Multiple possibilities, one decision
Pediatric formulation development usually starts with understanding the exact drug product (DP) requirements followed by subsequent benchmarking against the available formulation options as there is no such thing as one technology fits all. Before starting, the above evaluation sets the taste masking, the stability profile, the final representation, and the age range requirements. Considering these criteria, the best suited oral DP strategy can thereafter be selected for development.
Five oral dosage forms carry most pediatric programs, namely: oral liquids, orally disintegrating tablets, granules, multiparticulates and minitablets. No single option can be regarded as universally preferable. Each dosage form offers distinct benefits, but these are accompanied by corresponding limitations.
This post compares these five options and then sets out what Ardena runs for pediatric oral solid dosage development at its Somerset, New Jersey site. For the regulatory framing, age group definitions, excipient safety and palatability testing that sit underneath these choices, see our earlier post on age-appropriate pediatric formulations.
Pediatric dosage forms compared
| Dosage form | Advantages | Disadvantages |
|---|---|---|
| Oral liquids | Dose flexibility; ease of administration; ease of ingestion; well established acceptance for pediatric medicine; the most preferred form for newborns and infants | Taste masking challenges; stability issues; susceptible to microbial growth; requires preservatives; risk of dosing error during administration |
| Orally disintegrating tablets (ODT) | Precise dosing; improved stability; ease of ingestion; no water needed for administration | Sensitive to moisture; taste masking challenges; not preferred for newborns and children under 2 years |
| Granules | Dose flexibility; precise dosing; improved stability; multiple taste masking options; dispersed in liquid or sprinkled on food; unit dose presentation as capsules, sachets or stick-packs | Irregular particle shape creates mouthfeel challenges; risk of incomplete administration when mixed with food; not preferred for newborns and children under 1 year |
| Multiparticulates | Dose flexibility; precise dosing; improved stability; taste masking options; immediate and controlled release; sprinkled on food; unit dose presentation as capsules, sachets or stick-packs | Risk of incomplete administration when mixed with food; not preferred for newborns and children under 1 year |
| Minitablets | Dose flexibility; precise dosing; improved stability; taste masking options; immediate and controlled release; sprinkled on food; unit dose presentation as capsules, sachets or stick-packs | Mouthfeel challenges depending on minitablet size; risk of incomplete administration when mixed with food; not preferred for newborns and children under 2 years |
Three patterns are worth pulling out of that table.
The first is the trade between liquids and everything else. Liquids are the most accepted form in the youngest patients and the easiest to administer, but they carry the whole burden of aqueous formulation: microbial growth, preservative systems, physical and chemical stability, and dosing accuracy that depends on whoever is holding the syringe. Every solid form on the list improves stability and dosing precision; however, every one of them is incompatible with the youngest patient population of pediatric patients.
The second is that risk moves rather than disappears. Granules, multiparticulates and minitablets all solve dose accuracy at the point of manufacture, then reintroduce it at the point of administration, because a dose sprinkled onto food is only fully delivered if the child finishes the food.
The third is mouthfeel. Granules carry irregular particle shape and the mouthfeel challenge that comes with it. Minitablets have controlled geometry, but mouthfeel becomes a challenge again depending on the size of the minitablet. Multiparticulates may present a lower or more manageable mouthfeel challenge, depending on particle design and the delivery vehicle.
Taste masking sets the formulation approach
Taste masking is where the dosage form decision becomes a formulation decision. A bitter API in a liquid has few places to hide, which is one reason some of the solid forms carry the taste masking advantage in the comparison above. In granules, multiparticulates and minitablets, if coated, the drug can be enclosed before it ever comes into contact with the tongue.
Five approaches are available for pediatric formulation development at Somerset: viscosity modified formulations, particle coating, complexation with ion exchange resin, inclusion complexation with cyclodextrin, and microencapsulation. Having a range that wide matters, because the taste masking route has to fit both the molecule and the dosage form the program has already chosen, and a site that only runs one approach will steer every project towards it.
Note one limitation worth planning around. Electronic taste masking testing using an e-tongue is subcontracted rather than run in house.
Twin screw extrusion across the process toolbox
The process set at Somerset is built around twin screw platforms. Twin screw extrusion, twin screw dry granulation, twin screw wet granulation and twin screw melt granulation cover a wide span of pediatric feedstocks from a common equipment base, which matters when a program changes direction between granules and multiparticulates partway through development.
Alongside those sit extrusion spheronization, fluid bed coating, tablet compression and encapsulation, plus hot melt extrusion where a solvent-free amorphous route is the right answer for the molecule.
The practical value of that range is that the process does not dictate the dosage form. Spheronization and coating produce the multiparticulates. Compression produces the minitablets. Granulation produces the granules. The decision can stay a patient-driven one rather than a capability-driven one.
Sprinkle capsules and the presentation question
A pediatric formulation is not finished at the particle. It still has to reach the patient in a unit the caregiver can handle.
Sprinkle capsules are the presentation Ardena manufactures for pediatric programs at Somerset. They give a defined unit dose that opens onto soft food, which is what makes granules, multiparticulates and minitablets usable in children who cannot swallow an intact capsule. Sachets and stick-packs are also available as presentations, currently through subcontracting rather than in house.
Pediatric dosage forms at a US site
Somerset develops and manufactures granules, multiparticulates and minitablets for pediatric programs, with liquid formulation supported at preclinical stage. One commercial pediatric formulation is manufactured at the site for a large pharmaceutical company.
That last point is the one that is hard to match. Describing pediatric capability is common. Having taken a pediatric formulation through to commercial manufacture is not, and it is the difference between a site that can run the work and a site that has already run it at full scale. More on the facility itself is in our post on the Ardena Somerset site.
Subject Matter Experts
Iñaki Bueno
Formulation-Production & Maintenance Director
Iñaki Bueno is Formulation-Production and Maintenance Director at Ardena Pamplona. He is a pharmacist with more than 30 years of experience in pharmaceutical development, specializing in formulation design, process scale-up, and GMP manufacturing of innovative drug products. At Ardena, Iñaki leads formulation and production activities, supporting drug product development from pre-formulation through clinical supply and commercial readiness. His expertise includes oral solid dosage forms, pharmaceutical process transfer, Quality by Design (QbD), experimental design (DoE), and solubility enhancement technologies, including spray drying. Iñaki brings extensive technical and operational experience across pharmaceutical development and manufacturing environments, supporting efficient and compliant drug product development programs.
