Pediatric application of ODTs
Although ODTs in general offer improved convenience and are frequently preferred over conventional solid oral-dosage forms,
ODTs may lead to significant improvements over current treatment options for specific patient groups, for instance, pediatric
patients. The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) described orodispersible dosage
forms as having "great promise for children" (4). The use of an ODT formulation of ondansetron has been found to be helpful
in the treatment of children as young as 6 months of age suffering from gastroenteritis and dehydration (5).
To enable the potential benefits of ODT formulations to be fully realized, the additional requirements of this group also
need to be considered, and the ease with which the different types of ODT can be adapted to meet these requirements will affect
their overall application and commercial potential. Clearly, size and disintegration time are particularly important. A fast
disintegration time will reduce any potential choking hazard and will also make it harder to spit out the dose. Similarly,
the taste and texture of pediatric formulations are critical to facilitate compliance in children, particularly for chronic
conditions where repeated administration may be an issue. Specific consideration needs to be given to the type and level of
flavors and sweeteners used in pediatric formulations, especially where artificial ingredients are used. The choice and level
of other excipients requires similar review for pediatric formulations, where there may be established limits for children
or where there is a lack of excipient safety data for this population.
As solid-unit doses, ODTs generally offer improved dose accuracy, storage, and stability advantages over liquid preparations.
However, for pediatric applications, ODTs also need to be able to accommodate a wider range of doses, particularly at the
lower end. ODT technologies that can offer low-dose accuracy will be of particular benefit to this group. In addition, clinical
studies in pediatrics are required to confirm acceptable safety and efficacy in the target patient group, but the initial
selection of an ODT for pediatric indications and compliance with the FDA ODT recommendations would help to eliminate the
risk of unsuccessful administration.
As discussed, the need for the ODT guidance was precipitated by the range of available ODT technologies and their differing
product characteristics. The formulation and process considerations of these different technologies and the product characteristics
relevant to their performance as an ODT are reviewed in the following section. Thin-film technology, while not falling under
the definition of an ODT, is designed to meet the same objective of oral delivery without administrating water or chewing,
and is also mentioned. The product attributes desirable for ODTs are summarized in Table I.
Table I: Target quality and performance attributes for orally disintegrating tablets (ODTs).
Current commercially available ODT technologies can be broadly categorized according to their method of manufacture as follows:
- Lyophilized tablets
- Compressed tablets
- Other (including molded tablets, spray-dried powders, and sugar floss).
Examples of each ODT technology platform are provided in Table II.
Table II: Orally disintegrating tablet technology platforms.