SUBLINGUAL AND BUCCAL FILM COMPOSITIONS
The present invention relates to products and methods for treatment of various symptoms in a patient, including treatment of pain suffered by a patient. The invention more particularly relates to self-supporting dosage forms which provide an active agent while providing sufficient buccal adhesion of the dosage form. Further, the present invention provides a dosage form which is useful in reducing the likelihood of diversion abuse of the active agent.
1 . A self-supporting film dosage composition comprising:
a. a polymeric carrier matrix;
b. a therapeutically effective amount of an agonist or a pharmaceutically acceptable salt thereof;
c. a therapeutically effective amount of an antagonist or a pharmaceutically acceptable salt thereof; and
d. a chelator or antioxidant;
wherein the ratio of said antagonist to said chelator or antioxidant is from about 40:1 to about 1:10 by weight.
2 . The composition of claim 1 , wherein said ratio of said antagonist to said chelator or antioxidant is from about 4:1 to about 1:10 by weight.
3 . The composition of claim 1 , wherein said ratio of said antagonist to said chelator or antioxidant is from about 5:1 to about 1:2 by weight.
4 . The composition of claim 1 , wherein said ratio of said antagonist to said chelator or antioxidant is from about 1:2 to about 2:1 by weight.
5 . The composition of claim 1 , wherein said chelator or antioxidant is selected from the group consisting of ethylenediaminetetraacetic acid (EDTA) and salts thereof, proteins, polysaccharides, polynucleic acids, glutamic acid, histidine, organic diacids, polypeptides, phytochelatin, hemoglobin, chlorophyll, humic acid, phosphonates, transferrin, desferrioxamine, dibutylhydroxytoluene (BHT), dibutylated hydroxyanisole (BHA), propyl gallate, sodium sulfate, citric acid, sodium metabisulfite, ascorbic acid, tocopherol, tocopherol ester derivatives, 2-mercaptob enzimidazoleand, and combinations thereof.
6 . The composition of claim 1 , wherein said chelator or antioxidant is ethylenediaminetetraacetic acid disodium salt.
7 . The composition of claim 1 , wherein said antagonist is naloxone or a pharmaceutically acceptable salt thereof.
8 . The composition of claim 1 , wherein said agonist is buprenorphine or a pharmaceutically acceptable salt thereof.
9 . The composition of claim 1 , wherein said antagonist is naloxone or a pharmaceutically acceptable salt thereof and said agonist is buprenorphine or a pharmaceutically acceptable salt thereof.
10 . The composition of claim 1 , wherein said composition comprises a first region and a second region, said first region comprising said agonist and said second region comprising said antagonist.
11 . A self-supporting film dosage composition comprising:
a. a polymeric carrier matrix;
b. a therapeutically effective amount of buprenorphine or a pharmaceutically acceptable salt thereof;
c. a therapeutically effective amount of naloxone or a pharmaceutically acceptable salt thereof; and
d. a chelator or antioxidant;
wherein the ratio of said naloxone or a pharmaceutically acceptable salt thereof to said chelator or antioxidant is from about 40:1 to about 1:10 by weight.
12 . The composition of claim 11 , wherein said ratio of said naloxone or a pharmaceutically acceptable salt thereof to said chelator or antioxidant is from about 4:1 to about 1:10 by weight.
13 . The composition of claim 11 , wherein said ratio of said naloxone or a pharmaceutically acceptable salt thereof to said chelator or antioxidant is from about 5:1 to about 1:2 by weight.
14 . The composition of claim 11 , wherein said ratio of said naloxone or a pharmaceutically acceptable salt thereof to said chelator or antioxidant is from about 1:2 to about 2:1 by weight.
15 . The composition of claim 11 , wherein said chelator or antioxidant is selected from the group consisting of ethylenediaminetetraacetic acid (EDTA) and salts thereof, proteins, polysaccharides, polynucleic acids, glutamic acid, histidine, organic diacids, polypeptides, phytochelatin, hemoglobin, chlorophyll, humic acid, phosphonates, transferrin, desferrioxamine, dibutylhydroxytoluene (BHT), dibutylated hydroxyanisole (BHA), propyl gallate, sodium sulfate, citric acid, sodium metabisulfite, ascorbic acid, tocopherol, tocopherol ester derivatives, 2-mercaptobenzimidazole and combinations thereof.
16 . The composition of claim 11 , wherein said chelator or antioxidant is ethylenediaminetetraacetic acid disodium salt.
17 . The composition of claim 11 , further comprising a buffer in an amount sufficient to maximize the absorption of the buprenorphine or a pharmaceutically acceptable salt thereof.
18 . The composition of claim 11 , further comprising a buffering system comprising a buffer capacity sufficient to inhibit the absorption of said naloxone or a pharmaceutically acceptable salt thereof during the time which said composition is in the oral cavity of a user.
19 . The composition of claim 11 , wherein said composition comprises a first region and a second region, said first region comprising said buprenorphine or a pharmaceutically acceptable salt thereof and said second region comprising said naloxone or a pharmaceutically acceptable salt thereof.
20 . The composition of claim 11 , wherein said buprenorphine or a pharmaceutically acceptable salt thereof has a local pH of about 3 to about 9.