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.

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 companies.

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 Banbury.