Dosage form for insertion into the mouth
Oral dosage forms as a biodegradable, water soluble film for delivering pharmaceutically active agents, particularly anti-migraine agents to patients through insertion into the mouth of patient and methods for administering pharmaceutically active agents to patients by insertion into the mouth to provide selective uptake of said agents through the mucosa and thus avoiding the gastrointestinal tract.
1. A pharmaceutical composition for application to the oral mucosa comprising:
a water soluble matrix comprising an effective amount of a pharmaceutically active agent and an absorption enhancer having an HLB of about 8 to about 16, wherein the matrix is a film, the absorption enhancer is one or more sucrose fatty acid esters and the pharmaceutically active agent is a triptan or its pharmaceutically acceptable salts.
2. The pharmaceutical composition of claim 1 further comprising a nonionic surfactant wherein the combined nonionic surfactant and sucrose fatty acid ester have a combined HLB of about 8 to about 17.
3. The pharmaceutical composition of claim 2 wherein the nonionic surfactant is at least one or more of polysorbate and sorbitan fatty acid ester.
4. The pharmaceutical composition of claim 2 further comprising a secondary absorption enhancer selected from the group consisting of glycerol, ginger oil, cineole and terpenes.
5. The pharmaceutical composition of claim 3 wherein the polysorbate is selected from the group consisting of polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (20) sorbitan monopalmitate, polyoxyethylene (20) sorbitan and Polyoxyethylene (20) sorbitan monooleate.
6. The pharmaceutical composition of claim 3 wherein the sorbitan fatty acid ester is selected from the group consisting of sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan tristearate and sorbitan monooleate.
7. The pharmaceutical composition of claim 1 further comprising a film forming agent selected from pullulan or a polymeric mixture of polyvinyl pyrrolidone and a polymeric alginate.
8. The pharmaceutical composition of claim 1 wherein the triptan is selected from the group consisting of eletriptan, frovatriptan, sumatriptan, zolmitriptan, naratriptan, rizatriptan, almotriptan and their pharmaceutically acceptable salts.
9. The pharmaceutical composition of claim 1 wherein the active agent is selected from the group consisting of Smoking cessation drugs, Narcotic analgesics, Anesthetic, Antitussives, Normarcotic analgesics such as the nonsteroidal anti-inflammatory agents (NSAIDS), Erectile dysfunction, Female sexual dysfunction, Antihistamines, Colds and Allergy, Cough, Respiratory Disorders, Sore Throat, Respiratory Disorders, Heartburn and Dyspepsia, Antiemetics, Sleep aids, Diarrhea, Oral Hygiene, Antagonists of CGRP receptors, Migrane treatment, Drugs for hormone replacement, Alzheimer's disease, Caffeine and Caffeine salt compounds.
10. The pharmaceutical composition of claim 8 wherein the triptan is rizatriptan or its pharmaceutically acceptable salts.
11. The pharmaceutical composition of claim 1 wherein the pharmaceutical composition further comprises a non-steroidal anti-inflammatory agent.
12. The pharmaceutical composition of claim 8 wherein the triptan is zolmitriptan or its pharmaceutically acceptable salts.
13. The pharmaceutical composition of claim 8 wherein the triptan is sumatriptan or its pharmaceutically acceptable salts.
14. The pharmaceutical composition of claim 1 wherein the pharmaceutical composition dissolves in the oral cavity in about 0.25 minutes to about 15 minutes.
15. The pharmaceutical composition of claim 7 wherein the film forming agent is pullulan.
16. The pharmaceutical composition of claim 1 wherein the triptan is present in an amount of from about 1 mg to about 50 mg as the base.
17. The pharmaceutical composition of claim 7 wherein the ratio of polyvinyl pyrrolidone to polymeric alginate in the polymeric mixture is from about 5:1 to about 1:3.
18. The pharmaceutical composition of claim 1 wherein the sucrose fatty acid esters are sucrose fatty acid esters having a monomer content of from about 20 percent to about 80 percent.
19. The pharmaceutical composition of claim 1 wherein the sucrose fatty acid esters are selected from the group consisting of sucrose stearate, sucrose palmitate, sucrose laurate, sucrose behenate, sucrose oleate and sucrose erucate.
20. The pharmaceutical composition of claim 7 wherein the polymeric mixture contains, from about 5% to about 95% by weight of polyvinyl pyrrolidone and from about 5% to about 95% by weight of an polymeric alginate, both of said weights being based on the weight of said polymeric mixture.
21. The pharmaceutical composition of claim 1 wherein the matrix is a tablet.
22. The pharmaceutical composition of claim 1 wherein the matrix is a liquid.
23. The pharmaceutical composition of claim 1 further comprising a polymeric mixture of polyvinyl pyrrolidone and a polymeric alginate.
24. The pharmaceutical composition of claim 1 wherein the film when placed in the oral cavity will dissolve in about 0.25 minutes to about 15 minutes.
25. The pharmaceutical composition of claim 21 wherein the tablet when placed in the oral cavity will dissolve in about 0.25 minutes to about 15 minutes.
26. The pharmaceutical composition of claim 1 wherein the film has a thickness of about 0.01 mm to about 5 mm.
27. The pharmaceutical composition of claim 1 wherein said film has a surface area of from 0.25 cm 2 to 20 cm 2 and a weight of about 1 mg to about 200 mg.
28. The pharmaceutical composition of claim 1 wherein said film has a surface area of from 1 cm 2 to 10 cm 2 and a weight of about 10 mg to about 200 mg.
29. The pharmaceutical composition of claim 1 wherein said film contains one or more absorption enhancers in an amount of from about 0.1% by weight to about 20% by weight of the film.
30. The pharmaceutical composition of claim 1 wherein said film contains one or more absorption enhancers in an amount of from about 0.1% by weight to about 15% by weight of the film.
31. The pharmaceutical composition of claim 1 wherein said film contains a absorption enhancer in an amount of from about 1% by weight to about 10% by weight of the film.
32. The pharmaceutical composition of claim 21 wherein said tablet contains a absorption enhancer in an amount of from about 0.1% by weight to about 20% by weight of the tablet.
33. The pharmaceutical composition of claim 21 wherein said tablet contains a absorption enhancer in an amount of from about 1% by weight to about 15% by weight of the tablet.
34. The pharmaceutical composition of claim 22 wherein said liquid contains a absorption enhancer in an amount of from about 0.1% by weight to about 10% by weight of the liquid.
35. The pharmaceutical composition of claim 3 wherein the polymeric mixture contains from about 5% to about 95% by weight of polyvinyl pyrrolidone and from about 5% to about 95% by weight of an polymeric alginate, both of said weights being based on the weight of said polymeric mixture.
36. The pharmaceutical composition of claim 1 wherein said matrix contains an absorption enhancer or a combination of absorption enhancers in a total amount of from about 0.1% by weight to about 20% by weight by weight of the matrix.
37. The pharmaceutical composition of claim 1 wherein said sucrose fatty acid ester is a C 12 to C 20 saturated fatty acid ester of sucrose.
38. The pharmaceutical composition of claim 1 wherein said sucrose fatty acid ester is a sucrose stearate.
39. The pharmaceutical composition of claim 10 wherein the rizatriptan is present in an amount of about 2.5 to about 15 mg as the base.
40. The pharmaceutical composition of claim 12 wherein the zolmitriptan is present in an amount of about 1 to about 7.5 mg as the base.
41. The pharmaceutical composition of claim 13 wherein the sumatriptan is present in an amount of about 3 to about 100 mg as the base.
42. The pharmaceutical composition of claim 25 , wherein the nonionic surfactant is at least one or more of polysorbate and sorbitan fatty acid ester.