Claims
- 1. A formulation for systemic delivery of a protein selected from the group consisting of human growth hormone and human parathyroid hormone to a patient through the buccal mucosa, the formulation comprising:
a suspension of dehydrated solid particles in a delivery medium wherein the solid particles comprise a dehydration product of the pharmaceutical agent and an orally effective nonsteroidal membrane-permeation enhancer, the delivery medium comprising a fluid, the dehydrated solid particles being suspended in the delivery medium, and adapted for spray delivery of the dehydrated solid particles to the buccal mucosa.
- 2. The formulation of claim 1, said dehydrated solid particles further comprising a surfactant.
- 3. The formulation of claim 2, said dehydrated solid particles comprising a dehydration product of a substantially homogeneous mixture of said protein, at least one buffer, at least one surfactant, and the membrane-permeation enhancer.
- 4. The formulation of claim 2 in which said surfactant is selected from a group consisting of sorbitan monooleate, sorbitan monolaurate, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monooleate, polyoxyethylene ethers, dioctyl sodium sulfosuccinate, and polyoxyethylene block copolymers.
- 5. The formulation of claim 2 comprising about 0.01 to 20% by weight surfactant; about 0.1 to 80% by weight membrane-permeation enhancer; and the delivery medium comprises about 50 to 99% by weight propellant and about 5 to 20% by weight ethanol.
- 6. The formulation of claim 2 in which the dehydrated solid particles comprise a freeze-dried dehydration product of a mixture consisting essentially of the pharmaceutical agent in buffer, a surfactant, and the membrane-permeation enhancer.
- 7. The formulation of claim 1 wherein a substantial percentage of said dehydrated solid particles are greater than at least about 10 microns in diameter.
- 8. The formulation of claim 1, said delivery medium comprising a nonaqueous propellant for aerosol delivery of the dehydrated solid particles to the buccal mucosa.
- 9. The formulation of claim 1 adapted for aerosol delivery to the buccal mucosa wherein said protein is substantially absorbed without reaching the pulmonary region.
- 10. The formulation of claim 1, the delivery medium comprising a non-aqueous pharmaceutically acceptable propellant and a co-solvent selected from the group consisting of ethanol, glycerol, propylene glycol, sorbitol, vitamin E, and polyvinylpyrrolidone.
- 11. The formulation of claim 2 comprising a delivery medium further containing a non-aqueous pharmaceutically-acceptable propellant and an alcoholic cosolvent and said dehydrated solid particles comprising human growth hormone or human parathyroid hormone, said permeation enhancer and a pharmaceutically acceptable buffer.
- 12. The formulation of claim 1 in which the membrane-permeation enhancer is selected from a group consisting of sodium lauryl sulfate, sodium laurate, palmitoyl carnitin, Laureth-9, phosphatidylcholine, cyclodextrin, oleic acid, lauric acid, acylcarnitines, benz-alkonium chloride, benzethonium chloride, sodium salicylate, chlorobutanol, octoxynol-9, benzyl alcohol.
- 13. The formulation of claim 1 wherein a substantial percentage of said dehydrated solid particles are sized greater than about 10 μm and less than about 500 μm in diameter.
- 14. The formulation of claim 1 wherein a substantial percentage of said dehydrated solid particles are sized greater than about 10 μm and less than about 200 μm in diameter.
- 15. A formulation according to claim 1 wherein the protein is human growth hormone.
- 16. A formulation according to claim 1 wherein the protein is human parathyroid hormone.
- 17. A formulation according to claim 11 wherein the protein is human growth hormone.
- 18. A formulation according to claim 11 wherein the protein is human parathyroid hormone.
RELATED APPLICATIONS
[0001] This is a continuation-in-part of Ser. No. 09/586,007 filed Jun. 2, 2000 which claims the benefit of provisional application Serial No. 60/137,562 filed Jun. 4, 1999. The application also is related to U.S. patent application Ser. No. 09/944,492, filed Aug. 30, 2001 which is a continuation of, U.S. patent application Ser. No. 09/502,871, filed Feb. 11, 2000, which is incorporated herein by reference.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60137562 |
Jun 1999 |
US |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
09586007 |
Jun 2000 |
US |
Child |
10222058 |
Aug 2002 |
US |