Losartan potassium liquid formulation for paediatric hospital use: development and stability evaluation.

OBJECTIVES: This study aimed to develop a liquid oral formulation containing losartan potassium, an angiotensin II receptor antagonist drug used for its antihypertensive activity, and to perform a preliminary stability assessment under different temperatures and packages to ensure paediatric therapeutic adherence and facilitate the hospital routine. METHODS: A syrup containing losartan potassium (1.0 and 2.5 mg/mL) (excipients: potassium sorbate, sucrose (85%), water, citric acid and raspberry flavouring) was prepared. The packaging was carried out in amber polyethylene terephthalate (PET) and amber glass bottles (in triplicate) under the following conditions: (a) room temperature (15-30°C); (b) refrigeration (2-8°C); and (c) oven temperature (40°C) for 28 days. An analytical method by high performance liquid chromatography using a reverse-phase column was also developed and validated for quantitative determination of the drug in the formulations. RESULTS: The analytical method showed satisfactory linearity, detection and quantification limits, precision, accuracy and robustness. Samples at room temperature maintained content values between 90% and 110% for 7 days, while those stored under refrigeration maintained a homogeneous appearance and content between 90% and 110% for a period of 21 days. Values of pH stayed in a narrow range. Viscosity results were between 40.1 and 49.2 centipoise (cp) for glass bottles and 42.4 and 54.7 cp for PET bottles. CONCLUSIONS: A simple and economical losartan potassium liquid formulation was produced and was shown to be stable under refrigeration for 21 days in both PET and glass packages.

Stability Study of a Compounded Sublingual Buprenorphine Solution for Neonatal Opioid Withdrawal Syndrome.

OBJECTIVE: Sublingual (SL) buprenorphine is a cornerstone of care in the treatment of adult opioid use disorder. Recent studies have demonstrated its advantages in the management of neonatal opioid withdrawal syndrome (NOWS). Commercially available SL tablets and transdermal patches are not amenable to neonatal use, and published compounding formulas of SL solutions contained undesirable excipients, including ethanol, sugars, and preservatives. The objective of this research is to explore the stability of a novel SL buprenorphine formulation free of alcohol, sugars, and preservatives. METHODS: A 0.075 mg/mL buprenorphine solution was prepared by diluting the commercial injectable solution with normal saline and packaged into polyethylene terephthalate amber prescription bottles and polypropylene amber oral syringes and stored in refrigeration. Quality assessments were conducted by visual, pH, and high-performance liquid chromatography (HPLC) analysis immediately after preparation, and at 7 and 14 days of storage. RESULTS: There were neither visual nor pH changes detected through 14 days. HPLC analysis indicated that all samples retained >99% initial buprenorphine concentration. Drug concentration increased slightly in the oral syringe after day 7, probably due to moisture loss. No degradation peaks were observed in chromatograms. CONCLUSIONS: This novel buprenorphine is free of alcohol, sugar, and preservatives, and it may offer a significant safety advantage for NOWS patients. Additional clinical studies are recommended to verify the bioavailability and efficacy of this formulation.

Pharmaceutical evaluation of compounded furosemide capsules and excipient performance

Abstract Compounding pharmacies play an important role not only in compounding personalized formulations, but also preparing drugs at the same concentration and dosage as those from commercial manufacturers. The excipients used in compounding are generally standardized for many drugs, however they do not consider the intrinsic properties, such as the poor water solubility, of each substance. The excipient performance of commercially available compounded furosemide capsules in 7 compounding pharmacies from Manaus was evaluated and compared them to the performance of the reference medicinal product (Lasix® tablets) and 2 batches of capsules made in-house (T2 and T4) with a standardized excipient. All batches were subjected to tests for weight variation, assay, uniformity of dosage units, disintegration and dissolution profile. Of the 7 different compound formulas acquired in the compounding pharmacies, only 2 passed all tests. Most formulas passed the tests for weight determination, disintegration time and assay, however batches from 2 establishments failed in regards to the uniformity of the content and 5 batches failed the dissolution test. The reference medicinal product was approved in all tests, as were the T2 capsules made in-house with drug-excipient ratio 1:2. These results confirm the importance of the excipient composition, especially for poorly soluble drugs.

Comparación y concordancia de las ecuaciones más recomendadas de estimación de filtrado glomerular para el diagnóstico de enfermedad renal crónica en una población de Lima, Perú

Objetivo: Determinar la correlación y concordancia de fórmulas recomendadas para calcular la tasa de filtración glomerular (TFG) con el aclaramiento de creatinina medido (Clcr) en una población hospitalaria peruana. Material y métodos: Estudio de correlación y concordancia de personas con estados diferentes de función renal. Fueron estudiados 175 pacientes agrupados según el Clcr: Grupo 1: valores mayores de 140, Grupo 2: entre 140 a 90, Grupo 3: entre 90 a 60 y Grupo 4 cuyos valores fueron menores de 60 ml/min/1,73 m2 de SC. Se excluyeron los pacientes obesos (IMC>29). En una junta de orina de 24 horas y una muestra de sangre matutina se midió el Clcr (normalizado a 1,73 m2 de superficie corporal). Las fórmulas consideradas fueron: Cockcroft y Gault, MDRD, CDK- EPI y una fórmula peruana propuesta por Vásquez. Se analizó la correlación de Pearson entre las diversas fórmulas consideradas y el Clcr medido y su concordancia mediante el estudio de Bland Altman, de las diversas fórmulas usando la diferencia entre el resultado de cada fórmula para cada sujeto estudiado y el Clcr medido. Resultados: Todas las fórmulas propuestas tuvieron buen grado de correlación con el Clcr pero la fórmula CKD-EPI mostró importante imprecisión. Las fórmulas de Vásquez y MDRD mostraron leves diferencias favorables en pacientes con Clcr<60 ml/min. Conclusión: Recomendamos en nuestra población el uso de cualquiera de las fórmulas propuestas excepto CKD-EPI.

SUMMARY Objective: To determine the correlation and agreement between the most frequently used formulas estimate the glomerular filtration rate (GFR) and the measured Creatinine Clearance (CrCl), in a Peruvian population. Methods : Study of correlation and agreement in a population with different stages of renal function. 175 patients were included, grouped by CrCl: Group 1: higher than 140, Group 2: between 140 and 90, Group 3: Between 90 and 60, Group 4: less than 60 ml/min/1,73 m2 . Height and weight were measured to calculate body mass index (BMI). Obese patients (BMI>29) were excluded. Using a 24-hour urine collection and a serum creatinine sample, creatinine clearance was measured (normalized for 1.73 m2 of body surface). Formulas considered for analysis were: Cockroft and Gault, MDRD, CKD-EPI and a Peruvian formula proposed by Vásquez. Correlation was analyzed by Pearson coefficient between studied formulas and the measured CrCl; and its agreement was studied by Bland Altman analysis using the difference between the result obtained by each formula and the measured CrCl. Results : All studied formulas showed an acceptable degree of correlation but CKD-EPI formula had considerable imprecision. The formulas by Vásquez and MDRD showed slightly favorable differences in patients with CrCl<60 ml/min. Conclusion : We recommend the use of any of the studied formulas with exception of CKD-EPI in our population.

Atividades farmacológicas da manteiga de bacuri (Platonia insignis Mart): revisão integrativa / Pharmacological actions of bacuri butter (Platonia insignis Mart): an integrative review

RESUMO Objetivo identificar as atividades farmacológicas da manteiga de bacuri (Platonia insignis Mart.). Métodos revisão integrativa, realizada nas bases de dados Literatura Latino-americana e do Caribe em Ciências da Saúde, Cumulative Index to Nursing and Allied Health Literature, EMBASE, MEDLINE/PubMed, Web of Science, Cochrane Library e SCOPUS, sem delimitação temporal e de idioma. A seleção se constituiu de 13 ensaios pré-clínicos. A avaliação das informações ocorreu de forma descritiva, confrontando com os achados pertinentes. Resultados observou-se que 50,0% das publicações foram indexadas na MEDLINE/PubMed, maioria das publicações ocorreram na Inglaterra (61,5%), seguidas do Brasil e dos Estados Unidos, ambos com 13,3%. Destaca-se que 100,0% dos artigos foram ensaios pré-clínicos; atividades farmacológicas para antioxidante (38,4%) e antileishmanicidas (30,7%). Registrou-se que 38,4% dos ensaios apresentaram testes de toxicidade. Conclusão a manteiga de bacuri (Platonia insignis Mart.) apresentou atividades farmacológicas em ensaios pré-clínicos, como antioxidantes, antileshimaniose, anticonvulsivante e cicatrização de feridas.

ABSTRACT Objective to identify the pharmacological activities of bacuri butter (Platonia insignis Mart.). Methods an integrative review, carried out in the databases of Latin American and Caribbean Literature in Health Sciences, Cumulative Index to Nursing and Allied Health Literature, EMBASE, MEDLINE/PubMed, Web of Science, Cochrane Library and SCOPUS, without the time and language restriction. The selection consisted of 13 pre-clinical trials. The information assessment descriptively took place, comparing with the pertinent findings. Results it was observed that 50.0% of the publications were indexed in MEDLINE/PubMed, most publications were from England (61.5%), followed by Brazil and the United States, both with 13.3%. It is noteworthy that 100.0% of the articles were pre-clinical trials; pharmacological activities for antioxidants (38.4%) and antileishmanicides (30.7%). It was found that 38.4% of the trials presented toxicity tests. Conclusion bacuri butter (Platonia insignis Mart.) Showed pharmacological activities in pre-clinical trials, such as antioxidants, antileshimaniasis, anticonvulsant and wound healing.

A Week of Oral Terbinafine Pulse Regimen Every Three Months to Treat all Dermatophyte Onychomycosis.

Terbinafine has proved to treat numerous fungal infections, including onychomycosis, successfully. Due to its liver metabolization and dependency on the cytochrome P450 enzyme complex, undesirable drug interaction are highly probable. Additionally to drug interactions, the treatment is long, rising the chances of the appearance of side effects and abandonment. Pharmacokinetic data suggest that terbinafine maintains a fungicidal effect within the nail up to 30 weeks after its last administration, which has aroused the possibility of a pulse therapy to reduce the side effects while treating onychomycosis. This study's goal was to evaluate the effectiveness of three different oral terbinafine regimens in treating onychomycosis due to dermatophytes. Sixty-three patients with onychomycosis were sorted by convenience in three different groups. Patients from group 1 received the conventional terbinafine dose (250 mg per day for 3 months). Group 2 received a monthly week-long pulse-therapy dose (500 mg per day for 7 days a month, for 4 months) and group 3 received a 500 mg/day dose for 7 days every 3 months, totaling four treatments. There were no statistical differences regarding the effectiveness or side effects between the groups. Conclusion: A quarterly terbinafine pulse regimen can be a possible alternative for treating onychomycosis caused by dermatophytes.

Preformulation of a liquid dosage formulation of captopril for pediatric use: drug-excipient compatibility and stability studies

Currently, medications used in children are typically modified from pharmaceutical dosage forms designed for adults. Captopril is widely adapted to liquid formulations for use in hospitals. Its stability in the aqueous medium is reduced since it undergoes oxidation producing captopril disulfide (its main metabolite). The aim of this formulation study was to suggest favorable conditions for the development of a stable captopril formulation. The compatibility between the drug and excipients was evaluated by differential scanning calorimetry analysis (DSC). For studies in solution, different formulations were prepared according to a factorial design varying EDTA concentration, water purity and pH. The resultant formulations were stored at 60°C and analyzed over a twelve-day period using HPLC. The DSC curves obtained suggested, although not conclusive to elucidation, interactions of captopril with citric acid and sucralose. The stability study of these solutions revealed that the variables significantly influenced captopril content, which degraded at zero order kinetics and rates differing by a factor of up to 7 times, where pH proved the most influential factor. Interactions between variables were observed. Therefore, development of a stable captopril formulation is feasible provided EDTA and a buffering agent is used at suitable concentrations (0.08% and pH 3.85).

Evaluation of the impact that the changes in tuberculosis treatment implemented in Brazil in 2009 have had on disease control in the country / Avaliação do impacto das mudanças do tratamento da tuberculose implantadas em 2009 no controle da tuberculose pulmonar no Brasil

ABSTRACT Objective: To analyze the impact that the 2009 changes in tuberculosis treatment in Brazil had on the rates of cure, tuberculosis recurrence, mortality, treatment abandonment, and multidrug-resistant tuberculosis (MDR-TB). Methods: An ordinary least squares regression model was used in order to perform an interrupted time series analysis of secondary data collected from the Brazilian Tuberculosis Case Registry Database for the period between January of 2003 and December of 2014. Results: The 2009 changes in tuberculosis treatment in Brazil were found to have no association with reductions in the total number of cases (β = 2.17; 95% CI: −3.80 to 8.14; p = 0.47) and in the number of new cases (β = −0.97; 95% CI: −5.89 to 3.94; p = 0.70), as well as having no association with treatment abandonment rates (β = 0.40; 95% CI: −1.12 to 1.93; p = 0.60). The changes in tuberculosis treatment also showed a trend toward an association with decreased cure rates (β = −4.14; 95% CI: −8.63 to 0.34; p = 0.07), as well as an association with increased mortality from pulmonary tuberculosis (β = 0.77; 95% CI: 0.16 to 1.38; p = 0.01). Although there was a significant increase in MDR-TB before and after the changes (p < 0.0001), there was no association between the intervention (i.e., the changes in tuberculosis treatment) and the increase in MDR-TB cases. Conclusions: The changes in tuberculosis treatment were unable to contain the decrease in cure rates, the increase in treatment abandonment rates, and the increase in MDR-TB rates, being associated with increased mortality from pulmonary tuberculosis during the study period. Keywords: Tuberculosis, pulmonary/epidemiology; Tuberculosis, pulmonary/drug therapy; Tuberculosis, pulmonary/mortality; Interrupted time series analysis; Drug resistance, multiple; Drug compounding.

RESUMO Objetivo: Analisar o impacto das mudanças do tratamento da tuberculose implantadas no Brasil em 2009 no número de casos de cura, de recidiva, de óbitos, de abandono e de tuberculose multirresistente (TBMR). Métodos: Foi realizada uma análise de séries temporais interrompida utilizando o modelo de regressão pelo método dos mínimos quadrados ordinários a partir de dados secundários coletados do Sistema de Informação de Agravos de Notificação da Tuberculose entre janeiro de 2003 e dezembro de 2014. Resultados: A análise mostrou independência entre as mudanças do tratamento e a redução do número total de casos (β = 2,17; IC95%: −3,80 a 8,14; 189 p = 0,47), a redução do número de novos casos (β = −0,97; IC95%: −5,89 a 3,94; p =190 0,70) e do abandono do tratamento (β = 0,40; IC95%: 199 −1,12 a 1,93; p = 0,60). Demonstrou ainda tendência à associação com a diminuição da cura (β = −4,14; IC95%: −8,63 a 0,34; p = 0,07) e associação com aumento da mortalidade por tuberculose pulmonar (β = 0,77; IC95%: 0,16 a 1,38; p = 0,01). A TBMR aumentou significativamente tanto no período anterior quanto no período posterior às mudanças do tratamento (p < 0,0001), embora de forma independente da intervenção (β = 0,13; IC95%: −0,03 a 0,29; p = 0,12). Conclusões: As mudanças no tratamento não impediram nem a diminuição na taxa de cura e nem o aumento do abandono e da TBMR; por outro lado, se associaram ao aumento de óbitos por tuberculose pulmonar durante o período do estudo.

Predesigned labels to prevent medication errors in hospitalized patients: a quasi-experimental design study. / Etiquetas prediseñadas para prevenir errores de medicación en pacientes hospitalizados: estudio cuasi-experimental.

INTRODUCTION: Our institution implemented the use of pre-designed labeling of intravenous drugs and fluids, administration routes and infusion pumps of to prevent medication errors. OBJECTIVE: To evaluate the effectiveness of predesigned labeling in reducing medication errors in the preparation and administration stages of prescribed medication in patients hospitalized with invasive lines, and to characterize medication errors. METHODS: This is a pre/post intervention study. Pre-intervention group: invasively administered dose from July 1st to December 31st, 2014, using traditional labeling (adhesive paper handwritten note). Post-intervention group: dose administered from January 1st to June 30th, 2015, using predesigned labeling (labeling with preset data-adhesive labels, color- grouped by drugs, labels with colors for invasive lines). Outcome: medication errors in hospitalized patients, as measured with notification form and record electronics. Tabulation/analysis Stata-10, with descriptive statistics, hypotheses testing, estimating risk with 95% confidence. RESULTS: In the pre-intervention group, 5,819 doses of drugs were administered invasively in 634 patients. Error rate of 1.4 x 1,000 administrations. The post-intervention group of 1088 doses comprised 8,585 patients with similar routes of administration. The error rate was 0.3 x 1,000 (p = 0.034). Patients receiving medication through an invasive route who did not use predesigned labeling had 4.6 times more risk of medication error than those who had used predesigned labels (95% CI: 1.25 to 25.4). The adult critically ill patient unit had the highest proportion of medication errors. The most frequent error was wrong dose administration. 41.2% produced harm to the patient. CONCLUSIONS: The use of predesigned labeling in invasive lines reduces errors in medication in the last two phases: preparation and administration.

INTRODUCCIÓN: La seguridad en la administración de medicamentos requiere sistemas de prevención de errores. Para prevenirlos, se implementó como estrategia el uso de un etiquetado prediseñado de medicamentos y fluidos intravenosos de las vías de administración y bombas de infusión. OBJETIVO: Evaluar la efectividad del etiquetado prediseñado en la disminución de errores de medicación en las fases de preparación y administración, en pacientes hospitalizados con vías invasivas. Además se busca caracterizar los errores de medicación. MÉTODOS: Estudio pre y post intervención. Grupo pre intervención: dosis de medicamentos administradas invasivamente entre el 1 de julio y el 31 de diciembre de 2014, utilizando etiquetado tradicional (papel adhesivo manuscrito). Grupo intervención: dosis de medicamentos administradas entre el 1 de enero y el 31 de junio de 2015 utilizando etiquetado prediseñado (etiquetas adhesivas con datos preestablecidos, etiquetas de colores agrupadas según fármacos, etiquetas de colores para líneas invasivas). Variable respuesta: errores de medicación en pacientes hospitalizados medido según formulario de notificación y ficha electrónica. Tabulación/análisis: Stata-10, con estadística descriptiva, test de hipótesis y estimación de riesgo con 95% de confianza. RESULTADOS: Grupo pre intervención de 5819 dosis de medicamentos por vía invasiva en 634 pacientes. Tasa de error de 1,4 por 1000 administraciones. Grupo post intervención de 8585 administraciones por igual vía en 1088 pacientes. Tasa de error 0,3 por 1000 (p=0,034). Los pacientes que recibieron medicamentos por vía invasiva y no utilizaron etiquetado prediseñado tuvieron 4,6 veces más riesgo de sufrir un error de medicación que aquellos con etiquetado prediseñado (intervalo de confianza 95%; 1,25 a 25,4). La unidad de paciente crítico adulto presentó la mayor proporción de errores. El error más frecuente fue la administración de dosis incorrecta. El 41,2% produjo algún tipo de daño al paciente. CONCLUSIONES: El uso de etiquetado prediseñado de vías y líneas invasivas contribuye a disminuir los errores de medicación en las dos últimas fases, preparación y administración.

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.