Acamprosate formulations, methods of using the same, and combinations comprising the same

Abstract

Embodiments disclosed herein generally relate to acamprosate formulations, methods of use of the formulations, to methods of using the formulations in combination with at least one other medication, and to combination products and compositions comprising the formulations and at least one other medication, such as neuroleptic (antipsychotic) and/or antidepressant drugs.

What is claimed is: 
     
         1 . A method of treating a neuropsychiatric disorder comprising administering to a patient in need thereof a total daily dosage of acamprosate of less than 1000 mg, wherein the acamprosate is administered once or twice daily to achieve the total daily dosage, and the administered acamprosate is in a composition that is formulated to release acamprosate at a controlled rate, and formulated to release less than 50% of the acamprosate within the stomach of the recipient within the first two hours after delivery and to release greater than 50% of the acamprosate within the stomach within six hours of delivery. 
     
     
         2 . The method of  claim 1 , wherein the composition comprises one or more gastric retentive excipients, one or more controlled release excipients or one or more gastric retentive excipients and one or more controlled release excipients. 
     
     
         3 . The method of  claim 1 , wherein the administered composition is formulated to achieve a mean AUC for acamprosate that is greater than the mean AUC for an immediate release composition of a acamprosate, to have a C max  for acamprosate that is less than the C max  for an immediate release composition, and/or to have a T max  for acamprosate that is longer than the T max  for an immediate release composition. 
     
     
         4 . The method of  claim 2 , wherein the composition comprises one or more of Carbopol 974P (carbomer homopolymer type B) and carboxymethylcellulose. 
     
     
         5 . The method of  claim 1 , wherein the acamprosate is administered once daily. 
     
     
         6 . The method of  claim 1 , wherein the acamprosate is administered twice daily. 
     
     
         7 . The method of  claim 1 , further comprising administering the acamprosate to a patient in a fed state or inducing a fed state in the patient. 
     
     
         8 . The method of  claim 1 , wherein the neuropsychiatric disorder is selected from the group consisting of tardive dyskinesia and other movement disorders induced by chronic exposure of patients to neuroleptic (antipsychotic) drugs, peak-dose dyskinesia associated with Parkinson's disease treated with levodopa, Tourette syndrome, posttraumatic stress disorder (PTSD), alcohol dependence and obsessive-compulsive disorder (OCD). 
     
     
         9 . The method of  claim 1 , further comprising administering at least a second medication that comprises one or more of a selective serotonin reuptake inhibitor (SSRI), and a serotonin-norepinephrine reuptake inhibitor (SNRI) 
     
     
         10 . The method of  claim 9 , wherein the SSRI or SNRI is selected from the group consisting of citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, paroxetine, sertraline, and venlafaxine. 
     
     
         11 . The method of  claim 1 , further comprising administering alpha lipoic acid or a salt or chelate of alpha lipoic acid in an amount of 50 mg to 600 mg. 
     
     
         12 . The method of  claim 11 , wherein the alpha lipoic acid is either racemic alpha lipoic acid, a racemic mixture enriched in R-alpha lipoic acid, R-alpha lipoic acid, or a salt or chelate of alpha lipoic acid that is a salt or chelate of either racemic alpha lipoic acid, a racemic mixture enriched in R-alpha lipoic acid, or R-alpha lipoic acid. 
     
     
         13 . A composition comprising acamprosate in a dosage of less than or equal to 900 mg that is formulated to retain the composition in the stomach of the recipient and to control the release of the acamprosate for a period of time sufficient to release less than 50% of the acamprosate from the composition into the stomach within a 2 hours after administration, and to release more than 50% of the acamprosate at a controlled rate within 6 hours of administration. 
     
     
         14 . The composition of  claim 13 , wherein the composition is formulated to release at least 90% of the acamprosate within 8 hours. 
     
     
         15 . The composition of  claim 3  wherein the composition comprises a gastric retentive technology, a controlled release technology, or both a gastric retentive and a controlled release technology. 
     
     
         16 . The composition of  claim 13 , wherein the composition comprises one or more of Carbopol 974P (carbomer homopolymer type B) and carboxymethylcellulose. 
     
     
         17 . The composition of  claim 13 , wherein the composition is formulated such that upon administration to a recipient the mean AUC for acamprosate is greater than the mean AUC for an immediate release composition of a acamprosate, the C max  for acamprosate is less than the C max  for an immediate release composition, and/or the T max  for acamprosate is longer than for immediate release acamprosate. 
     
     
         18 . The composition of  claim 13 , wherein the dosage of acamprosate is between 100 mg and 800 mg. 
     
     
         19 . The composition of  claim 13 , further comprising alpha lipoic acid, where the alpha lipoic acid is either racemic alpha lipoic acid, racemic alpha lipoic acid enriched in R-alpha lipoic acid or R-alpha lipoic acid, or a salt or a chelate of either racemic alpha lipoic acid, racemic alpha lipoic acid enriched in R-alpha lipoic acid or R-alpha lipoic acid, and the dosage of said alpha lipoic acid is between 50 mg and 600 mg. 
     
     
         20 . The composition of  claim 13 , further comprising at least a second medication that comprises one or more of a selective serotonin reuptake inhibitor (SSRI), and a serotonin-norepinephrine reuptake inhibitor (SNRI). 
     
     
         21 . The composition of  claim 20 , wherein the SSRI or SNRI is selected from the group consisting of citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, paroxetine, sertraline, and venlafaxine. 
     
     
         22 . The composition of  claim 21  wherein the dosage of the SSRI or SNRI is greater than or equal to one-half of its lowest approved dosage and less than or equal to its highest approved dosage. 
     
     
         23 . A combination product comprising acamprosate in a dosage of less than or equal to 900 mg and at least a second medication that comprises an antipsychotic (neuroleptic) medication, wherein the product formulated to be retained in the stomach of the recipient and to control the release of the acamprosate for a period of time sufficient to release less than 50% of the acamprosate from the composition into the stomach within a 2 hours after administration, and to release more than 50% of the acamprosate at a controlled rate within 6 hours of administration. 
     
     
         24 . The product of  claim 23 , wherein the product comprises a single dosage form unit comprising both acamprosate and the second medication. 
     
     
         25 . The product of  claim 23 , wherein the antipsychotic medication is a first or a second generation antipsychotic. 
     
     
         26 . The product of  claim 25 , wherein the first or a second generation antipsychotic is selected from the group consisting of thioridazine, chlorpromazine, thiothixene, trifluoperazine, fluphenazine, haloperidol, perphenazine, loxapine, molindone, metoclopramide, aripiprazole, asenapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone. 
     
     
         27 . The product of  claim 26 , wherein the dosage of the first-generation antipsychotic or second-generation antipsychotic is greater than or equal to one-half of its lowest approved dosage and less than or equal to its highest approved dosage. 
     
     
         28 . A method of treating a neuropsychiatric disorder comprising administering to a patient in need thereof the combination product of  claim 23 , wherein the total daily dosage of the acamprosate is less than 900 mg and the product is administered once or twice daily to achieve the total daily dosage. 
     
     
         29 . A method of reducing the risk or delaying the onset or diminishing the severity of tardive dyskinesia in a patient who requires antipsychotic medication, comprising administering to such a patient the combination product of  claim 23 , wherein the total daily dosage of the acamprosate is less than 900 mg and the product is administered once or twice daily to achieve the total daily dosage. 
     
     
         30 . A method of reducing anxiety in a patient receiving an antipsychotic, anti-anxiety or antidepressant medication, comprising, administering to a patient in need thereof the composition of  claim 20  or the combination product  claim 23 , wherein the total daily dosage of the acamprosate is less than 900 mg and the product is administered once or twice daily to achieve the total daily dosage.