CIMA Labs, a subsidiary of Cephalon (Frazer, PA) is positioned in ODT technology through its "OraSolv" and "DuraSolv" platforms that are based on compressed-tablet
technology. OraSolv is an ODT that combines taste-masked active drug ingredients with a low effervescence system. DuraSolv
is an ODT that combines taste-masked active drug ingredients with or without a low effervescence system (1). Cima's parent
company, Cephalon's "Lyoc" technology is an ODT platform that uses freeze-drying methods (see sidebar, "Companies with orally
disintegrating tablet technology").
Challenges in ODT
Although ODTs offer benefits, there are factors to consider. "The challenges of developing ODT products are similar to those
for conventional solid oral dosage forms in terms of the need to establish compatibility of the active drug substance with
the excipients and process," explains McLaughlin. "In addition, the intended oral dispersion of the units means that the specific
taste and mouthfeel characteristics of the drug substance are particularly relevant." Sweeteners and flavors are typically
included to achieve a palatable formulation, but additional taste-masking strategies may also be required such as ion-exchange
resins and active pharmaceutical ingredient (API) encapsulation.
"Another challenge is that ODTs are potentially less robust than conventional solid-oral dosage forms, given their formulation
to achieve rapid disintegration (e.g.,increased friability and greater moisture sensitivity), so packaging requirements need
to be considered early in the development process," says McLaughlin.
In the case of the Zydis ODT technology, the blister pack is an integral part of the product, forming the molds for the individual
unit doses. Following freeze drying, the blister packs are sealed, and the units are not removed until the point of administration,
thereby providing physical protection throughout the manufacturing and distribution process. The use of all aluminum blister
packs also provides effective moisture protection throughout the product shelf-life, typically two to five years.
As for any other dose form, the bioavailability of ODT products is governed by the physicochemical characteristics of the
API and formulation optimization. "The extent of pregastric formulation is largely dependent on the physicochemical characteristics
of the drug, but the formulation may aim to maximize the potential to optimize bioavailability, or minimize the effect to
ensure bioequivalence with a perorally absorbed dosage form," says McLaughlin. Typical formulation variables considered are
solubility and particle size of the API, formulation pH, and formulation constituents, in particular taste- masking agents.
Widening the scope of ODT
Industry observers point to broadening uses of ODT technology. These include the incorporation of macromolecules using ODT
into vaccines. "The success for other peptide and protein products will depend on bioavailability requirements and the application
of methods to overcome oral absorption barriers," says Catalent's Banbury. Other areas include: the incorporation of encapsulated
APIs to achieve modified-release profiles within the convenience of an ODT; and the further development of super disintegrants
for incorporation into conventional, compressed tablets, potentially widening the opportunity for ODT development to nonspecialist
Another emerging area is the wider application of oral thin-strip technologies. "The use of thin-film strips is of growing
interest in the pharmaceutical sector following the success of Listerine PocketPaks in the United States," observes Banbury.
Thin-film strip technology uses a range of water-soluble polymers and is reported to be able to incorporate water-soluble,
insoluble, or taste-masked ingredients. The film is manufactured as a continuous sheet and then cut into individual doses
prior to packing. The major limitations to this technology are the relatively low doses that can be accommodated (approximately
30 mg) and its moisture sensitivity requiring specific unit-dose packaging to protect the product and ensure shelf life, explains