Abstract In this study, the manufacturing process of lamivudine (3TC) and zidovudine (AZT) tablets (150+300 mg respectively) was evaluated using statistical process control (SPC) tools. These medicines are manufactured by the Fundação para o Remédio Popular “Chopin Tavares de Lima” (FURP) laboratory, and are distributed free of charge to patients infected with HIV by the Ministry of Health DST/AIDS national program. Data of 529 batches manufactured from 2012 to 2015 were collected. The critical quality attributes of weight variation, uniformity of dosage units, and dissolution were evaluated. Process stability was assessed using control charts, and the capability indices Cp, Cpk, Pp, and Ppk (process capability; process capability adjusted for non-centered distribution; potential or global capability of the process; and potential process capability adjusted for non-centered distribution, respectively) were evaluated. 3TC dissolution data from 2013 revealed a non-centered process and lack of consistency compared to the other years, showing Cpk and Ppk lower than 1.0 and the chance of failure of 2,483 in 1,000,000 tablets. Dissolution data from 2015 showed process improvement, revealed by Cpk and Ppk equal to 2.19 and 1.99, respectively. Overall, the control charts and capability indices showed the variability of the process and special causes. Additionally, it was possible to point out the opportunities for process changes, which are fundamental for understanding and supporting a continuous improvement environment.

Abstract The second generation of H1 antihistamines from the piperidine group are often used for treating allergic diseases due to their action on histaminic receptors, the primary mediator of allergy. Moreover, the antihistamines have anti-inflammatory action, mediated through platelet-activating factor blocking activity. A simple and rapid capillary zone electrophoresis method was developed and validated for the determination of loratadine (LOR) and rupatadine (RUP) in tablets. The analyses were carried out using a fused silica capillary of 50.2 cm (40 cm effective length), 75 µm i.d. The background electrolyte was composed of boric acid 35 mmol/L, pH 2.5. Voltage of 20 kV, hydrodynamic injection of 3447.3 Pa for 3s, temperature at 25 ºC, and UV detection at 205 nm were applied. Electrophoretic separation was achieved at 1.8 and 2.8 min for RUP and LOR, respectively. The method was linear for both drugs in a range of 50.0 to 400.0 μg/mL (r>0.99). The limits of detection and quantification were 46.37 and 140.52 μg/mL, for LOR and 29.60 and 89.69 μg/mL for RUP respectively. The precision was less than 5.0 % for both drugs. The average recovery was approximately 100 %. The proposed novel method can significantly contribute to the rapid detection of counterfeit products and in quality control of drug products containing antihistamines.

A derivative spectrophotometric method was validated for quantification of acyclovir in poly (n-butylcyanoacrylate) (PBCA) nanoparticles. Specificity, linearity, precision, accuracy, recovery, detection (LOD) and quantification (LOQ) limits were established for method validation. First-derivative at 295.2 nm eliminated interferences from nanoparticle ingredients and presented linearity for acyclovir concentrations ranging from 1.25 to 40.0 µg/mL (r = 0.9999). Precision and accuracy data demonstrated good reproducibility. Recovery ranged from 99.3 to 101.2. LOD was 0.08 µg/mL and LOQ, 0.25 µg/mL. Thus, the proposed method proved to be easy, low cost, and accurate, and therefore, an useful alternative to quantify acyclovir in nanoparticles.

Entre os tipos de equipamentos de maior relevância utilizados atualmente no processo de revestimento de comprimidos estão os de tambor parcial e totalmente perfurados. A proposta desse trabalho foi avaliar as diferenças de desempenho entre esses equipamentos empregando projeto fatorial. Essa abordagem estatística possibilitou o estudo simultâneo das variáveis do processo, permitindo verificar interações entre elas. O trabalho incluiu equipamento com tambor parcialmente perfurado e totalmente perfurado, solventes aquoso e orgânico, assim como revestimento de liberação imediata à base de hipromelose. As variáveis dependentes ou respostas foram tempo de processo, consumo de energia, peso médio e rendimento do processo. Para os ensaios, foram produzidos comprimidos de placebo de 250 mg de peso médio, divididos em 8 lotes de dois quilogramas cada e revestidos em duplicata, tanto no equipamento com tambor parcialmente perfurado quanto no equipamento de tambor totalmente perfurado, obedecendo a matriz de ensaio previamente definida. Os resultados mostraram que existe diferença significativa entre equipamento de tambor parcialmente perfurado e totalmente perfurado, para tempo de processo e consumo de energia. Já para peso médio dos comprimidos revestidos e rendimento do processo, os dois equipamentos não apresentaram diferença significativa.

Partially and fully perforated pan coaters are among the most relevant types of equipment currently used in the process of coating tablets. The goal of this study was to assess the performance differences among these types of equipment employing a factorial design. This statistical approach allowed the simultaneous study of the process variables and verification of interactions among them. The study included partially-perforated and fully-perforated pan coaters, aqueous and organic solvents, as well as hypromellose-based immediate-release coating. The dependent variables were process time, energy consumption, mean weight of tablets and process yield. For the tests, placebo tablets with a mean weight of 250 mg were produced, divided into eight lots of two kilograms each and coated in duplicate, using both partially perforated pan and fully perforated pan coaters. The results showed a significant difference between the type of equipment used (partially and fully perforated pan coaters) with regard to process time and energy consumption, whereas no significant difference was identified for mean weight of the coated tablets and process yield.

As exigências legais relativas à rotulagem de alimentos, em especial aqueles constituídos de polivitamínicos e minerais destinados a lactentes e crianças de primeira infância, requerem processos de fabricação que assegurem os valores declarados. Dessa forma, os fornecedores de mistura de polivitamínicos devem demonstrar que o processo de homogeneização dos pós conduz aos resultados esperados, conforme especificado. Os estudos de validação devem contemplar tal exigência e podem ser efetuados de forma prospectiva, concorrente ou retrospectiva. A abordagem retrospectiva, fundamentada na revisão e análise de registros históricos, pode ser efetuada no caso dos lotes considerados terem sido produzidos segundo os mesmos parâmetros operacionais e especificações. Assim sendo, o objetivo do presente trabalho foi validar o processo de fabricação de produto constituído pela mistura das seguintes vitaminas: cloridrato de piridoxina, nicotinamida, ácido ascórbico e pantotenato de cálcio, empregando abordagem retrospectiva. A análise estatística dos dados relativos ao teor de cada componente foi efetuada empregando gráficos de controle objetivando a avaliação da estabilidade do processo. Os índices de capacidade Cp e Cpk foram calculados após avaliação da distribuição dos dados empregando teste de Anderson-Darling. Todos os dados apresentaram distribuição normal exceto aqueles relativos ao teor de nicotinamida. Esses dados foram normalizados utilizando método proposto por Box-Cox (lambda igual a -4,24). Os índices de capacidade (Cpk) obtidos foram 1,01, 1,14, 1,21 e 1,96, respectivamente, para cloridrato de piridoxina, nicotinamida, ácido ascórbico e pantotenato de cálcio. Tais resultados indicaram que o processo de mistura de polivitaminas pode ser considerado validado. Além disso, investigações adicionais visando à centralização da concentração teórica, na faixa relativa aos limites de controle, devem ser conduzidas.

The regulatory demands related to the labeling of food, mainly the one constituted of polyvitaminics and minerals destined to lactants and children in their first infancy, require manufactured process that assure the labeled content. Therefore, the suppliers of polyvitaminics have to demonstrate that the process of powder homogeneity leads to expected results, according to the specifications. Thus, the objective of this work was to validate the process of the mixture of the following vitamins: pyridoxine hydrochloride, nicotinamide, ascorbic acid and calcium pantothenate, based on retrospective approach. Control charts were employed for the statistic analysis of the data related to the assay of each vitamin targeting the evaluation of the stability of the process. The capacity indexes, Cp and Cpk, were calculated after the evaluation of the data distribution using Anderson-Darling test. All data showed normal distribution, except for nicotinamide assay. This data was treated by a method proposed by Box-Cox (lambda equal -4.24) aimed at obtaining the normality of the data. The capacity indexes (Cpk) obtained were 1.01, 1.14, 1.21 and 1.96, respectively, for pyridoxine hydrochloride, nicotinamide, ascorbic acid and calcium pantothenate. Therefore, the process of polyvitaminic mixture can be considered validated.

A atividade antimicrobiana de quatro diferentes fórmulas de gel dental foi avaliada empregando três microrganismos associados à cariogênese: Streptococcus mutans, Lactobacillus casei e Actinomyces viscosus. A avaliação preliminar foi efetuada utilizando método por difusão em ágar. Além disso, as fórmulas foram desafiadas empregando cada microrganismo e as determinações relativas aos sobreviventes foram efetuadas após 1, 5, 10, 20 e 30 minutos do desafio. O tempo de redução decimal (valor-D) foi calculado por meio das curvas obtidas (UFC/mL x tempo), objetivando a comparação da atividade antimicrobiana entre as fórmulas. O método selecionado para a enumeração dos sobreviventes foi validado de acordo com compêndio oficial. Os resultados revelaram intensa atividade antimicrobiana, inclusive na avaliação empregando diluição 1:2 dos produtos para os microrganismos Streptococcus mutans e Lactobacillus casei. Os dados relativos ao Actinomyces viscosus indicaram ausência de redução da população microbiana no desafio empregando produto diluído (1:2). Os valores-D obtidos foram 0,21, 2,08, 1,93 e 5,79 minutos para as fórmulas 1, 2, 3 e 4 respectivamente. Após comparação dos resultados obtidos, a fórmula 1 pode ser considerada aquela que apresentou maior atividade antimicrobiana.

The antimicrobial activity of four different dental gel formulas was evaluated on three microorganisms associated with cariogenesis: Streptococcus mutans, Lactobacillus casei and Actinomyces viscosus. The preliminary antimicrobial activity evaluation was performed using an agar diffusion method. In addition, the formulas were challenged using each microorganism with subsequent determinations of survivors at time intervals of 1, 5, 10, 20 and 30 minutes. The decimal reduction time (D-value) calculated from the obtained curves (logCFU/mL vs. time) was employed for the antimicrobial activity comparison of the formulas. The selected method for survivor enumeration was validated according to official compendia. Results revealed intense bactericidal activity, even at 1:2 dilution, on S. mutans and L. casei. The data concerning A. viscosus showed the absence of microbial reduction in the challenge employing diluted formulas at the selected time interval. The obtained D-values were 0.21, 2.08, 1.93 and 5.79 minutes for formulas 1, 2, 3 and 4, respectively. After comparing the obtained results, formula 1 can be considered to have the highest bactericidal activity.

A validação de método para a avaliação da qualidade sanitária de produto cosmético de base lipófila foi efetuada empregando-se neutralizantes químicos e diluição para a eliminação de efeito inibitório no crescimento microbiano. Para a preparação da amostra foi empregado miristato de isopropila e polissorbato 20. Além dessas substâncias, foi adicionado ao diluente 0,5% (p/v) de lecitina de soja visando à neutralização do cloreto de benzalcônio. Os ensaios foram efetuados objetivando a comprovação da ausência de efeito inibitório no crescimento microbiano decorrente de atividade antimicrobiana do produto, assim como dos agentes neutralizantes, tensoativos e solubilizante empregados no ensaio. Na avaliação quantitativa, os resultados demonstraram ausência de efeito inibitório no crescimento microbiano nas diluições 1:10 e 1:100. A porcentagem de microrganismos recuperados foi de, no mínimo, 93,2% indicando a validade do método de acordo com o critério oficial adotado. Com referência ao ensaio qualitativo, foi observado efeito inibitório na diluição 1:20 para os seguintes microrganismos: Pseudomonas aeruginosaeStaphylococcus aureus.Esse efeito foi eliminado empregando-se diluição 1:200, sendo, desta forma, essa diluição considerada válida para o ensaio.

The validation of method to evaluate the sanitary quality of lipophilic base cosmetics was performed using chemical neutralizers and dilution in order to eliminate the inhibitory effect on the microbial growth. The preparation of the sample was performed aiming the homogeneity in the culture media. Isopropyl miristate was used for the solubilization of the sample and polysorbate 20 was used as surfactant. Besides these substances, it was added to the diluent 0.5% (w/v) of soy lecithin to neutralize the antimicrobial activity of the benzalkonium chloride. The purpose of the assays was to demonstrate the lack of inhibitory effect on the microbial growth due to antimicrobial activity of the product as well as of the neutralizing and solubilizing agents and the surfactant used in the assay. With regard to a quantitative evaluation, the results showed a lack of inhibitory effect of the product on the microbial growth in dilutions 1:10 and 1:100. The percentage of microbial recovery was at least 93.2% indicating the validation of the method in accordance with the official criteria adopted. As for the qualitative analysis, in dilution 1:20, it was noticed an inhibitory effect for the following microorganisms: Pseudomonas aeruginosa and Staphylococcus aureus.Since this mentioned effect was not noticed when dilution was 1:200, the latter dilution was considered valid for the assay.