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Abstract This study aimed to develop and evaluate the stability of sulfadiazine sugar-free extemporaneous oral suspensions, focusing on treating congenital toxoplasmosis. The excipients were carefully chosen to obtain safe products for the pediatric population. Sulfadiazine suspensions (100 mg/ mL) were prepared from the raw material or tablets, stored in amber glass bottles at 5±3ºC, and evaluated at 0, 14, and 30 days. An ultra-performance liquid chromatographic method was developed and validated to assay the drug. The particle size ranged from 29.3 to 50.6 µm, with some variation over the study; pH values around 7.0 and non-Newtonian behavior were observed without modification in the period. Formulations showed a fast dissolution rate (>80% in 15 minutes) without variation over the study. The drug assay was about 100% of the label claimed throughout the study, demonstrating the chemical stability and the preparations' dose homogeneity. The microbiological investigation indicated that both preparations met the requirements for the microbial count and absence of pathogens. In conclusion, the developed formulations can be used for 30 days when stored under refrigeration. The oral suspensions produced are easy to prepare and contain safe components, providing an alternative for congenital toxoplasmosis treatment in children

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BACKGROUND: Extemporaneous compounding (EC) involves the preparation of a therapeutic product for specific patient need. However, there is a potential relationship between this procedure and the occurrence of health incidents (HI). The use of trigger tools increases HI identification. OBJECTIVE: This study assessed the performance of EC as a trigger to detect potential health incidents arising from this procedure. METHODS: A one-month observational and cross-sectional study was performed in internal medicine ward and intensive care unit of medium-sized hospital. Data collection was carried out in 5 stages: all triggered patients with dysphagia or enteral feeding tube with prescription of EC were included; EC executed in prescribed standardized drugs was observed; the procedure was compared with the hospital guide and scientific literature; HI monitoring and their evaluation using WHO and NCC MERP algorithms; a search for pharmaceutical alternatives (PA) that would avoid the observed EC. RESULTS: 197 patients were recruited. Almost half of them were triggered by EC from 84 standardized drugs. 48 patients met the inclusion criteria. 28 adverse drug reactions, 01 therapeutic ineffectiveness, and 29 medication errors were identified. EC as a trigger tool showed a PPV value of 0.38. Only 24 drugs have PA available in the market, which could avoid one third of all observed EC. CONCLUSION: It was possible to detect potentially HI in one of two patients with enteral feeding tubes using EC as a trigger tool. The use of EC as a trigger tool contributes to identifying potential HI arising from drugs, which have not gotten pharmaceutical alternatives to be administered via enteral feeding tube.

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Metformin pharmacokinetics in a liquid extemporaneous formulation from commercial tablets was determined in paediatric patients. A randomized, transversal clinical trial was conducted in 34 children and adolescents between 7 and 17 years of age. 17 children were randomized to take metformin in the liquid formulation and, after a 1-week wash period, a 500 mg metformin tablet was administered to them. Blood samples were obtained in Whatman 903® cards at 0, 1, 2, 4, 8, 12 and 24 hours. Extraction was made by direct precipitation with acetonitrile (ACN) and methanol, detection by UPLC and tandem mass spectrometry. The method was accurate, precise, selective and linear from 50 to 1000 ng/mL (r = .9982). Comparative pharmacokinetics, tablet vs formulation, were as follows: Cmax 1503.2 ng/mL vs 1521.4, Tmax 1.5 h vs 2.3, and half-life 8.2 vs 7.5 h. The liquid formulation of metformin showed similar pharmacokinetics to the tablet, and the ratios (90% CI) of geometric mean for metformin were 100.63% (89.13-113.6), 98.08% (88.04-109.2), and 97.52% (84.9-112.01), for Cmax, AUC0-t, and AUC 0-∞, respectively. Pharmacokinetics was determined using WinNonlin Pro 3.1 software. The liquid formulation of metformin showed similar pharmacokinetics to the tablet, allowing a more precise dose adjustment and ease of administration.

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Onychomycosis induced by Candida spp. has several limitations regarding its treatment. Nail lacquers display the potential to overcome these drawbacks by providing therapeutic compliance and increasing local drug bioavailability. Thus, this work aimed to produce a nail lacquer loaded with Amphotericin B (AmB) and evaluate its performance. The AmB-loaded nail lacquer was produced and preliminarily characterized. An AmB quantification method was developed. Stability, drug release, permeability and anti-Candida activity assays were conducted. The analytical method validation met the acceptance criteria. The drug loading efficiency was 100% (0.02 mg/g of total product), whereas the AmB stability was limited to ≅7 days (≅90% remaining). The nail lacquer displayed a drying time of 187 s, non-volatile content of around 20%w/w, water-resistance of approximately 2%w/w of weight loss and satisfactory in vitro adhesion. Moreover, the in vitro antifungal activity against different Candida spp. strains was confirmed. The AmB release and the ex vivo permeability studies revealed that AmB leaves the lacquer and permeates the nail matrix in 47.76 ± 0.07% over 24 h. In conclusion, AmB-loaded nail lacquer shows itself as a promising extemporaneous dosage form with remarkable anti-Candida activity related to onychomycosis.

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Resumo: O presente ensaio trata de pensar uma subjetividade literária e, com ela, uma via clínica propícia ao entendimento do conceito de sublime-ação, assim grafado devido à renovação de seu uso. Considera a obra e, em certo sentido, a vida do escritor Wilson Bueno, extraindo de seu entrelaçamento consequências analíticas que trazem, a um mesmo plano de exame, as noções de sublime-ação e sinthoma, esta última tal como é concebida por Lacan. Serão ainda empregados conceitos deleuzianos, nietzschianos e bergsonianos que devem oferecer perspectivas éticas e clínicas de inesperado alcance ao saber analítico.

Abstract: This essay deals with thinking about a literary subjectivity and, with it, a clinical way conducive to understanding the concept of sublime-action, thus spelled due to the renewal of its use. It considers the work and, in a sense, the life of the writer Wilson Bueno, drawing from its intertwining analytical consequences that bring to the same plane of examination the notions of sublime-action and synthoma, the latter as conceived by Lacan. Deleuzian, Nietzschean, and Bergsonian concepts that should offer ethical and clinical perspectives of unexpected scope to analytical knowledge will also be employed.

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OBJECTIVES: To determine the physicochemical and microbiological stability of sulfadiazine suspensions (100 mg/mL) in simple syrup (A) and sorbitol (B) formulations prepared from commercially available tablets. METHODS: An ultra-performance liquid chromatographic assay was developed and validated to determine the chemical stability of sulfadiazine. Three samples were prepared and stored at 5 and 25 °C and assayed at 0, 7, 14 and 30 days. Physical parameters (appearance, pH, particle size and viscosity) were also monitored. Microbiological examination was performed through the suitable counting method. RESULTS: The formulations presented a sulfadiazine concentration of around 95% at the beginning at both temperatures. There was some variation in pH, viscosity and particle size distribution over time. The samples met the pharmacopoeia criteria of microbiological quality over 30 days, but only sulfadiazine formulated in syrup stored at 25 °C was suitable for use after one week. CONCLUSION: The sulfadiazine suspension in simple syrup was chosen as the most suitable formulation because it demonstrated stability for 14 days at room temperature, providing an alternative liquid dosage form of sulfadiazine for congenital toxoplasmosis treatment.

OBJECTIFS: Déterminer la stabilité physicochimique et microbiologique de suspensions de sulfadiazine (100 mg/mL) dans des formulations de sirop simple (A) et de sorbitol (B) préparées à partir de comprimés disponibles dans le commerce. MÉTHODES: Un test de chromatographie liquide ultra-performante a été développé et validé pour déterminer la stabilité chimique de la sulfadiazine. Trois échantillons ont été préparés et stockés à 5 ºC et à 25 ºC et analysés à 0, 7, 14 et 30 jours. Les paramètres physiques (apparence, pH, granulométrie et viscosité) ont également été contrôlés. Un examen microbiologique a été effectué par la méthode de comptage appropriée. RÉSULTATS: Les formulations présentaient une concentration en sulfadiazine d'environ 95% au début aux deux températures. Il y avait une certaine variation du pH, de la viscosité et de la distribution de la taille des particules au fil du temps. Les échantillons répondaient aux critères de pharmacopée pour la qualité microbiologique aprè 30 jours, mais seule la sulfadiazine formulée dans du sirop conservé à 25 ºC pouvait être utilisée après une semaine. CONCLUSION: La suspension de sulfadiazine dans un sirop simple a été choisie comme la formulation la plus appropriée car elle a démontré une stabilité à 14 jours à température ambiante, fournissant une forme galénique liquide alternative de sulfadiazine pour le traitement de la toxoplasmose congénitale.

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At the hospital, the pharmacist is constantly challenged to prepare extemporaneous solutions from tablets, capsules or drug powder for patients unable to swallow, such as pediatric, elderly and patients that use nasoenteric and nasogastric tubes. The preparation of extemporaneous solutions from capsules, tablets and drug powder requires stability studies analysis. This article is a bibliographic review of preparation of extemporaneous oral liquid from solid oral dosage forms used in clinical practice. The selected articles contain all the information regarding manipulation techniques, pharmaceutical excipients, packaging, storage conditions and results of stability studies above 90% performed by HPLC analysis. In addition, a situational analysis of the strategies for the preparation of the extemporaneous solution was described to help the manipulator in the decision. The preparation of extemporaneous solution from solid oral dosage forms is based on information from official compendium or scientific literature, to ensure safe and effective manipulated medicine.

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The purpose of this study was to develop extemporaneous liquid pharmaceutical formulations from commercial tablets containing spironolactone and to assess their stability for use in children or adults with difficulty in swallowing. The content and stability of spironolactone in the tablets, as well as in water, 1.5% carboxymethylcellulose (CMC) or simple syrup dispersions were determined by high performance liquid chromatography (HPLC) analysis on a C18 silica column (250 mm ? 4.6 mm ? 5 ?m), with a mobile phase of methanol:water (75:25 v/v), flowing at 1 mL/min, and UV detection at 240 nm. The extemporaneous formulations were tested over a 35-day period at 8, 27, and 40 ºC. Drug content in the aqueous dispersion was far lower than expected, with significant fluctuations at all temperatures, owing to rapid sedimentation. The content proved adequate in aqueous 1.5% CMC dispersion at 27 ºC, with undesirable variations at the other temperatures. The syrup-based dispersion remained stable at all three temperatures, with suitable drug content and no significant variability. No degradation products were observed in any of the formulations. The syrup-based dispersion is easy to prepare, self-preserving, stable, palatable, offering satisfactory drug content per dose, and can therefore be recommended as an extemporaneous formulation for enhancing treatment adherence and effectiveness...

O objetivo desse trabalho foi desenvolver e avaliar a estabilidade de formas farmacêuticas líquidas extemporâneas, a partir de amostras comerciais (comprimidos), contendo espironolactona, para que possam ser empregadas em pacientes pediátricos ou adultos com dificuldade de deglutição. A metodologia empregada para a análise do teor e da estabilidade do fármaco espironolactona nos comprimidos e nas dispersões utilizando água, carboximetilcelulose (CMC) 1,5% e xarope simples foi a Cromatografia Líquida de Alta Eficiência (CLAE), utilizando coluna de sílica C18 (250 mm x 4,6 mm x 5 μm), fluxo de 1 mL/min, comprimento de onda 240 nm e fase móvel metanol:água (75:25 v/v). As formulações extemporâneas foram analisadas durante 35 dias nas temperaturas de 8, 27 e 40 ºC. A dispersão aquosa apresentou teor muito abaixo do esperado, com variações significativas em todas as temperaturas, devido à rápida sedimentação. A dispersão aquosa de CMC 1,5% apresentou teor adequado na temperatura de 27 ºC com variações indesejadas nas demais temperaturas. A dispersão de xarope simples apresentou-se estável nas três temperaturas, com teor adequado e sem variações significativas. Não foi observado produto de degradação em nenhuma das formulações propostas. Por ser de fácil preparação, autoconservante, estável e de sabor agradável, a dispersão de xarope simples é a formulação extemporânea recomendada, pois garante teor satisfatório por dose e, portanto, favorece aumento à adesão e à eficácia do tratamento...

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BACKGROUND: Coadministration of rifampicin (RIF)/isoniazid (INH) is clinically recommended to improve the treatment of tuberculosis. Under gastric conditions, RIF undergoes fast hydrolysis (a pathway hastened by INH) and oral bioavailability loss. AIM: We aimed to assess the chemical stabilization and the oral pharmacokinetics of RIF nanoencapsulated within poly(ε-caprolactone)-b-PEG-b-poly(ε-caprolactone) 'flower-like' polymeric micelles. MATERIALS & METHODS: The chemical stability of RIF was evaluated in vitro under acid conditions with and without INH, and the oral pharmacokinetics of RIF-loaded micelles in rats was compared with those of a suspension coded by the US Pharmacopeia. RESULTS: Nanoencapsulation decreased the degradation rate of RIF with respect to the free drug. Moreover, in vivo data showed a statistically significant increase of RIF oral bioavailability (up to 3.3-times) with respect to the free drug in the presence of INH. CONCLUSION: Overall results highlight the potential of this nanotechnology platform to develop an extemporaneous liquid RIF/INH fixed-dose combination suitable for pediatric administration.

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En este trabajo se llevó a cabo el desarrollo y la validación de una metodología analítica por HPLC para la cuantificación de Warfarina Sódica en una suspensión para uso hospitalario. La selectividad se evaluó frente a los excipientes y compuestos de degradación; la linealidad en el rango de concentraciones comprendido entre 0,05 y 0,15 mg/mL; la precisión se estudió en los niveles de repetibilidad y precisión intermedia y la exactitud en tres niveles de concentración que corresponden al 75%, 100% y 125%. Los resultados muestran que la validación de la metodología por HPLC es selectiva, lineal, precisa y exacta; por tanto, es confiable para ser utilizada en la cuantificación del activo Warfarina Sódica en una suspensión extemporánea y también en estudios de estabilidad de dicha preparación.

In this work was carried out the development and quantification of an analytical methodology for quantification of Warfarin Sodium in an extemporaneous suspension for hospital use. Evaluation of specificity was achieved against its excipients and degradation compounds. The selectivity was evaluated against the excipients and degradation compounds. Linearity studies were performed in a range of concentration between 0.05 to 0.15 mg/mL. Precision was evaluated in levels of repeatability and intermediate precision and accuracy in three concentration levels corresponding to the 75, 100 and 125%. The results show that the validation of the methodology is selective, linear, accurate and precise; therefore, it is reliable for use in the quantification of active warfarin sodium in the extemporaneous suspension.

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O uso frequente de medicamentos off-label ou não licenciados na área da pediatria é um problema mundial que ocorre devido à indisponibilidade de formas farmacêuticas adequadas com dosagens apropriadas para a administração em crianças. Durante a internação, tal dificuldade pode ser contornada a partir da derivação de formas farmacêuticas sólidas, originando as chamadas preparações líquidas extemporâneas. Porém, para garantir o uso dos medicamentos após a alta hospitalar mesmo quando a família não pode pagar a manipulação destes, faz-se necessária uma orientação adequada de como realizar a derivação em casa pelo próprio cuidador do paciente. Objetivos: elaborar e avaliar um material educativo impresso (MEI) para auxiliar na preparação de medicamentos extemporâneos pós-alta hospitalar em pediatria. Métodos: Foi elaborada uma primeira versão de MEI e avaliada por 26 profissionais da saúde por meio do instrumento EVALPEM (Evaluation of Printed Education Materials) modificado. A partir das contribuições dos profissionais foi elaborada uma segunda versão avaliada por 5 cuidadores de crianças utilizando-se o questionário adaptado de Doak. Resultados: a primeira versão do MEI foi bem aceita pela maioria dos profissionais, onde 80,8% dos participantes consideraram as informações como sendo de qualidade e 87,5% concordaram totalmente com o domínio, legibilidade e características de impressão. A segunda versão obteve 89,1% no domínio compreensão, 90,6% em autoeficácia e 100% em atratividade, aceitação cultural e persuasão. Conclusões: o MEI demonstrou ser uma ferramenta importante para orientar o preparo

The frequent use of non-licensed or off-label drugs in pediatrics is a world problem that occurs due to the unavailability of appropriate pharmaceutical forms with proper doses to administration in children. During hospitalization, this difficulty can be avoided with the derivation of solid pharmaceutical forms, originating the so-called extemporaneous liquid preparations. Nevertheless, to guarantee the use of medication after hospital discharge – especially when the family cannot pay for its manipulation –, it is necessary to provide appropriate guidance to caregivers on how to prepare the derivation at home. Aim: to create and evaluate printed educational material (PEM) to help in the preparation of extemporaneous formulations after hospital discharge in pediatrics. Methods: a first version of the PEM was created and evaluated by 26 health workers, using the instrument EVALPEM (Evaluation of Printed Education Materials) modified. From the contribution of these professionals, a new version was developed and evaluated by five children caregivers, using an adaptation of the Doak questionnaire. Results: The first version of the PEM was well-accepted by most of the professionals, as 80.8% of them completely agreed about the quality of the information and 87.5% totally agreed about the legibility and printing features. The second version received 89.1% of approval in the field understanding, 90.6% in self-effectiveness, and 100% in atractiveness, cultural acceptance, and persuasion. Conclusions: The PEM proved to be an important tool to guide the correct preparation and administration of extemporaneous formulations by the caregivers of pediatric patients

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En este artículo se presentan los resultados del desarrollo, estandarización y validación de una metodología analítica por cromatografía líquida de alta eficiencia para la cuantificación de fenobarbital en una suspensión extemporánea, usando butobarbital como est¨¢ndar interno. El método cromatográfico utiliza un detector uv con arreglo de diodos (dad) como sistema de detección, una fase móvil compuesta por una mezcla de metanol y agua (48:52) adicionada de H3PO4 al 0,1% y una columna cromatográfica C18 estabilizada a una temperatura de 35 ºC. La metodología validada fue selectiva, lineal, precisa y exacta. La linealidad se evalua para concentraciones entre 4,8 y 24 μg/mL. La metodología desarrollada se utilizó para llevar a cabo el estudio de estabilidad de una suspensión extemporánea de fenobarbital, utilizada en la Clínica Country para el tratamiento de las convulsiones en pacientes pediátricos.

In this article we present the data obtained during the development, standardization and validation of a high performance liquid chromatography method for the quantification of phenobarbital in an extemporaneous suspension using butobarbital as internal standard. The chromatographic method uses a uv detector with diode array (dad) as detection system, as mobile phase a mixture of H3PO4 0.1% in methanol and H3PO4 to 0.1% in water (48:52) and column chromatography C18 stabilized at 35 ¡ãC. The validated methodology was selective, linear, precise and accurate. The linearity was evaluated for concentrations between 4.8 and 24 mcg/mL. The developed methodology was used to carry out the study of stability of an extemporaneous suspension of phenobarbital used in the Clinic Country for the treatment of convulsions in pediatric patients.

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