Mini-Tablets: A Valid Strategy to Combine Efficacy and Safety in Pediatrics

Abstract

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.

Keywords: European Paediatric Regulation; excipients; flexible dose; medicines for children; mini-tablets; pediatric formulations; solid dosage forms.

Figure 1

The European path of pediatric formulations.

Figure 2

Number of publications per year of the last 20 years according to Scopus.

Figure 3

Main activities of excipients reported in Table 1 and their frequency (DES = dispersing, emulsifier, suspending).

Figure 4

The main usability issues and concerns of common pediatric dosage forms.

Figure 5

Multiple-tip punch with the correspondent die for mini-tablet manufacturing (a,b); typical dimension of mini-tablets (c).

Figure 6

Distribution of the main typologies of the developed mini- and micro-tables formulations (a); (b) average DT values of oro-dispersible, uncoated/oro-dispersible and uncoated micro- and mini-tablet formulation reported in Table 5.

Figure 7

Pediatric preparations developed and dispensed by the G. Gaslini Hospital Pharmacy.