Table III.
Aspects Supporting or Limiting the Use of Orally Disintegrating Films and Mini-Tablets in Pediatrics
| Challenge | Regulatory claims (EMA guideline) |
Orally disintegrating film and mini-tablet preparations | Scientific reference/supported by | |
|---|---|---|---|---|
| Advantages | Limitations | |||
| Size of dosage form | Children may not be able or willing to swallow a medicinal product/infants are simply unable to swallow conventionallysized tablets | Orodispersion Jelly behavior of polymer film facilitates swallowing |
Non dispersion due to low amounts of saliva | 2-mm mini-tablets (0.5–6 years) (21,22) 3-mm mini-tablets (2–6 years), derived recommendation: ≥4 years (29) 4-mm tablets used in food supplements (30) Facilitation of swallowing by using a cup system (31) or instant gelation of film layer (32) |
| Taste of the active substance | Overcoming taste issues: e.g., improved solubility (use of salt or different salt instead of base) e.g., less soluble form, e.g., base instead of salt |
Fast disintegration, swallowing with saliva, minimal mouth coating compared to liquids Coated or insoluble drug particles can be swallowed after disintegration of the dosage form |
Suitability of taste-masking agents (safety aspects, acceptable daily intake levels) Limited drug load/ Decreased drug load depending on taste-masking strategy |
Less soluble APIs: taste of suspension accepted compared to placebo (33) Less bitterness of less soluble base (34) Free acid is more palatable than salt (35,36) |
| Oral administration | Solid single-unit dosage form: stable and easy dosing approach Dosing flexibility: greater for oral powders, granules, and liquids than for oral solid single-unit dosage forms Liquids: avoiding multiple step procedures (risk of dosing errors) |
See EMA claim Dosing flexibility of mini-tablets No need to split large tablets Dose by film size |
Multiple dosing might be necessary | Mini-tablets (17,18) ODFs prepared on a small scale for individual dosing (17,18,37) Content variation in split tablets (38) |
| Dosing frequency | Preferred: maximum of twice daily dosing Special attention when medicines used more than twice daily (suitability of administration when no trained caregiver is around, e.g., in day care or school) |
Ease of administration/administration on demand No special training needed Flexibility of dosage form enables tailoring the medication regimen to the child’s daily routine |
Multiple dosing might be necessary due to the limited drug load per single unit | Adherence to multiple dose regimen (39,40) |
| Measuring device Risk of dosing errors |
Ensure the ease and accuracy of the administration Oral liquids: oral syringe should be more readily considered in the youngest age groups than a spoon or a cup |
No liquid dosing device such as cups or syringe needed Lower risk of dose dumping |
No multiple step procedure for liquids compared to the intake of multiple films/tablets to administer the required dose | Suitability of the graduation of delivery devices (14,41,42) Accuracy of dosing devices (14) Parents’ accuracy in using dosing devices for liquids (12) |
| Excipients | Key element of the development Special safety considerations for children |
Film-forming polymer material is widely used e.g., for other pharmaceutical coating processes Known tableting excipients |
Choice of solvent in film preparations Suitability of taste-masking agents |
Safety and toxicity considerations on taste-masking agents and coating materials (43) Influence on bioavailability (44) Careful use of solvents and sweeteners (45) Issues relating to the risk assessment of excipients in neonates (46) |