Dosage form for insertion into the mouth
Oral dosage forms as a biodegradable, water soluble film for delivering pharmaceutically active 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 an agent for the treatment of pain in a patient and is present in an amount which is effective for treating said pain, wherein the agent for the treatment of pain is selected from the group consisting of fentanyl, hydromorphone, morphine, sufentanyl, methadone, buprenorphine, Acetaminophen, Ibuprofen, ketoprofen, indomethacin, aspirin (low dose for cardiovascular), naproxen sodium, ketorolac, diclofenac, meloxicam, and piroxicam.
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 7 wherein the film forming agent is pullulan.
9. 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.
10. 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.
11. The pharmaceutical composition of claim 1 wherein said sucrose fatty acid ester is a C12 to C20 saturated fatty acid ester of sucrose.
12. 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.
13. The pharmaceutical composition of claim 1 wherein said sucrose fatty acid ester is a sucrose stearate.
14. 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.
15. 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 or a surface area of from 1 cm 2 to 10 cm 2 about 200 mg and a weight of about 10 mg to 200 mg.
16. 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.
17. The pharmaceutical composition of claim 1 wherein the pharmaceutical composition dissolves in the oral cavity in about 0.25 minutes to about 15 minutes.
18. 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.
19. The pharmaceutical composition of claim 1 wherein the film has a thickness of about 0.01 mm to about 5 mm.
20. A method of drug delivery wherein at least a fraction of 1% to 80% or greater of the drug (F1) is delivered to and absorbed by the oral mucosa and absorbed systemically and a second fraction of greater than 1% to 80% is delivered to and absorbed along the continuous length of the esophagus and gastrointestinal tract wherein the first fraction (F1) results in a rapid onset of action and improved bioavailability and wherein the second fraction (F2) results in a longer duration of action and improved bioavailability such that the combined F1 and F2 results in improved bioavailability, wherein the drug is fentanyl.