Time to change the paradigm of children’s medicines from liquid formulations to flexible solid oral dosage forms

Abstract

Time to change the paradigm of children's medicines from liquid formulations to flexible solid oral dosage formsWorldwide, people prefer a liquid formulation when paediatric medicines have to be given orally. The syrups and suspensions can be dosed flexibly by increasing the volume with age and weight of the child. We believe that young children can swallow liquids better than solids and prefer to take a sweet tasting liquid medicine. Simply liquid medicines are what children choose if they are given the chance -or at least that is what we adults think. When new innovative medicines are developed for use in children, the global pharmaceutical industry usually develops a liquid formulation for children if the medicine is to be given orally. In rich countries liquid formulations for oral medicines continue to be the rule.In resource limited settings (RLS) age appropriate paediatric formulations for children are not commonly available [1,2]. If what the pharmaceutical industry develops for children are liquid formulations, then one could think that the lack of paediatric medicines in RLS could be just a consequence of the general lack of availability of children's medicines in those settings. But what if the domination of liquid oral formulations as the perceived first choice for children is in fact also a cause and not only a consequence of the problem of poor availability of age appropriate paediatric medicines in RLS? Indeed, liquid oral formulations possess problematic characteristics particularly relevant in RLS [1]. Logistics of liquid oral formulations are complicated by increased bulk and commonly need cold-chain, problems for both the professional of bulk transport, and for the family who has to carry the child's medicines home. From a pharmaceutical development and manufacturing point of view, liquid medicines are problematic in many ways. Taste-masking is challenging, liquid formulations require more excipients than solid ones, and some excipients may not be suitable for children. Importantly, liquid formulations are more expensive to produce than solid dosage forms. The higher costs of production and logistics make liquid medicines more expensive than medicines in solid formulations. A switch to solid oral paediatric formulations would be a way to improve availability of paediatric medicines, if only the children would accept them and be able to swallow them.May be we should ask the children! That is exactly what we did in Helsinki in 1999 when we interviewed 150 children who were 3-7 years old andThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Drug Formulations: Standards and Novel Strategies for Drug Administration in Pediatrics

“…These modern drug formulations are often considered as the dosage forms of choice . Some authors claim a required shift of paradigm from the previously favored liquid formulations to the novel flexible solid dosage forms . However, solid dosage forms might not serve for drug administration to neonates, which are a special subpopulation in this context .…”

Medicines for children: Rationale and recent advances

“…Hence, evidence is emerging on suitable formulations and dosing devices (for liquid formulations) as well. In September 2016, the Ceylon Medical Journal published a leading article on paediatric oral formulations, authored by Professor Kalle Hoppe, one of the pioneers in paediatric clinical pharmacology (40). It was an excellent, timely article which should be instrumental in improving availability of child friendly formulations in Sri Lanka.…”

“…Traditionally, liquid formulations, namely syrups and suspensions, are favored for paediatric oral use. However, many problems are recognized with these formulations, some of which are particularly relevant to RLSs [32,40]. Such problems include (i) expensive manufacturing processes (ii) difficulty in taste masking (iii) logistics of transport and storage (iv) requirement of refrigerator to store the reconstituted suspension (v) requirement of clean water to reconstitute dry powders (vi) the necessity to have more excipients, some of which may be not suitable for children and (vii) poor stability in a tropical climate.…”

“…Moving to solid oral paediatric formulations (flexible solid oral dosage forms) appears to be the most sensible solution to address the above problems. Such alternative flexible solid oral dosage forms include multiparticulate formulations (minitablets, sprinkles and granules), orodispersible formulations (orodispersible minitablets, disintegrating tablets, oral strips, buccal wafers, medicated lollipops) and dispersible tablets [40,41,42,43].…”

“…Studies have documented the acceptability, swallowability, palatability and accuracy of the dose delivery and bioavailability of these flexible solid oral dosage forms for children [40,45]. Most of them retain the advantages of traditional solid oral dosage forms (tablets and capsules), like stability, taste masking and ease of transport and require no manipulation in the field.…”