Felipe L. Lopez

Formulation approaches to pediatric oral drug delivery: benefits and limitations of current platforms

Introduction: Most conventional drug delivery systems are not acceptable for pediatric patients as they differ in their developmental status and dosing requirements from other subsets of the population. Technology platforms are required to aid the development of age-appropriate medicines to maximize patient acceptability while maintaining safety, efficacy, accessibility and affordability. Areas covered: The current approaches and novel developments in the field of age-appropriate drug delivery for pediatric patients are critically discussed including patient-centric formulations, administration devices and packaging systems. Expert opinion: Despite the incentives provided by recent regulatory modifications and the efforts of formulation scientists, there is still a need for implementation of pharmaceutical technologies that enable the manufacture of licensed age-appropriate formulations. Harmonization of endeavors from regulators, industry and academia by sharing learning associated with data obtained from pediatric investigation plans, product development pathways and scientific projects would be the way forward to speed up bench-to-market age appropriate formulation development. A collaborative approach will benefit not only pediatrics, but other patient populations such as geriatrics would also benefit from an accelerated patient-centric approach to drug delivery.

Patient centric formulations for paediatrics and geriatrics: Similarities and differences

Paediatrics and geriatrics both represent highly heterogenous populations and require special consideration when developing appropriate dosage forms. This paper discusses similarities, differences and considerations with respect to the development of appropriate medicine formulations for paediatrics and geriatrics. Arguably the most significant compliance challenge in older people is polypharmacy, whereas for children the largest barrier is taste. Pharmaceutical technology has progressed rapidly and technologies including FDCs, multi-particulates and orodispersible dosage forms provide unprecedented opportunities to develop novel and appropriate formulations for both old and new drugs. However, it is important for the formulation scientists to work closely with patients, carers and clinicians to develop such formulations for both the paediatric and geriatric population.

Acceptability of placebo multiparticulate formulations in children and adults

Patient acceptability is an important consideration in the design of medicines for children. The aim of this study was to investigate acceptability of multiparticulates in healthy children and adults. A randomised, single-blind acceptability testing was performed involving 71 children (4–12 years) and 61 adults (18–37 years). Each participant received three 500 mg samples of microcrystalline cellulose pellets administered on a medicine spoon with water at 5–10 minutes intervals. Acceptability was measured based on voluntary intake of the samples, facial expressions, ratings on hedonic scales and reported willingness to take multiparticulates everyday as a medicine. Multiparticulates were voluntarily swallowed by 92% of children and 100% of adults. However, palatability issues were identified, with emphasis on textural aspects. Grittiness perception received negative ratings on hedonic scales by 60% of children and 51% of adults. Researcher observations revealed that 72% of children and 42% of adults displayed negative facial expressions towards the samples. Children reported their willingness to take multiparticulates as a medicine in 30% of the cases, compared to 74% in adults. This study demonstrates that multiparticulates may be a suitable formulation platform for children and adults, although palatability concerns have been highlighted. Additional work is required to define acceptability criteria and to standardise methodologies.

The effect of administration media on palatability and ease of swallowing of multiparticulate formulations

Graphical abstract Figure. No Caption available. ABSTRACT Multiparticulate formulations based on pellets, granules or beads, could be advantageous for paediatrics, geriatrics and patients with swallowing difficulties. However, these formulations may require suitable administration media to facilitate administration. The aim of this work was to investigate the effect of administration media properties on palatability and ease of swallowing of multiparticulates. A range of vehicles were developed using xanthan gum (XG) and carboxymethyl cellulose (CMC) as model hydrocolloids. Such vehicles were prepared at three consistency levels (Level 1 – ‘syrup’, Level 2 – ‘custard’ and Level 3 – ‘pudding’) to investigate the effect of viscosity on their performance as administration media. A randomised, single‐blind sensory evaluation study was carried out in thirty healthy adult volunteers using microcrystalline cellulose pellets as model multiparticulates, dispersed in the hydrogels (and water as control) at a concentration of 250 mg in 5 ml. Samples were evaluated using 5‐point scales. The use of hydrogels as administration media improved a range of sample attributes compared to water formulations, including appearance, taste, mouthfeel, ease of swallowing and residue in the mouth (all improved by ca. 0,5 points) and oral grittiness perception (improved by ca. 1 point). Polymeric hydrogels thickened to medium consistency (Level 2, XG 0.5% and CMC 1.0% w/v) demonstrated the best performance.