Melatonin tablet and methods of preparation and use

Abstract

The present invention provides a pharmaceutical composition for sublingual or buccal administration of actives with low to poor aqueous solubility, e.g. the indole hormone melatonin, 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 solid dosage form for sublingual or buccal administration of a hormone having low to poor aqueous solubility, said dosage form comprising melatonin in a dissolved state, said dissolved melatonin being associated with a pharmaceutically acceptable carrier wherein the melatonin is in a dissolved state in the final dosage form. 
   
   
       2 . The dosage form of  claim 1  wherein the dissolve melatonin is coated, absorbed, or adsorbed onto said carrier. 
   
   
       3 . The dosage form of  claim 1  wherein the melatonin is dissolved in a pharmaceutically acceptable solvent selected from polyethylene glycol, ethanol, ethyl acetate, isopropyl alcohol, triacetin, triethyl citrate, tributyl citrate, substituted polyethylene glycols, propylene glycol, bisabolol, glycerin, mineral oil, ethyl oleate, oleic acid, oleyl alcohol fatty acid esters, squalane, animal oils, vegetable oils, hydrogenated vegetable oils, isopropyl myristate, isopropyl palmitate, glycofurol, terpenes, essential oils, alcohols, water, polyols, silicone fluids, glycerides, or a mixture thereof. 
   
   
       4 . The dosage form of  claim 3  in which the pharmaceutically acceptable solvent is polyethylene glycol. 
   
   
       5 . The dosage form of  claim 3 , in which the pharmaceutically acceptable solvent is a mixture of polyethylene glycol and oleic acid. 
   
   
       6 . The dosage form of  claim 1  in which the pharmaceutically acceptable carrier is selected from silica, microcrystalline cellulose, cellulose, silicified microcrystalline cellulose, clay, talc, starch, pregelatinized starch, calcium carbonate, calcium silicate, dicalcium phosphate, magnesium carbonate and mixtures thereof. 
   
   
       7 . A pharmaceutical composition as claimed in  claim 6 , in which the pharmaceutically acceptable carrier is silica. 
   
   
       8 . A pharmaceutical composition as claimed in  claim 7 , wherein the silica carrier are particles ranging in size from about 3 to about 30 microns. 
   
   
       9 . A pharmaceutical composition as claimed in  claim 1 , in which the concentration of melatonin in the solvent is in the range of about 5% to about 30% w/w. 
   
   
       10 . A pharmaceutical composition as claimed in  claim 1 , in which the weight:weight ratio of carrier to solution is in the range of about 1:0.5 to about 1:4. 
   
   
       11 . A pharmaceutical composition as claimed in  claim 1 , which further comprises a diluent. 
   
   
       12 . A pharmaceutical composition as claimed in  claim 1 , which further comprises a disintegrent. 
   
   
       13 . A pharmaceutical composition as claimed in  claim 1 , which further comprises a lubricant. 
   
   
       14 . A pharmaceutical composition as claimed in  claim 1 , which contains from about 0.01 to about 3 mg of melatonin per unit dose. 
   
   
       15 . A pharmaceutical composition as claimed in  claim 1 , which is in the form of a tablet. 
   
   
       16 . A process for the preparation of a pharmaceutical composition as defined in  claim 1 , which comprises the steps of
 dissolving melatonin in the pharmaceutically acceptable solvent to form a drug solution,   mixing the drug solution with particles of a pharmaceutically acceptable carrier to coat, adsorb or absorb said solution onto the carrier particles.   
   
   
       17 . A process as claimed in  claim 16 , in which the drug solution is further processed to provide a flowable powder. 
   
   
       18 . A process as claimed in  claim 16 , which further comprises adding additional excipients. 
   
   
       19 . A process of  claim 16 , wherein the process further comprises compressing the composition to form a tablet. 
   
   
       20 . A method of providing a patient with melatonin therapy, which comprises providing a dosage form of  claim 1 ; and administering said dosage form by a sublingual or buccal route to a patient in need of said therapy. 
   
   
       21 . A composition of  claim 1  wherein the hormone is selected from the group consisting of melatonin, estrogens, progesterone, testosterone, and dihydroxytestosterone.