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A High-Demanding Strategy to Ensure the Highest Quality Standards of Oral Liquid Individualized Medicines for Pediatric Use

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Abstract

Individualized medicines for pediatrics are a useful alternative if there is no correct dosage marketed for this segment (easy to swallow, adequate volume and content, correct composition for pediatrics, good organoleptic properties, etc.). Its validation process must ensure quality testing: its content uniformity, physical (homogeneity after shaking), chemical, and microbiological stability. Some of these attributes are checked by the recommendations of European Pharmacopoeia (Ph. Eur.), International Conference of Harmonization (ICH), and National Formularies but others are not. The aim of this study is to develop a general high-demanding strategy to ensure the final quality of liquid dosage forms testing and developing standard operating processes (SOPs) for the elaboration of individualized oral liquid medicines for pediatric use. Furosemide was used as an example of the validation of an individualized liquid solution for pediatric use. Three SOPs were selected according to their composition and the recommendations of liquid dosage forms for pediatric use. Quality attributes according to National Formularies, Ph. Eur., and ICH were tested: pH, organoleptic properties, uniformity of mass of delivered dose from multidose containers, and chemical stability. In this study, a general high-demanding strategy was elaborated to validate oral liquid dosage forms, including validation of the analytical method used to test their quality. A second part focuses on the elaboration of liquid formulations for pediatrics with the highest standards of quality taking into account CQAs that were not contemplated by official compendial such as content uniformity and physical stability.

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Acknowledgments

This work was supported by a Research Project of Fundación CajaCanarias in Spain (BIO27). The authors are very grateful to the following for their collaboration: Instituto Tecnológico del Medicamento Individualizado (ITMI) and Comisión Nacional de Unificación de Criterios en Formulación Pediátrica. The authors also to thank Cajasiete and Universidad de La Laguna for their contribution with a predoctoral contract.

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Authors and Affiliations

  1. Programa Doctorado en Ciencias de la Salud, Universidad de La Laguna, La Laguna, Spain

    Javier Suárez-González

  2. Departamento Ingeniería Química y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de La Laguna, Entrada Campus Anchieta, 4, 38206, San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain

    Javier Suárez-González, Ana Santoveña-Estévez, Sofía Armijo-Ruíz, Aurora Castillo & José B. Fariña

  3. Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, La Laguna, Spain

    Javier Suárez-González, Ana Santoveña-Estévez & José B. Fariña

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  1. Javier Suárez-González
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  2. Ana Santoveña-Estévez
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  3. Sofía Armijo-Ruíz
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Correspondence to Javier Suárez-González.

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Suárez-González, J., Santoveña-Estévez, A., Armijo-Ruíz, S. et al. A High-Demanding Strategy to Ensure the Highest Quality Standards of Oral Liquid Individualized Medicines for Pediatric Use. AAPS PharmSciTech 20, 208 (2019). https://doi.org/10.1208/s12249-019-1432-x

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