FILM FORMULATIONS CONTAINING DEXMEDETOMIDINE AND METHODS OF PRODUCING THEM
Disclosed herein is a self-supporting, dissolvable, film containing dexmedetomidine or a pharmaceutically acceptable salt thereof. The film is administered orally to treat various conditions, particularly agitation, by transmucosal delivery of the active agent.
1 . An oromucosal formulation comprising:
dexmedetomidine or a pharmaceutically acceptable salt thereof; and
at least one water-soluble polymer;
wherein the at least one water-soluble polymer is selected from the group consisting of hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, carboxy methylcellulose, methylcellulose, polyethylene oxide (PEO), and mixtures thereof; and
wherein the oromucosal formulation provides at least 45.6% bioavailability when administered to an oral mucosa of an animal subject that is a male New Zealand White Oryctolagus cuniculus with an initial body weight between 2.9 kg and 3.9 kg.
2 . The oromucosal formulation of claim 1 , wherein the oromucosal formulation provides at least 52.2% bioavailability when administered to the animal subject.
3 . The oromucosal formulation of claim 1 , wherein the oromucosal formulation provides at least 63.4% bioavailability when administered to the animal subject.
4 . The oromucosal formulation of claim 1 , wherein the oromucosal formulation provides at least 70.5% bioavailability when administered to the animal subject.
5 . The oromucosal formulation of claim 1 , wherein the oromucosal formulation provides a C max /dose ratio no lower than 0.119 [(ng/mL)/(μg/kg)] in more than 50% of the animal subjects.
6 . The oromucosal formulation of claim 1 , wherein the oromucosal formulation provides a C max /dose ratio no lower than 0.119 [(ng/mL)/(μg/kg)] in at least 75% of the animal subjects.
7 . The oromucosal formulation of claim 1 , wherein the oromucosal formulation provides a C max /dose ratio no lower than 0.119 [(ng/mL)/(μg/kg)].
8 . A method of treating agitation in a human patient comprising administering to the human patient an oromucosal formulation;
wherein the oromucosal formulation comprises an effective amount of dexmedetomidine or a pharmaceutically acceptable salt thereof and at least one water-soluble polymer;
wherein the at least one water-soluble polymer is selected from the group consisting of hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, carboxy methylcellulose, methylcellulose, polyethylene oxide (PEO), and mixtures thereof; and
wherein the oromucosal formulation provides at least 45.6% bioavailability when administered to an oral mucosa of an animal subject with a body-weight adjusted dose, wherein the animal subject is a male New Zealand White Oryctolagus cuniculus with an initial body weight between 2.9 kg and 3.9 kg.
9 . The method of claim 8 , wherein the oromucosal formulation provides at least 52.2% bioavailability when administered to the animal subject.
10 . The method of claim 8 , wherein the oromucosal formulation provides at least 63.4% bioavailability when administered to the animal subject.
11 . The method of claim 8 , wherein the oromucosal formulation provides at least 70.5% bioavailability when administered to the animal subject.
12 . The method of claim 8 , wherein the oromucosal formulation provides a C max /dose ratio no lower than 0.119 [(ng/mL)/(μg/kg)] in more than 50% of the animal subjects.
13 . The method of claim 8 , wherein the oromucosal formulation provides a C max /dose ratio no lower than 0.119 [(ng/mL)/(μg/kg)] in at least 75% of the animal subjects.
14 . The method of claim 8 , wherein the oromucosal formulation provides a C max /dose ratio no lower than 0.119 [(ng/mL)/(μg/kg)].