Sustained release lingual thioctic acid delivery systems

Abstract

The invention provides new methods of administering alpha-lipoic acid to patients. A diffusion rate limiting matrix is utilized to buccally, lingually and/or sublingually deliver the alpha-lipoic acid. This sustained release matrix is intended for general nutritional supplementation and/or the treatment of various physiological disorders, such as diabetic neuropathy. Due to its lingual nature, this rate limiting matrix can deliver approximately IV-equivalent plasma levels of thioctic acid and is not meant to be swallowed.

1 . A method of screening patients to select a dissolvable alpha-lipoic acid tablet composition made without heating the ingredients of the tablet formulation to a temperature at which any ingredient of the tablet composition melts, for treating a disease or condition treatable by an increased concentration of alpha-lipoic acid in the circulation, the method comprising:
 a. administering to a patient a first orally dissolvable tablet composition, the tablet composition being an orally dissolvable sustained release formulation comprising alpha-lipoic acid wherein the alpha-lipoic acid release comprises a first and a second peak release rate;   b. directing the patient to fully dissolve the first tablet composition in the patient's mouth;   c. evaluating the patient's tolerance to said first tablet composition;   d. administering to the same patient one or more additional sustained release, orally dissolvable tablet compositions containing a different amount of alpha-lipoic acid than that in the first tablet composition, a different release limiting formulation than that of the first tablet composition, or both, each additional tablet composition administered to the patient one tablet at a time and separate from any other tablet composition;   e. directing the patient to fully dissolve each additional tablet composition in their mouth, one at a time;   f. evaluating the patient's tolerance to each additional tablet composition; and   g. prescribing to the patient a course of treatment comprising administering one or more types of orally dissolvable, sustained release, tablet compositions comprising a first and a second peak release rate based upon the patient's disease or condition and the patient's response to the first tablet composition and the one or more additional tablet compositions.   
     
     
         2 . The method of  claim 1 , wherein the rate of release of alpha lipoic acid from the one or more tablet compositions administered after the first tablet composition differs from the release rate of alpha-lipoic acid from the first tablet composition and comprises a first and a second peak release rate of alpha-lipoic acid. 
     
     
         3 . The method of  claim 1 , wherein the concentration of alpha-lipoic acid in the one or more tablet compositions administered after the first tablet composition differs from the concentration of alpha-lipoic acid in the first tablet composition. 
     
     
         4 . The method of  claim 1 , wherein both the rate of release of alpha lipoic acid from, and the concentration of alpha-lipoic acid in, the one or more tablet compositions administered after the first tablet composition differs from the rate of release of alpha-lipoic acid from, and the concentration of alpha lipoic acid in, the first tablet composition, wherein the sustained release of alpha-lipoic acid from each tablet composition administered after the first tablet composition comprises a first and a second peak release rate. 
     
     
         5 . The method of  claim 1 , wherein the prescribed course of treatment comprises at least one tablet composition comprising alpha-lipoic acid having the highest concentration of alpha-lipoic acid that the patient can tolerate, the fastest release rate of alpha-lipoic acid that the patient can tolerate, or both the highest concentration of alpha-lipoic acid and the fastest release rate of alpha-lipoic acid that the patient can tolerate, based on the level of burning sensation experienced by the patient at a given alpha-lipoic acid concentration, alpha-lipoic acid release rate, or combination of alpha-lipoic acid concentration and release rate. 
     
     
         6 . The method of  claim 1 , wherein the method comprises considering the pain or discomfort experienced by a patient due to a disease or condition treatable by alpha-lipoic acid administration and providing patients experiencing greater levels of disease-related or condition-related pain or discomfort than the disease-related or condition-related pain or discomfort experienced by another patient one or more tablet compositions comprising a higher concentration of alpha-lipoic acid, a faster release rate of alpha-lipoic acid, or both a higher concentration and a faster release rate of alpha-lipoic acid than that of tablet compositions provided to patients experiencing lower levels of disease-related or condition-related pain or discomfort. 
     
     
         7 . The method of  claim 6 , wherein the disease or condition is selected from a group comprising general nutritional deficiency, Alzheimer's disease, diabetic neuropathy, and retinal neuropathies. 
     
     
         8 . The method of  claim 7 , wherein the disease or condition is diabetic peripheral neuropathy. 
     
     
         9 . A method of increasing the concentration of alpha-lipoic acid in an individual comprising (a) delivering a dissolvable, compressed tablet, made without the application of heat to a temperature at which any ingredient in the compressed tablet melts, comprising alpha-lipoic acid in a concentration of 7.5-27%, to the mouth of the individual such that dissolving the dissolvable, compressed tablet in the mouth results in a variable sustained release profile comprising a first and a second peak release rate of alpha-lipoic acid from the dissolvable, compressed tablet, and (b) maintaining the compressed tablet in the mouth of the individual until the compressed tablet is fully dissolved without the individual experiencing a burning sensation which causes the individual to be unable to maintain the compressed tablet in their mouth until the compressed tablet is fully dissolved. 
     
     
         10 . The method of  claim 9 , wherein the alpha-lipoic acid is racemic ALA. 
     
     
         11 . The method of  claim 9 , wherein administration of the compressed tablet results in the blood concentration of alpha-lipoic acid in the individual reaching at least 65% of the concentration achieved by intravenous administration of the same amount of alpha-lipoic acid. 
     
     
         12 . The method of  claim 9 , wherein the alpha-lipoic acid in the compressed tablet is in a concentration of 9-27%, and the average response in a population of at least 12 test subjects is that the compressed tablet is acceptable for daily use despite any irritation incurred in fully dissolving the tablet in the mouth. 
     
     
         13 . The method of  claim 12 , wherein administration of the compressed tablet results in the blood concentration of alpha-lipoic acid in the individual reaching at least 65% of the concentration achieved by intravenous administration of the same amount of alpha-lipoic acid. 
     
     
         14 . The method of  claim 10 , wherein the alpha-lipoic acid in the compressed tablet is in a concentration of 9-27%, and the average response in a population of at least 12 test subjects is that the compressed tablet is acceptable for daily use despite any irritation incurred in dissolving the tablet in the mouth. 
     
     
         15 . The method of  claim 10 , wherein administration of the compressed tablet results in the blood concentration of alpha-lipoic acid in the individual reaching at least 65% of the concentration achieved by intravenous administration of the same amount of alpha-lipoic acid. 
     
     
         16 . The method of  claim 13 , wherein administration of the compressed tablet results in the blood concentration of alpha-lipoic acid in the individual reaching at least 85% of the concentration achieved by intravenous administration of the same amount of alpha-lipoic acid. 
     
     
         17 . The method of  claim 11 , wherein administration of the compressed tablet results in the blood concentration of alpha-lipoic acid in the individual reaching at least 85% of the concentration achieved by intravenous administration of the same amount of alpha-lipoic acid. 
     
     
         18 . The method of  claim 15 , wherein administration of the compressed tablet results in the blood concentration of alpha-lipoic acid in the individual reaching at least 85% of the concentration achieved by intravenous administration of the same amount of alpha-lipoic acid.