrup. The results found were: 25 µg T4 capsules were 177.70 µg and for the 200 µg capsules it was 174.44 µg, corresponding to 710.96% and 87.22% of the declared content, respectively, in disagreement with specification 90.00% and 110.00%. Conclusions: The study illustrated the detection of quality deviations in manipulated drugs from different pharmacies, due to pharmacotechnical misconceptions, lack of quality control and lack of GHP implementation. Frequent inspection prevents health risks to the population.

Physicochemical quality evaluation of amoxicillin capsules produced in compounding pharmacies at Diadema, São Paulo, Brazil.

The evaluation of the physicochemical quality of amoxicillin (500 mg) capsules produced in Compounding Pharmacies at Diadema - SP - Brazil, was performed by comparing these capsules with reference, generic and similar drugs, through the dissolution, assay, average weight, water content analysis, all according to the pharmacopeial methodology. The compounded drug samples were acquired on 8 different Compounding Pharmacies of Diadema (M1, M2, M3, M4, M5, M6, M7, M8), and five (reference, generic and similar) drug samples (R, G1, G2, S1, S2) produced by distinct pharmaceutical industries were obtained from different Drugstores also at the same area. The samples were evaluated using the methodology proposed by the American and Brazilian Pharmacopoeia. All samples were approved in the dissolution and water content assay. Only samples R and S1 were approved assay of dose. Samples M3, M4 and S1 were disapproved in the average weight assay. The non-fulfillment of the Brazilian Good Manufacturing Practices recommended procedures for industries and compounding pharmacies show the need for improvements in the overall drug quality control manufacturing process of finished products in consonance with the actual health legislation, guaranteeing access to safe, effective medicines, control of bacterial resistance and rational use of antibiotics.

Evaluation and study of mebendazole polymorphs present in raw materials and tablets available in the Brazilian pharmaceutical market.

The dissolution of a drug can be compromised by the presence of different polymorphs, which may have different solubilities. Importantly, the pharmacopoeiamonographs,usually not have tests for the characterization of these polymorphic forms of a drug. Was performed a study of polymorphic forms of mebendazole present in raw materials and also pills available in the Brazilian pharmaceutical market through the techniques of infrared (FTIR), differential scanning calorimetry (DSC), dissolution , solubility and X-ray diffraction pattern (XRPD). Through the analysis of FTIR and DSC curves showed that there are three main polymorphic forms of mebendazole present in raw materials and tablets that compound. The data obtained in the dissolution and solubility tests showed that Form A is less soluble than Form B which is less soluble than the C form, when using a dissolution medium without added surfactant. It has been found that in some tablets mebendazole there is a mixture of polymorphic forms, and that the raw materials present two major polymorphic forms. Then it is suggested the need of quality control regarding the type of polymorph used in the production of mebendazole tablets to ensure greater therapeutic efficacy.

Evaluation of the quality and stability of amoxicillin oral suspension.

The laboratory control of diseases frequently receives powders for oral suspension of amoxicillin, with reports of therapeutic ineffectiveness and problems in reconstituting suspensions. The compendial analyzes not shows quality deviations. This fact motivated the study to assess the quality and stability of oral suspensions amoxicillin in the period of use corresponding to the first and seventh days after reconstitution. Six generic drugs were tested along with the referential drug during its intake period, from the first to the seventh day after powder reconstitution for suspension by high performance liquid chromatographic method. The reconstitution of all samples resulted in suspensions with homogeneous aspect. Both pH assay and amoxicillin identification complied with the product’s specification. The amoxicillin rates were determined in the 1th and 7th days after the reconstitution of samples through a method for stability detection, developed and validated before. At the 1th day, a generic drug sample presented 78% of the rate declared, below the lowest-value specification (90%). In the 7th day, 3 generic drug samples presented rates below 87%, 83% and 68.1% of the declared value, lower than the minimal specification, thus evidencing pharmacotechnical flaws in the product because of its lack of stability. Percent degradation rates of 3.5%, 4.0%, 6.0%, 9.9%, and 15% amoxicillin in 5 of the generic formulations studied are significant. The present study about amoxicillin oral suspension provides information about the stability during the using period, described for manufacturers. Even though the degradation products have not been identified, they can compromise their safe use, meaning potential risks to the users because of possible toxicity and/or therapeutic inefficacy.

Development and Validation of RP-HPLC Method for the Determination of Related Compounds in Quetiapine Hemifumarate Raw Material and Tablets.

A simple and sensitive high performance liquid chromatographic method has been developed for the determination of assay quantitative of related compounds and quetiapine hemifumarate in raw material and tablets. Quetiapine hemifumarate is used for the treatment of schizophrenia and there are some generic medicines available in brazilian marketing pharmaceutical, it´s necessary evaluate the quality control of raw material used in the production. Efficient chromatographic separation was carry out on a C18 stationary phase with mobile phase consisting in a mixture of phosphate buffer pH 6.6:Acetonitrile:Methanol (45:40:15), flow rate of 1.0 mL min-1, injection volume of 20 μL, temperature of 25 °C and ultraviolet detection at 220 nm. All of the chromatographic parameters were attended, with resolution greater than 2.9 between quetiapine hemifumarate and impurities. The HPLC method was validated according ICH guidelines, evaluating selectivity, limits of detection and quantification, linearity, accuracy, precision and robustness. The relative retentions times were about 0.58, 0.69 and 0.88 to related compounds, piperazine, lactam and ethanol compound, respectively. Impurities were found < 0.1 % in samples and the assay of quetiapine hemifumarate was > 98.15%. The method can be used for the routine analysis of the impurities in Quetiapine hemihumarate (QH) without any interference.

Avaliação da qualidade de cápsulas de sinvastatina de farmácias magistrais / Evaluación de la calidad de cápsulas de sinvastatina de farmacias magistrales / Assessment of the quality of simvastatin capsules from compounding pharmacies

OBJETIVO: Validar metodologia por cromatografia líquida de alta eficiência para determinação do teor de sinvastatina em cápsulas manipuladas. MÉTODOS: Foram avaliadas 18 amostras de cápsulas de sinvastatina 40 mg de farmácias magistrais de São Paulo, Guarulhos, São Bernardo do Campo e Campinas, SP, prescritas para pacientes fictícios. As análises basearam-se na Farmacopéia Brasileira e no método da cromatografia, otimizado e validado de acordo com as normas nacionais e internacionais, para os ensaios de identificação, e quantificação em cápsulas manipuladas. RESULTADOS: O peso médio das cápsulas variou de 70 mg a 316 mg; quatro amostras apresentaram variação de peso em desacordo com a especificação. O teor de sinvastatina nas cápsulas estava de acordo com a especificação em 11 amostras; em seis, esse teor variou entre 4 por cento e 87 por cento do valor declarado, descumprindo os requisitos de teor do princípio ativo; a determinação do teor e uniformidade de conteúdo de uma amostra não foram realizadas. No teste de uniformidade de conteúdo, 15 amostras apresentaram valores menores que 85 por cento e com os desvios-padrões relativos maiores que 6 por cento; três farmácias atendiam a especificação desse ensaio. No ensaio de dissolução, oito amostras apresentaram resultados insatisfatórios no primeiro estágio do ensaio e as demais apresentaram resultados inconclusivos. CONCLUSÕES: O método utilizado mostrou boa adequação para aplicação em controle de qualidade, revelando a falta de qualidade de cápsulas de sinvastatina produzidas por algumas farmácias de manipulação.

OBJETIVO: Validar metodología por cromatografía líquida de alta eficiencia para determinación del tenor de sinvastatina en cápsulas manipuladas. MÉTODOS: Fueron evaluadas 18 muestras de cápsulas de sinvastatina 40 mg de farmacias magistrales de Sao Paulo, Guarulhos, Sao Bernardo do Campo y Campinas, Sureste de Brasil, prescriptas para pacientes ficticios. Los análisis se basaron en la Farmacopéia Brasileña y en el método de la cromatografia, optimizado y validado de acuerdo con las normas nacionales e internacionales, para los ensayos de identificación, y cuantificación en cápsulas manipuladas. RESULTADOS: El peso promedio de las cápsulas variaron de 70 a 316 mg; cuatro muestras presentaron variación de peso en desacuerdo con la especificación. El tenor de sinvastatina en las cápsulas estaba de acuerdo con la especificación en 11 muestras; en seis, ese tenor varió entre 4% y 87% del valor declarado incumpliendo los requisitos de tenor del principio activo; la determinación del tenor y uniformidad de contenido de una muestra no fue realizada. En la prueba de uniformidad de contenido, 15 muestras presentaron valores menores que 85% y con los desvíos-patrones relativos mayores que 6%; tres farmacias atendían la especificación del ensayo. En el ensayo de disolución, ocho muestras presentaron resultados insatisfactorios en la primera fase del ensayo, y las demás presentaron resultados inconclusitos. CONCLUSIONES: El método utilizado mostró buena adecuación para aplicación en control de calidad, revelando la falta de calidad de cápsulas de sinvastatina producidas por algunas farmacias de manipulación.

Avaliaçäo da qualidade de comprimidos revestidos e soluçöes orais de sulfato ferroso utilizados no tratamento da anemia ferropriva / Quality control of ferrous sulphate tablets and oral solutions used on the iron-deficiency anaemia

Foram analisados 41 medicamentos à base de sulfato ferroso apresentados na forma de soluçäo e comprimidos revestidos e encaminhados pelo SUS-SP, como análises fiscais, para controle da qualidade. Das 41 amostras analisadas, 15(37 por cento) näo atenderam às especificaçöes de qualidade quanto ao teor de sulfato e de ácido ascórbico (presente em algumas amostras em associaçäo com o sulfato ferroso), quanto aos aspectos farmacotécnicos e quanto ao rótulo. Em funçäo da importância do uso terapêutico destes medicamentos no combate às anemias ferroprivas, principalmente em crianças, adolescentes e mulheres em idade fértil, é fundamental que se estabeleçam programas de monitoramento de controle de qualidade para garantir a eficácia dos mesmos

Elementos histológicos característicos de Cecropia pachystachya Trécul (embaúba) / Histological elements characteristic of pachystachya Trécul Cecropia (Cecropia)

São descritas as características anatômicas da folha, do pecíolo e das cascas caulinares da espécie Cecropia pachystachya Trécul com o objetivo de identificar o vegetal fragmentado, empregado medicinalmente. Anexos epidérmicos e inclusões celulares permitem a diagnose a partir das folhas. Peculiaridades das fibras, dos esclereídeos e dos vasos permitem o reconhecimento através das cascas.

Anatomical characteristics of the leaf and the barks of the stem of the species Cecropia pachystachya Trécul are described aiming to identify this species when it is employed for therapeutic purposes. Epidermal annexs and cellular inclusions allow the diagnosis of the species from its leaves. Peculiarities of the fibers, petrea cells and vases allow the recognizing of the barks of the stem of Cecropia pachystachya Trécul.

Caracterizaçäo histológica das folhas e dos frutos de Rubus rosaefolius smith(amora-do-mato) / Histologycal characterization of the leaves and fruits of Rubus rosaefolius smith

Folhas e frutos de Rubus rosaefolius smith foram estudadas anatomicamente com o objetivo de fornecer subsídios para a identificaçäo da espécie. As folhas säo compostas e os folíolos tem margens duplamente denteadas. Apresentam como anexos epidérmicos: um tricoma tector unicelular de aproximadamente 400 mm de comprimento, e dois tipos de tricomas glandulares, um de cabeça esférica e outro de cabeça lenticular, sendo ambos pluricelulares. Drusas ocorrem mais abundantemente nas folhas do que nos frutos. As sépalas tem farta cobertura pilosa sobre a epiderme superior. Os frutos näo contém amido