PHARMACEUTICAL FORMULATION
A film comprising an alginate salt of a monovalent cation or a mixture of alginate salts containing at least one alginate salt of a monovalent cation, and a triptan or a pharmaceutically acceptable salt thereof, are described. Methods for manufacturing such a film, and the use of such a film in the treatment of disease in a human patient, in particular migraine with or without aura, cluster headache, or trigeminal neuralgia, are also described.
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; and
(ii) a triptan or a pharmaceutically acceptable salt thereof.
2 . The film according to claim 1 , wherein the triptan or a pharmaceutically acceptable salt thereof is sumatriptan, zolmitriptan, naratriptan, rizatriptan, almotriptan, eletriptan, frovatriptan or donatriptan, or a pharmaceutically acceptable salt thereof.
3 . The film according to claim 2 , wherein the triptan or a pharmaceutically acceptable salt thereof is sumatriptan or a pharmaceutically acceptable salt thereof.
4 . The film according to claim 1 , wherein the alginate salt of a monovalent cation is selected from a sodium alginate, a potassium alginate and an ammonium alginate.
5 . The film according to claim 1 , wherein the alginate salt of a monovalent cation comprises from 25 to 35% by weight of β-D-mannuronate and/or from 65 to 75% by weight of α-L-guluronate.
6 . The film according to claim 1 , wherein the alginate salt of a monovalent cation has a mean molecular weight of from 30,000 g/mol to 90,000 g/mol.
7 . The film according to claim 4 , wherein the alginate salt of a monovalent cation is a sodium alginate.
8 . 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.
9 . The film according to claim 1 , wherein the film comprises from 30% to 86% 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 4% to 40% by weight of the API.
10 . The film according to claim 1 , wherein the film further comprises:
a buffering component which is sodium dihydrogen phosphate;
at least one plasticizer which is selected from sorbitol, glycerol, or a combination thereof; and
an acidifying agent which is aqueous phosphoric acid.
11 . The film according to claim 8 , wherein the film further comprises from 0.1% to 10% by weight of sodium hydrogen phosphate, from 0% to 40% by weight of sorbitol, and from 0% to 40% by weight of glycerol.
12 - 15 . (canceled)
16 . A method of treating migraine with or without aura, cluster headache, or trigeminal neuralgia in a human patient, wherein said method comprises administration of at least one film according to claim 1 to said human patient.
17 . (canceled)
18 . The method according to claim 16 , wherein the film is administered to the oral cavity of the human patient.
19 . A method of manufacturing a film according to claim 1 , said method comprising:
(a) mixing the triptan or a pharmaceutically acceptable salt thereof and, optionally, at least one buffering component in water;
(b) adjusting the pH of the solution to the desired level by addition of an appropriate acid or base, typically a diluted aqueous acid or alkali;
(c) optionally, adding further water and/or one or more plasticizers under further mixing;
(d) adding the alginate salt of monovalent cation under suitable conditions to result in the formation of a viscous cast;
(e) pouring the cast onto a surface and spreading the cast out to the desired thickness;
(f) drying the cast layer until the residual water content of the film is from 5 to 15% by weight and a solid film is formed; and
(g) optionally, cutting the solid film into pieces of the desired size, further optionally placing these pieces into pouches, sealing the pouches and further optionally, labelling them.
20 . The method of claim 19 , wherein after the viscous 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.
21 . The method according to claim 16 , wherein the human patient suffers from nausea and/or dysphagia.
22 . The method according to claim 16 , wherein the human patient is additionally receiving treatment for one or more types of cancer.
23 . The film according to claim 10 , wherein the at least one plasticizer is both sorbitol and glycerol.
24 . The method according to claim 19 , wherein in (b), the pH of the solution is adjusted to from 3.25 to 12.0.
25 . The method according to claim 19 , wherein in (f), the cast layer is dried at a temperature of from 45 to 70° C.