Transmucosal hormone delivery system
The present invention provides a pharmaceutical composition for sublingual or buccal administration of actives with low to poor aqueous solubility, e.g. the hormone estradiol, which contains a solution of the active in a pharmaceutically acceptable solvent adsorbed or absorbed onto particles of a pharmaceutically acceptable carrier and methods of preparing and using the pharmaceutical composition.
1. A pharmaceutical composition containing estradiol in a solid dosage form for buccal or sublingual delivery, comprising:
estradiol;
a solvent into which estradiol is solvated; and
a solid adsorbent onto which the solvated estradiol is adsorbed,
the estradiol being in solution in the solid dosage form of the pharmaceutical composition.
2. The pharmaceutical composition of claims 1 , further comprising a solid water-soluble excipient, a disintegrant, a lubricant, or mixtures thereof.
3. The pharmaceutical composition of claim 1 , wherein estradiol is present at from about 0.05 mg to about 2.0 mg; the solvent is present at about 1 mg to about 50 mg; and the adsorbent is present at about 0.1 mg to about 50 mg.
4. The pharmaceutical composition of claim 2 , wherein the water-soluble excipient is present at about 25 mg to about 500 mg.
5. The pharmaceutical composition of claim 2 , wherein the disintegrant is present at about 0.5 mg to about 50 mg.
6. The pharmaceutical composition of claim 2 , wherein the lubricant is present at about 0.1 mg to about 15.0 mg.
7. The pharmaceutical composition of claim 1 , wherein the solvent comprises ethanol, ethyl acetate, isopropyl alcohol, triacetin, triethyl citrate, tributyl citrate, substituted polyethylene glycols, bisabolol, glycerin, mineral oil, ethyl oleate, oleic acid, fatty acid esters, squalane, animal oils, vegetable oils, propylene glycol, hydrogenated vegetable oils, isopropyl myristate, isopropyl palmitate, glycofurol, terpenes, essential oils, alcohols, polyols, silicone fluid and mixtures thereof.
8. The pharmaceutical composition of claim 1 , wherein the solid adsorbent comprises microcrystalline cellulose, cellulose powder, silicified microcrystalline cellulose, silica, clay, talc, starch, pregelatinized starch, calcium carbonate, magnesium carbonate, or mixtures thereof.
9. The pharmaceutical composition of claim 2 , wherein the solid water-soluble excipient comprises a sugar, a polyol, a saccharide, a polysaccharide, a dextrate, a dextrin, dextrose, fructose, lactitol, lactose, erythritol, maltose, maltitol, a maltodextrin, a polydextrose, trehalose, mannitol, a polyethylene glycol, sorbitol, sucrose, xylitol or mixtures thereof.
10. The pharmaceutical composition of claim 2 , wherein the disintegrant comprises sodium starch glycolate, crospovidone, croscarmellose sodium, low-substituted hydroxypropyl cellulose, starch, microcrystalline cellulose or mixtures thereof.
11. The pharmaceutical composition of claim 2 , wherein the lubricant comprises sodium stearyl fumarate, magnesium stearate, stearic acid, sodium lauryl sulfate, talc, polyethylene glycol, calcium stearate or mixtures thereof.
12. The pharmaceutical composition of claim 7 , wherein the solvent comprises a polyethylene glycol.
13. The pharmaceutical composition of claim 8 , wherein the adsorbent comprises a silica.
14. The pharmaceutical composition of claim 9 , wherein the excipient comprises mannitol.
15. The pharmaceutical composition of claim 10 , wherein the disintegrant comprises sodium starch glycolate.
16. The pharmaceutical composition of claim 11 , wherein the lubricant comprises sodium stearyl fumarate.
17. A method for increasing oral absorption and bioavailability while shortening onset of estradiol action in an oral solid dosage form comprising: providing estradiol in an amount of about 0.05 mg to about 2 mg; providing a liquid PEG in an amount of about 1 mg of to about 50 mg; providing a solid adsorbent in an amount up to about 50 mg; providing a co-solvent in an amount up to about 25 mg; providing a solid water-soluble excipient in an amount of about 25 mg to about 500 mg; providing a disintegrant in an amount of about 0.5 mg to about 50 mg; providing a lubricant in an amount of about 0.1 mg to about 15 mg; and forming a solid oral dosage for buccal or sublingual administration having increased oral absorption and bioavailability and shortened onset of action for estradiol.
18. A method for treating low estrogen levels and other disease states for which estradiol is an effective therapeutic, in a patient in need thereof, comprising: buccally or sublingually administering the estradiol-containing pharmaceutical composition in accordance with claim 1 , to the patient, such that a therapeutically effective amount of estradiol is administered.
19. A method for treating low estrogen levels and other disease states for which estradiol is an effective therapeutic, in a patient in need thereof, comprising: buccally or sublingually administering the estradiol-containing pharmaceutical composition in accordance with claim 2 , to the patient, such that a therapeutically effective amount of estradiol is administered.