Process for loading a drug delivery device

#The present invention relates generally to methods of incorporating a composition onto a bioerodible, water-soluble pharmaceutical carrier device to efficiently manufacture a device that can optimally deliver the composition either systemically or locally.

#A number of mucoadhesive devices are available for the delivery of active agents locally or systemically through a mucus membrane or within a mucosally lined body cavity. Many of these devices are in the form of a film or patch that conveniently fit within a cavity, commonly the mouth, and adhere to a mucus membrane. They are commonly designed to be pressure sensitive, and they adhere immediately upon application to a membrane.

#The BEMA™ (Bioerodible Muco-Adhesive Film) Drug Delivery System is a bioerodible film for fast-acting local or systemic delivery of active agents. The BEMA™ technology provides a mucoadhesive and bioerodible disc for application to a mucosal surface and is used for transmucosal delivery of active agents over variable lengths of time, for example, delivery occurring for minutes or hours. The BEMA technology is disclosed in Tapolsky, et al. (U.S. Pat. No. 5,800,832) and Tapolsky, et al. (U.S. Pat. No. 6,159,498) the entire contents of which are hereby incorporated by reference.

#FIG. 1 provides the plasma concentrations of ondansetron after application of preloaded and post-loaded BEMA™-Ondansetron discs.

#FIG. 2 provides the plasma hydrocodone concentrations (mean±standard error) after application to the mucosal surfaces of dogs of preloaded BEMA™-Hydrocodone discs (7.2 mg/disc hydrocodone bitartrate, open circles) and post-loaded BEMA™-Hydrocodone discs (3 mg/disc formed by 3 discrete deposits of hydrocodone free base, closed circles).

#FIG. 3 provides plasma hydrocodone concentrations (mean±standard error) after application of post-loaded BEMA™-Hydrocodone discs with 1 discrete post-load deposit (filled triangles), 3 discrete post-load deposits (filled circles), or 5 discrete post-load deposits (open circles).

#The invention provides a method for loading a composition into a pre-assembled water-soluble, bioerodible carrier device that can adhere to mucosal surfaces. The method generally involves applying the desired amount of the composition onto one or two surfaces of the water-soluble carrier device. For pharmaceutical compositions, a therapeutically effective amount of an active ingredient(s) or pharmaceutical(s) can be deposited onto one or more surfaces of the water-soluble carrier device. The composition can be applied to the chosen surface(s) in the form of a liquid or solid. After applying the composition to form a loaded device, the bioadhesive layer of the bioerodible carrier device can be placed in contact with a mucosal surface of a mammal for delivery of the active ingredient(s) or pharmaceutical(s) within the composition.

#The composition to be incorporated into the water-soluble, bioerodible pharmaceutical device can be applied as a liquid in the form of a solution, suspension or melted composition, or as a solid in the form of a powder, film or tablet. The composition is prepared with the active ingredient(s) or pharmaceutical(s) and any pharmaceutically acceptable excipients selected by one of skill in the art. Any convenient excipient can be included into the solution. Examples include, but are not limited to, viscosity-building agents (both polymeric and nonpolymeric), hydrophilicity agents (both polymeric and nonpolymeric), coloring agents and other excipients described herein. Examples of a viscosity-building agents include hydroxypropylcellulose and hydroxyethylcellulose. An example of a hydrophilicity agent is polyethylene glycol.

#The solvent used for the solution or suspension can vary and depends upon the active ingredient(s) or pharmaceutical(s) employed as well as the other components of the composition. In general, one of skill in the art can select a good solvent for the composition to be incorporated into the water-soluble, bioerodible pharmaceutical device. Preferred solvents include organic-based solvents that have a high vapor pressure or a low normal boiling point and that have regulatory acceptance as a pharmaceutical solvent suitable for oral administration. Examples of solvents useful for preparing and dispensing a solution or suspension of active ingredient(s) or pharmaceutical(s) include, for example, acetic acid, acetone, anisole, 1-butanol, 2-butanol, butyl acetate, tert-butylmethyl ether, cumene, dimethyl sulfoxide, ethanol, ethyl acetate, ethyl ether, methanol, ethyl formate, formic acid, heptane, isobutyl acetate, isopropyl acetate, methyl acetate, 3-methyl-1-butanol, methylethyl ketone, methylisobutyl ketone, 2-methyl-1-propanol, pentane, 1-pentanol, 1-propanol, 2-propanol, propyl acetate, and tetrahydrofuran. Preferred solvents that may be used include methanol, ethanol or isopropanol.