"Compressed tablet systems are based on conventional tableting technology and vary in their degree of hardness and friability,"
explains Rosie McLaughlin, director of product development at Catalent. "This variability results in varying disintegration
characteristics depending on the exact materials and process used, but typically disintegration times are higher than for
lyophilized ODT formulations." Also, friable products may require specific packaging considerations. Loosely compressed ODT
tablets generally rely on water-soluble excipients and/or super disintegrants to achieve rapid disintegration (30–60 s) (5).
In response to growing interest for ODTs, several companies are advancing production capabilities and technologies.
Catalent Pharma Solutions, for example, recently added "Zydis" ODT commercial manufacturing capability at its facility in
Somerset, New Jersey. A commercial Zydis line was installed into a space in existing buildings, which had originally been
designed to accommodate future expansion. The line will be operational in 2007, and commercial production from the site is
anticipated in 2009 pending associated regulatory filings.
"The Zydis process involves the preparation of an aqueous solution or suspension, from which individual units are dosed and
freeze-dried," explains McLaughlin."The liquid-dosing process ensures good dose uniformity and facilitates containment of
the active ingredient. The freezing process then results in a network of ice crystals that are sublimed during lyophilization
to produce a highly porous structure, which facilitates the rapid dispersion characteristics of the product," she says.
McLaughlin says the key advantage of the lyophilization technology used in the Zydis manufacture is the highly porous structure
and consequent extremely rapid dispersion achieved (typically less than 5 s). The formulations are generally simple, typically
incorporating two structure-forming agents with the API, in a ratio optimized for each product, plus any additives specifically
required such as flavors, sweeteners, or pH modifying agents.
Select companies with orally disintegrating tablets technology.
In addition to conventional small molecules, the lyophilization process has also been shown to be suitable for the formulation
of peptide and protein drug molecules. "Protein and peptide molecules are physically and chemically sensitive, and lyophilization
processes are typically used in their manufacture owing to the relatively low stresses applied during processing (e.g. low
temperatures)," says McLaughlin.
Several peptide and protein-based drugs use the Zydis ODT technology, including "Grazax, " a grass-pollen allergy vaccine
by ALK-Abelló(Hoersholm, Denmark).
Catalent is providing commercial production of Grazax at its facility in Swindon, United Kingdom. In August 2007, Catalent
reported that ALK-Abelló will fund a new production line for current and future tablet-based allergy products at Catalent's
Swindon facility. Commercial production on the new line is expected to begin in 2010.
Eurand (Vandalia, Ohio) has partnered with GlaxoSmithKline (GSK, London) to develop an ODT formulation of an undisclosed compound. Last October, the companies signed a formulation
development pact under which GSK is using Eurand's "AdvaTab" oral disintegration tablet technology and "Microcaps" taste-masking
"The new formulation for GlaxoSmithKline dissolves in the mouth in approximately 30 seconds without water and without leaving
a bitter or sour taste," said Eurand CEO Gearóid Faherty in a June 2007 release. GSK has started a registration bioequivalence
study for the new formulation and will make a milestone payment of $1 million to Eurand in recognition of the initiation
of this biostudy. GSK intends to file for marketing authorization in the United States by the end of 2007.