Mini-Tablets: A Valid Strategy to Combine Efficacy and Safety in Pediatrics
In the treatment of pediatric diseases, mass-produced dosage forms are often not suitable for children. Commercially available medicines are commonly manipulated and mixed with food by caregivers at home, or extemporaneous medications are routinely compounded in the hospital pharmacies to treat hospitalized children. Despite considerable efforts by regulatory agencies, the pediatric population is still exposed to questionable and potentially harmful practices.
When designing medicines for children, the ability to fine-tune the dosage while ensuring the safety of the ingredients is of paramount importance. For these purposes solid formulations may represent a valid alternative to liquid formulations for their simpler formula and more stability, and, to overcome the problem of swelling ability, mini-tablets could be a practicable option.
This review deals with the different approaches that may be applied to develop mini-tablets intended for pediatrics with a focus on the safety of excipients. Alongside the conventional method of compression, 3D printing appeared particularly appealing, as it allows to reduce the number of ingredients and to avoid both the mixing of powders and intermediate steps such as granulation. Therefore, this technique could be well adaptable to the daily galenic preparations of a hospital pharmacy, thus leading to a reduction of the common practice of off-label preparations.
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About this article: Zuccari, G.; Alfei, S.; Marimpietri, D.; Iurilli, V.; Barabino, P.; Marchitto, L. Mini-Tablets: A Valid Strategy to Combine Efficacy and Safety in Pediatrics. Pharmaceuticals 2022, 15, 108. https://doi.org/10.3390/ph15010108
Excerpt on Excipients from the publication
Appropriate Excipients for Pediatrics
In principle, almost all drug formulations contain excipients that have been used for many years and are considered to have a generally regarded as safe (GRAS) status. They are described in monographs in various pharmacopeias and released with certificates of analyses, performed according to monograph test methods, that warrant their quality. In any case, the specifications embedded in the monographs are intended to cover use in adults and not in children. Consequently, although significant differences in pharmacokinetics and pharmacodynamics exist between the two patient populations, it is common practice to assume that excipients, which did not cause adverse reactions in adults, are safe also in neonates and/or children. In recent years, awareness that some excipients are less well tolerated in children, especially in neonates whose physiological systems are still undergoing development, has become known for the intervention of the regulatory authorities. In fact, some neonates may not be able to clear an excipient with the same rate as adults, as in cases of phenylketonuria. Therefore, not only the choice of the most suitable formulation but also the selection of excipients represent key factors in the development of adequate pediatric dosage forms. In the EMA guideline, it is stated how the selection of a safe excipient can be performed [9]. In projecting a new formulation, the EMA guideline suggests that a certain excipient should be chosen by drawing on the sources listed below in hierarchical order. Commission, ICH, and EMA guidelines
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CHMP scientific opinions
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Already authorized in pediatric medicines with known quantitative composition
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Included in the European Food Legislation or Included in EFSA opinions
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Other sources such as the expert committee on food additives (JECFA), indexed
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Literature, or in-house scientific evidence