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.

A Study on Pharmacokinetics of Acetylsalicylic Acid Mini-Tablets in Healthy Adult Males—Comparison with the Powder Formulation

“…Furthermore, Klingmann et al reported that in children aged 6 months and older, administration of 25 or more mini-tablets was well tolerated, feasible, safe, and superior to equivalent doses of syrup [ 19 ], suggesting the possibility that mini-tablets could be used for oral medications at higher doses. The results of these studies support the transition from syrups to small-solid dosage forms for children of all ages, as advocated by the WHO [ 15 ].…”

“…Mini-tablets have garnered interest as a novel form of solid medication for children. They employ the same manufacturing techniques, equipment, and formulation as their adult counterparts and are less prone to taste or texture issues [ 15 ]. Klingmann et al compared the acceptability and ability to swallow a syrup formulation and an uncoated mini-tablet (2 mm diameter) in 306 children aged 6 months to 6 years and found that the mini-tablet was superior [ 16 ].…”

Acceptability, Swallowability, Palatability, and Safety of Multiple Film-Coated Mini-Tablets in Children Aged ≥2–<7 Years: Results of an Open-Label Randomised Study

“…Achieving adequate dosing of medicines in the paediatric population while ensuring safety is challenging [ 1 ], as children are often unable to ingest standard-sized solid dose formulations and find many oral medications unpalatable [ 1 , 2 ]. In addition, a drug’s pharmacokinetic profile may be influenced by age and body weight, highlighting a potential need for flexible dosing for paediatric populations [ 1 ]. There has been a great effort over the past two decades to develop age-appropriate formulations of medicines for paediatric use [ 1 , 2 , 3 , 4 ].…”

“…In addition, a drug’s pharmacokinetic profile may be influenced by age and body weight, highlighting a potential need for flexible dosing for paediatric populations [ 1 ]. There has been a great effort over the past two decades to develop age-appropriate formulations of medicines for paediatric use [ 1 , 2 , 3 , 4 ]. While conventional formulations, such as syrups, are commonplace in paediatric medicine, these formulations can sometimes have disadvantages, such as drug instability, poor palatability, the uncontrolled release of active compounds, inconsistent dosing due to incomplete swallowing, and limited knowledge of which excipients are safe for use in the paediatric population [ 5 , 6 ].…”

“…A shift towards small solid dosage forms over liquid formulations has been proposed by the European Medicines Agency (EMA) (in 2014) [ 4 ] and the World Health Organization (WHO) (in 2008) [ 7 ]. Specially designed mini-tablets could help to overcome these challenges, and they are also suited for the administration of a wide range of doses [ 1 ]. Mini-tablets have additional advantages of low costs and greater ease of use (i.e., mini-tablets are simply counted and there is no need to measure volumes or reconstitute) and transport [ 8 ].…”