Pharmaceutical formulation

1. A film suitable for administration to an oral cavity comprising:

(i) an alginate salt of a monovalent cation or a mixture of alginate salts containing at least one alginate salt of a monovalent cation, wherein said alginate salt is a sodium alginate or a potassium alginate;

(ii) an active pharmaceutical ingredient (API) which is adrenaline or a pharmaceutically acceptable salt thereof;

(iii) an antioxidant selected from the group consisting of sodium metabisulfite, sodium bisulfite, and combinations thereof; and

(iv) at least one plasticizer which is selected from sorbitol, glycerol, or both sorbitol and glycerol,

further wherein the alginate salt of a monovalent cation (a) comprises from 25 to 35% by weight of β-D-mannuronate and from 65 to 75% by weight of α-L-guluronate, and (b) has a weight average molecular weight of from 30,000 g/mol to 90,000 g/mol,

wherein the film is stable for 83 days at room temperature.

2. The film according to claim 1 , wherein the API is (−)-adrenaline or a pharmaceutically acceptable salt thereof.

3. The film according to claim 1 , wherein the API is the tartrate salt of adrenaline.

4. The film according to claim 1 , wherein the alginate salt of a monovalent cation is a sodium alginate.

5. The film according to claim 1 , wherein the film comprises from 25% to 99% by weight of the alginate salt of a monovalent cation or the mixture of alginate salts containing at least one alginate salt of a monovalent cation, from 0% to 20% by weight of water, and from 0.001% to 75% by weight of the API.

6. The film according to claim 1 , wherein the film comprises from 29% to 93% by weight of the alginate salt of a monovalent cation or the mixture of alginate salts containing at least one alginate salt of a monovalent cation, from 5% to 15% by weight of water, and from 0.15% to 50% by weight of the API.

7. The film according to claim 1 , wherein the film comprises from 0.01 to 10% by weight of the antioxidant.

8. The film according to claim 1 , wherein the film comprises sodium metabisulfite or sodium bisulfite and at least one further antioxidant.

9. The film according to claim 1 , wherein the ratio of total antioxidants present in the film to total API present in the film, by weight, is from 0.01:1 to 10:1.

10. The film according to claim 8 , wherein the film comprises (i) ascorbic acid and (ii) sodium bisulfite or sodium metabisulfite.

11. The film according to claim 1 , wherein the film further comprises a basifying agent.

12. The film according to claim 1 , wherein the film comprises up to 40% by weight of sorbitol, and up to 40% by weight of glycerol.

13. A method of treating anaphylaxis, superficial bleeding, or cardiac arrest in a human patient, wherein said method comprises administration of at least one film according to claim 1 to said human patient.

14. The method of claim 13 , wherein the film is administered to the oral cavity of the human patient.

15. A method of manufacturing a film according to claim 1 , said method comprising:

(a) either:

(i) mixing the API in water, or in a solution comprising water and at least one antioxidant selected from the group consisting of sodium metabisulfite, sodium bisulfite, and combinations thereof;

(ii) mixing one or more excipients into the solution obtained; and

(iii) adding the alginate salt of monovalent cation to result in the formation of a cast;

or alternatively:

(iv) mixing one or more excipients in water;

(v) separately, dissolving the API in water, or an aqueous solution containing at least one antioxidant selected from the group consisting of sodium metabisulfite, sodium bisulfite, and combinations thereof;

(vi) mixing the solution obtained in (iv) with the alginate salt of monovalent cation; and

adding the solution obtained in (v) to the solution obtained in (vi) to result in the formation of a cast;

(b) leaving the cast to de-aerate;

(c) pouring the cast onto a surface and spreading the cast out to the desired thickness; and

(d) drying the cast layer until the residual water content of the film is from 0 to 20% by weight and a solid film is formed.

16. The method of claim 15 , wherein after the cast is poured onto a surface, it is first spread out to a thickness of about 2 mm by means of an applicator with a slit height of about 2 mm, and is then subsequently spread out to a thickness of about 1 mm by means of an applicator with a slit height of about 1 mm.

17. The film according to claim 8 , wherein the film comprises citric acid and sodium metabisulfite.

18. The film according to claim 1 , wherein the film comprises both sorbitol and glycerol.

19. The film according to claim 1 , wherein the film comprises sorbitol, glycerol, sodium metabisulfite and citric acid.

20. The film according to claim 6 , wherein the film comprises from 0.01% to 10% by weight of each antioxidant present and from 3% to 25% by weight of each plasticizer present.

21. The method of claim 13 , wherein the method is a method of treating anaphylaxis.

22. The film of claim 1 , wherein the ratio of total antioxidants present in the film to total API present in the film, by weight, is from 0.25:1 to 10:1.

23. The film of claim 1 , wherein the film comprises sodium metabisulfite or sodium bisulfite, and wherein said sodium metabisulfite or said sodium bisulfite is in a molar amount of from 0.001 to 1.0 per mole of the API present in the film.

24. The film according to claim 3 , wherein the API is the tartrate salt of (−)-adrenaline.

25. The film according to claim 9 , wherein the ratio of total antioxidants present in the film to total API present in the film, by weight, is from 0.5:1 to 10:1.

26. The film according to claim 11 , wherein the basifying agent is aqueous sodium hydroxide.