OraVescent and OTS Transmucosal Delivery Systems

Oral Transmucosal Drug Delivery

Oral transmucosal dosage forms such as buccal and sublingual tablets or lozenges can offer distinct advantages to conventional, orally swallowed dosage forms. Oral transmucosal forms are intended to deliver drugs which are absorbed directly through the oral mucosa rather than in the gastrointestinal tract. Delivery of drugs in this manner reduces exposure of the drug to the acidic and enzymatic conditions of the gastrointestinal tract, the first pass effect of the liver and the time delay of systemic delivery. Transmucosal drug delivery can result in a greater rate and extent of drug uptake into the systemic circulation, which may also result in faster onset of action and reduce the dose of drug required to produce a therapeutic effect.

in pH causes the ionized drug to convert predominantly to the un-ionized form, which can be more permeable to biological tissues and can result in more rapid absorption. OraVescent tablets are manufactured by a conventional direct compression manufacturing process. CIMA LABS offers the PakSolv packaging service and technology for use in the manufacture of OraVescent products. This packaging system forms aluminum foil blisters, gently places the tablets into the blisters, and places a seal on the blister which protects the tablets from breakage, light, and moisture. The FENTORA product (fentanyl buccal tablet, C-II) is developed with the OraVescent drug delivery system. For important information for healthcare professionals and patients, and for Prescribing Information including the boxed warning on FENTORA, please visit www.fentora.com.

OraVescent Tablet Technology

The OraVescent tablet, an oral transmucosal delivery system, is intended to be placed in the oral cavity either sublingually or between the buccal and gingival tissues, where it is allowed to disintegrate passively over several minutes. In addition to the benefits of oral transmucosal delivery, the OraVescent technology has been shown to provide enhanced systemic absorption of some drugs across the mucosal tissue due to its unique mechanism of action. The enhanced performance of the OraVescent tablet is thought to be related to dynamic, localized, transient pH changes that occur over the course of tablet disintegration and dissolution. As the tablet disintegrates in the oral cavity, a chemical reaction occurs between acidic and basic components in the tablet after contact with water in the saliva. This results in the liberation of carbon dioxide and produces a modest decrease in the pH of the tablet microenvironment. For weakly basic drugs, a lower pH (below its pKa) favors the ionized form of the drug, accelerating its dissolution. As a pH-modifying substance present in the tablet (e.g. sodium carbonate) dissolves, the pH increases. This increase

OTS Drug Delivery Technology

The OTS technology is another unique, oral transmucosal drug delivery system offered by CIMA LABS. The OTS system utilizes a lozenge on a stick technology where the dosage unit is administered by rotating and dissolving it against the oral mucosal tissue. This delivery system is unique in that it allows the patient to easily control the administration of the drug in the oral cavity. The presence of a handle on the dosage form provides a convenient, simple mechanism for the patient to deliver drugs to the oral cavity for either transmucosal or swallowed gastrointestinal absorption, depending on the drug application. This technology has also been commercialized with fentanyl citrate as the active drug under the brand name ACTIQ (oral transmucosal fentanyl citrate, C-II). For important information for healthcare professionals and patients, and for prescribing information including the boxed warning on ACTIQ, please visit www.actiq.com.

OraVescent and OTS Transmucosal Delivery Systems (continued)

The OTS product is also manufactured by a direct compression process and is packaged in a convenient unit dose blister package. CIMA LABS is a leader in oral transmucosal drug delivery. With two unique technologies that have been commercialized, CIMA LABS has the know-how to develop and manufacture a successful product. If you are interested in learning about our oral transmucosal drug delivery technologies for your molecule, please contact Richard Welter, Ph.D., V.P. of Business Development at 763-488-4790 or John C. Nagel, MBA, Senior Director of Business Development at 763-488-4975.
2008 CIMA LABS INC. All rights reserved. CIMA LABS(SM) is a servicemark of Cephalon, Inc. OraVescent , Fentora and PakSolv are trademarks of CIMA LABS INC. Actuq and OTS are trademarks of Anesta Corp.