Stability of sulfadiazine sugar-free oral suspensions for the treatment of congenital toxoplasmosis

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.

Comparison and improvement of palatability for multisourced oral azithromycin suspension / 药学学报

Azithromycin dry suspension is one of the most commonly used drugs in pediatric clinic, but its taste masking has been difficult to achieve. 5 representative products of azithromycin dry suspension were chose to compare their tastes both using electronic tongue and human sensory evaluation methods, and there existed the differences of bitterness, later bitterness, graininess, and adhesion among these products. Raman micro-imaging was used to determine the difference in taste mainly due to different prescription ingredients and manufacturing techniques. Through mixing the dry suspensions with alkaline mixing solvent, the bad taste of each product was masked after evenly dispersing in the solvent, and their tastes were all close to the taste of the solvent. In the future, it is planned to investigate the stability and bioavailability of the solvent preparations, and then to give the medication suggestion of solvent preparation after ensuring their efficacy.

Stability and taste evaluation of two kinds of oral solvent after extemporaneous compounding / 药学学报

A flavoring agent and a suspension agent were prepared for extemporaneous compounding. The stability of the two agents before and after drug loading was investigated, and the taste of the suspension after extemporaneous compounding was evaluated by electronic tongue technology. The two agents remained stable under the conditions of influence factor test, accelerated test and long-term test. The appearance properties of the two agents did not change. The relative density of the flavoring agent was maintained at 1.053-1.075, and the pH was stable at 4.2-4.5. The relative density of the suspension agent was maintained at 0.999-1.022, and the pH was stable at 4.0-4.5. Seven kinds of drugs, including warfarin sodium tablets and spironolactone tablets, were mixed with these two oral solvents, and the content uniformity and stability were detected respectively. The results showed that the preparations could be evenly dispersed and the physical and chemical properties were stable. The results of taste evaluation showed that in captopril group and chloral hydrate group, the flavoring agent had the best effect on taste correction. In warfarin sodium group, rifampicin group, spironolactone group, vitamin B1 group and vitamin B2 group, the blending agents had the best effect on taste correction.

Subjetividade literária / Literary subjectivity

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.

Preparation of extemporaneous oral liquid in the hospital pharmacy

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.

Quality and stability of oral extemporaneous formulations developed from commercial tablets containing spironolactone / Desenvolvimento e estudo de estabilidade de formulações extemporâneas de uso oral a partir de comprimidos comerciais contendo espironolactona

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...

Desarrollo y validación de una metodología analítica por HPLC-DAD para la cuantificación de Warfarina Sódica en una preparación extemporánea / Development and validation of an analytical method by HPLC-DAD for quantification of Warfarin Sodium in an extemporaneous preparation

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.

Physical, chemical, and microbiological stability of extemporaneous furosemide suspensions.

Background: Furosemide is a potent diuretic used in treatment of oedematous states associated with cardiac, renal, and hepatic failure and the treatment of hypertension. In Thailand, no liquid formulation of furosemide is commercially available for pediatric administration and for adult who cannot swallow furosemide tablets. Objective: Prepare extemporaneous furosemide suspensions from commercial furosemide tablets using two compounded suspending vehicles, and determine the physical, chemical, and microbiological stability of these preparations. Methods: Two formulations of extemporaneous furosemide suspensions were prepared from commercially available furosemide 40-mg tablets using two compounded suspending vehicles. The final concentration of furosemide in each formulation was 2 mg/mL. Three samples of each formulation were stored in glass bottles protected from light, and kept at three controlled temperature, 4?2?C, room temperature (30?2?C), and 45?C. A sample was removed from each bottle immediately after preparation and at 7, 14, 30, 45, and 60 days. The stability-indicating highperformance liquid chromatography was used to analyze for furosemide. The pH was measured. The physical and microbiological properties of these formulations were evaluated after storage for two months. The stability of furosemide suspensions was determined by calculating the percentage of the initial concentration remaining on each test day. Stability was defined as retention of at least 90% of the initial concentration. Results: At least 93% of the initial furosemide concentration remained in both compounded furosemide suspensions for up to 60 days. There were no substantial changes in the appearance (color and consistency) or odor of both formulations. The pH values of both formulations kept at 4?2?C increased slightly, while the pH values of both formulations kept at 45?2?C decreased significantly compared with the initial pH value of both formulations. Both formulations maintained microbiologic stability for 60 days. Conclusion: Extemporaneously compounded furosemide suspensions, 2 mg/mL, were stable for at least 60 days when stored in glass bottles protected from light at three controlled temperatures. These compounded furosemide suspensions are better suited for administration to children and adults who cannot swallow furosemide tablets. They may provide an alternative in situations where the marketed suspension is unavailable.

Elaboração e avaliação de material educativo impresso para auxiliar na adesão medicamentosa de pacientes pediátricos pós-alta hospitalar / Development and evaluation of printed educational material to improve the medication compliance of pediatric patients after hospital discharge

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

Desarrollo y validación de una metodología analítica por HPLC para la cuantificación de fenobarbital en una suspensión extemporánea / Development and validation of an analytical method by hplc for quantification of phenobarbital in extemporaneous suspensions

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.