Objective: Develop a child-friendly Fixed Dose Combination (FDC) water-dispersible tablet for Tuberculosis (TB) treatment, with 50, 150 and 75 mg of isoniazid (INH), pyrazinamide (PZA) and rifampicin (RFP) respectively. This new formulation must contain the lowest possible number of excipients, all accepted for pediatrics, and fulfill all the pharmacopoeia requirements for this type of tablet (friability, disintegration time, fineness of dispersion and content uniformity).Significance: TB is an infectious disease which caused the death of 233,000 children in 2017. At present there is no adequate market dosage form available for children. There is, however, one in a prequalification phase by the World Health Organization but its composition contains some excipients which may not be suitable for pediatrics.Therefore, this new formulation would cover this therapeutic gap.Methods: A factorial design, based on 3 quantitative factors (compression force and concentration of AcDiSol® and Explosol®) at three levels each, was performed to elucidate their influence over disintegration time and friability. In addition, the influence of the press speed on disintegration time, friability, tensile strength, fineness of dispersion and content uniformity over the target tablet was tested. A stability test was done following ICH guideline for accelerated conditions.Results: A water-dispersible tablet was developed according to international recommendations in terms of excipients for pediatrics and meeting Ph. Eur. requirements.In addition, its production has been optimized to be elaborated at maximum eccentric press speed but maintaining quality requirements.Conclusion: A high-quality child-friendly FDC water-dispersible tablet was developed improving the treatment of TB in pediatric.

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OBJECTIVES Extemporaneous or magistral formulation of active pharmaceutical ingredients using traditional compounding techniques is a common practice when no commercial form is available for pediatrics. For this vulnerable group of patients, the formulation must be prepared with the minimum quantity and lowest proportion of excipients approved for pediatrics, avoiding the use of preservatives. Often the vehicles used for these preparations are dilutions of simple syrup with water. The objective of this study is to assess the effectiveness of antimicrobial preservation in simple syrup diluted with aqua conservans (conserved water), without propylene glycol or with a reduced proportion of parabens. METHODS The European Pharmacopoeia test of efficacy of antimicrobial preservation was applied to 5 trial vehicles prepared with simple syrup diluted with water. RESULTS Simple syrup is stable during 14 days. Vehicles prepared with simple syrup diluted with purified water did not meet the microbiological quality criteria, but when they are diluted with water that incorporates propylene glycol and parabens (aqua conservans), then they meet the criteria. In addition, if the water is prepared with parabens and without propylene glycol, the criteria for the dilution are met. Nevertheless, if the dilution is done with water prepared with an insufficient proportion of parabens to act as preservatives, the dilution does not meet the pharmacopoeia microbiological criteria. CONCLUSIONS Dilution of simple syrup (50:50 v/v) to prepare a vehicle for extemporaneous or magistral preparation is microbiologically safe when water with methylparaben and propylparaben is used in a proportion of 0.08% and 0.02% (w/w), respectively, avoiding the use of propylene glycol as a solvent and thus its toxic effects in pediatrics.

El Docentia es el modelo propuesto por ANECA, y asumido por las universidades españolas para la evaluación de la calidad docente. Uno de los problemas del modelo que se viene detectando es su escasa capacidad para diferenciar al profesorado entre las distintas categorías posibles, con un sesgo muy acentuado hacia la calificación de “Excelente”. Esto afecta al prestigio del modelo: primero, si la gran mayoría del profesorado es “Excelente”, no se verá reflejado el profesorado que realmente destaca sobre el conjunto y, segundo, afecta a su capacidad para orientar al profesorado hacia la mejora de su docencia. En el presente estudio examinamos la capacidad discriminativa del modelo en base a la experiencia de su implementación en la Universidad de La Laguna (Docentia-ULL). Hemos simulado el resultado de la evaluación cambiando el modelo en dos sentidos. Por un lado, los pesos de las dimensiones y sub-dimensiones, así como de los topes de cada criterio, para primar la valoración del compromiso del profesorado con la formación y la innovación educativa, frente al mero cumplimiento de las obligaciones docentes. Por otro lado, los resultados de satisfacción del alumnado y de los responsables académicos pasan a actuar como requisito independiente de los méritos del docente en la evaluación. Además, se ha elevado el mínimo necesario de estas dimensiones para obtener una valoración “Favorable”, “Muy Favorable” o “Excelente”. Los resultados mostraron que la disminución del peso en la evaluación de las obligaciones docentes frente a la formación e innovación produjo una distribución de la calificación del profesorado más centrada hacia las categorías intermedias. Además se compara con resultados reales obtenidos después de la implantación del modelo alternativo elegido a raíz de las simulaciones. Se discuten las implicaciones de este tipo de mejoras en la evaluación de la calidad docente y del desempeño del profesorado en la universidad española.

There is as yet no commercialized preparation for oral administration of flecainide acetate (FA) to children. In such cases, manipulation of commercial tablets is the usual practice in pharmacy services of hospitals and compounding pharmacies, to provide a suitable dosage form for this vulnerable pediatric population group. In this study, we have formulated FA as an oral solution, as an alternative to the suspension elaborated from commercial tablets. Due to this sensitivity of young patients, we have used the pure active pharmaceutical ingredient (API) and the lowest permitted levels of pediatric excipients. Despite being a highly soluble API, only one of the formulations appears as a transparent solution due to complete FA solubilization. The proposed formulation is physico-chemically and microbiologically stable and the mass and dose uniformity is appropriate for 30 days' storage at 25 °C.

(1) Background: First-line antituberculosis treatment in paediatrics entails the administration of Isoniazid, Pyrazinamide, and Rifampicin. This study examines the possibility of developing a combined dose liquid formulation for oral use that would facilitate dose adjustment and adherence to treatment for younger children. (2) Methods: The active pharmaceutical ingredients stability under in vitro paediatric digestive pH conditions have been checked. The samples were studied as individual or fixed combined paediatric dosages to determine the pH of maximum stability. The use of hydroxypropyl-β-cyclodextrin to improve Rifampicin solubility and the use of ascorbic acid to increase the stability of the formulation have been studied. (3) Results: Maximum stability of combined doses was determined at pH 7.4, and maximum complexation at pH 8.0. Taking this into account, formulations presented the minimum dose of two active pharmaceutical ingredients dissolved. The addition of ascorbic acid at 0.1% w/v enables the detection of a higher remaining quantity of both drugs after three days of storage at 5 °C. (4) Conclusions: a formulation which combines the minimum paediatric dosages dissolved recommended by WHO for Isoniazid and Rifampicin has been developed. Future assays are needed to prolong the stability of the formulation with the aim of incorporating Pyrazinamide to the solution.

Background: In 2020 the composition and procedure to elaborate a new formulation containing Isoniazid, Pyrazinamide and Rifampicin to treat tuberculosis in pediatric patients was published. The temperature and relative humidity in Tuberculosis-endemic countries are high, > 30ºC and > 70% respectively and thus these meteorological conditions required a new dosage form. The objective of this work is to register changes in tablet quality and stability over time when exposed to different storage conditions according to ICH. Method: Tablets were subjected to accelerated, long term and low relative humidity conditions. The effect of light was also tested. Quality was measured by evaluating weight changes tensile strength, disintegration time, and drug content. Hydrazine formation was also evaluated as it is considered a mutagenic degradation product. Results: Tablets stored at low relative humidity showed the best stability. There was no statistically significant difference between tablets exposed to or protected from light. Moreover, the formation of Hydrazine was not detected during stability studies. Conclusion: This new dosage form for treating Tuberculosis is stable and able to maintain its quality when appropriate storage conditions are used.