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 gastric retentive dosage form comprising, a dose of acamprosate or a pharmaceutically acceptable salt thereof dispersed in a polymeric matrix wherein the polymeric matrix comprises one or more polymers that upon imbibition of fluid swells to a size sufficient to promote gastric retention, wherein upon administration to the subject, the gastric retentive dosage form provides a mean AUC of plasma acamprosate greater than the mean AUC of plasma acamprosate provided by an immediate release (IR) dosage form which contains a dose of acamprosate or pharmaceutically acceptable salt thereof equal to or more than the dose of acamprosate in the gastric retentive dosage form. 
     
     
         2 . The dosage form of  claim 1 , wherein the gastric retentive dosage form provides a mean AUC of plasma acamprosate which is about 110% to about 200% of the mean AUC of plasma acamprosate provided by the IR dosage form of equal or greater dose. 
     
     
         3 . The dosage form of  claim 1 , wherein the gastric retentive dosage form provides a mean C max  of plasma acamprosate which is about 60% to 70% of the mean C max  of plasma acamprosate provided by the IR dosage form. 
     
     
         4 . The dosage form of  claim 1 , wherein the gastric retentive dosage form provides a T max  which is about 4 hours to 7 hours greater than the T max  provided by the IR dosage form. 
     
     
         5 . The dosage form of  claim 1 , wherein administration to a subject in a fed mode results in a decrease in mean AUC of plasma acamprosate which is less than the AUC when the dosage form is administered to the subject in a fasted state. 
     
     
         6 . The dosage form of  claim 1 , wherein the side effects of the gastric retentive dosage form having no enteric coating are equal to or less than the immediate release dosage form. 
     
     
         7 . The dosage form of  claim 1 , wherein the dose of acamprosate is about 200 mg to about 1000 mg. 
     
     
         8 . The dosage form of  claim 1 , wherein not less than about 60% of the dose of acamprosate is released from the gastric retentive dosage form after about 6 hours after exposure to fluid. 
     
     
         9 . The dosage form of  claim 1 , wherein the at least one or more polymers is a polyethylene glycol. 
     
     
         10 . A method for administering a therapeutically effective amount of acamprosate to a subject, comprising administering to the subject acamprosate or a pharmaceutically acceptable salt thereof dispersed in a gastric retained dosage form to the subject in which a fed mode has been induced and wherein the dosage form comprises a single polymer matrix comprising at least one swellable hydrophilic polymer that swells in a dimensionally unrestrained manner by imbibing water to increase its size to promote gastric retention of the dosage form in the stomach of the subject, wherein upon contact with aqueous fluid, at least about 80% of the acamprosate in the extended release portion of the dosage form is released by the dosage form over a period of at least about 5 hours. 
     
     
         11 . The method of  claim 10 , wherein the acamprosate is administered in a daily dose of about 300 mg to about 1000 mg. 
     
     
         12 . The method of  claim 10 , wherein the gastric retained dosage form provides a mean AUC of plasma acamprosate greater than the mean AUC of plasma acamprosate provided by an immediate release (IR) dosage form which contains a dose of acamprosate or pharmaceutically acceptable salt thereof equal to or less than the dose of acamprosate in the gastric retentive dosage form. 
     
     
         13 . The method of  claim 12 , wherein said dose is administered with a meal. 
     
     
         14 . The method of  claim 10 , wherein the gastric retentive dosage form provides a mean C max  of plasma acamprosate which is about 60% to 70% of the mean C max  of plasma acamprosate provided by an IR dosage form which contains a dose of acamprosate or pharmaceutically acceptable salt thereof equal to or less than the dose of acamprosate in the gastric retentive dosage form. 
     
     
         15 . The method of  claim 10 , wherein the gastric retained dosage form provides a T max  which is about 4 hours to 7 hours greater than the T max  provided by an IR dosage form which contains a dose of acamprosate or pharmaceutically acceptable salt thereof equal to or less than the dose of acamprosate in the gastric retentive dosage form. 
     
     
         16 . A method for treating a subject suffering from alcohol dependence comprising administering to the subject a total daily dose of about 300 to 2500 mg acamprosate or a pharmaceutically acceptable salt thereof dispersed in a polymeric matrix wherein the polymeric matrix comprises one or more polymers that upon imbibition of fluid swells to a size sufficient to promote gastric retention, wherein upon administration to the subject, the gastric retentive dosage form provides a mean AUC of plasma acamprosate greater than the mean AUC of plasma acamprosate provided by an immediate release (IR) dosage form which contains a dose of acamprosate or pharmaceutically acceptable salt thereof equal to or more than the dose of acamprosate in the gastric retentive dosage form. 
     
     
         17 . The method of  claim 15 , wherein the acamprosate is administered in a total daily dose of about 300 mg to 1000 mg 
     
     
         18 . The method of  claim 15 , wherein said dose is administered twice in a 24-hour period. 
     
     
         19 . The method of  claim 15 , wherein said dose is administered once in a 24-hour period. 
     
     
         20 . The method of  claim 11 , wherein said dose is administered with a meal. 
     
     
         21 . A gastroretentive drug dosage form, comprising: acamprosate or a pharmaceutically acceptable salt thereof, formulated with an excipient that forms a matrix of one or more polymers and swells within the stomach to a size sufficient so that it remains within the stomach, and wherein upon administration to a patient the gastroretentive dosage form achieves a mean AUC for acamprosate that is greater than the mean AUC for an immediate release (IR) composition of the same dose of acamprosate. 
     
     
         22 . The method of  claim 21 , wherein the gastroretentive dosage form achieves a mean AUC for acamprosate that is about 110% to about 200% of the mean AUC for an IR composition of the same dose of acamprosate. 
     
     
         23 . The method of  claim 21 , wherein the gastroretentive dosage form achieves a mean AUC for acamprosate that is greater than the mean AUC for an IR composition of the same dose of acamprosate. 
     
     
         24 . The gastroretentive dosage form of  claim 21 , wherein the gastroretentive dosage form achieves a C max  for acamprosate that is about 60% to 70% of the C max  for an immediate release composition. 
     
     
         25 . The gastroretentive dosage form of  claim 21 , wherein the gastroretentive dosage form achieves a C max  for acamprosate that is less than the C max  for an immediate release composition. 
     
     
         26 . The gastroretentive dosage form of  claim 21 , wherein the gastroretentive dosage form achieves a T max  for acamprosate that is about 4 hours to 7 hours greater than the T max  for an immediate release composition. 
     
     
         27 . The gastroretentive dosage form of  claim 21 , wherein the gastroretentive dosage form achieves a T max  for acamprosate that is longer compared to the T max  for an immediate release composition. 
     
     
         28 . The gastroretentive dosage form of  claim 21 , wherein the dosage form is formulated for administration to a patient in a fed state, and wherein upon administration to said patient in a fed state the dosage form achieves a mean AUC for acamprosate that is greater than the mean AUC for an immediate release (IR) composition. 
     
     
         29 . The gastroretentive dosage form of  claim 21 , wherein the gastric retentive form causes less gastro intestinal side effects than the immediate-release form of acamprosate. 
     
     
         30 . The gastroretentive dosage form of  claim 21 , wherein the dosage of acamprosate or the salt is less than 1 gram. 
     
     
         31 . The gastroretentive dosage form of  claim 21 , wherein the dosage of acamprosate or the salt between 100 mg and 800 mg. 
     
     
         32 . The gastroretentive dosage form of  claim 21 , wherein more than 50% of the acamprosate is within 6 hours of administration. 
     
     
         33 . The gastroretentive dosage form of  claim 32 , wherein more than 60% of the acamprosate is released within 6 hours of administration. 
     
     
         34 . The gastroretentive dosage form of  claim 21 , further comprising polyethylene glycol. 
     
     
         35 . The gastroretentive dosage form of  claim 21 , wherein the dosage form comprises one or more of Carbopol 974P (carbomer homopolymer type B) and carboxymethylcellulose. 
     
     
         36 . The gastroretentive dosage form of  claim 21 , wherein the dosage form is a tablet, a pill, a spheroid tablet or pill, or a capsule. 
     
     
         37 . A method of administering a therapeutically effective amount of a daily dose of acamprosate comprising administering acamprosate or a pharmaceutically acceptable salt thereof to a patient in need thereof, which patient has been induced to be in a fed mode, and the administered acamprosate is in a composition comprising a matrix comprising a polymer that swells within the stomach to a size sufficient so that it remains within the stomach, the polymer comprising a hydrophilic polymer, wherein the composition is formulated to release acamprosate at a controlled rate, and formulated to release at least 50% of the acamprosate within the stomach of the recipient within 4-8 hours of delivery. 
     
     
         38 . The method of  claim 37 , wherein the composition is formulated to release acamprosate at a controlled rate, and is formulated to release at least 80% of the acamprosate within the stomach of the recipient within five hours of delivery. 
     
     
         39 . The method of  claim 37 , wherein the acamprosate or the salt is in a dosage of 300 mg to about 3 grams. 
     
     
         40 . The method of  claim 37 , wherein the acamprosate or the salt is in a dosage of less than 1 gram. 
     
     
         41 . The method of  claim 37 , wherein the acamprosate or the salt is in a dosage of about 100 to 800 mg. 
     
     
         42 . The method of  claim 37 , wherein the administered acamprosate composition achieves a mean AUC for acamprosate that is greater than the mean AUC for an immediate release composition of a acamprosate of the same amount. 
     
     
         43 . The method of  claim 37 , wherein the administered acamprosate composition achieves a C max  for acamprosate that is less than the C max  for an immediate release composition. 
     
     
         44 . The method of  claim 37 , wherein the administered acamprosate composition achieves a C max  for acamprosate that is about 60% to 70% of the C max  for an immediate release composition. 
     
     
         45 . The method of  claim 37 , wherein the administered acamprosate composition achieves a T max  for acamprosate that is longer compared to the T max  for an immediate release composition. 
     
     
         46 . The method of  claim 37 , wherein the administered gastroretentive dosage form achieves a T max  for acamprosate that is about 3 hours to 8 hours greater than the T max  for an immediate release composition. 
     
     
         47 . The method of  claim 37 , wherein the acamprosate is administered to a patient suffering from a neuropsychiatric disorder. 
     
     
         48 . The method of  claim 47 , 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). 
     
     
         49 . The method of  claim 37 , wherein the acamprosate composition comprises one or more of Carbopol 974P (carbomer homopolymer type B) and carboxymethylcellulose. 
     
     
         50 . The method of  claim 37 , wherein the acamprosate composition is formed into a tablet, a pill, a spheroid tablet or pill, or a capsule. 
     
     
         51 . A method of treating alcohol dependence, comprising administering an effective amount of a pharmaceutical formulation comprising acamprosate or a pharmaceutically acceptable salt to a patient in need thereof, in whom a fed mode has been induced, wherein the formulation is formulated with one or more gastroretentive technologies configured to swell or expand, and formulated with a controlled release technology comprising a matrix, the matrix comprising one or more polymers, and wherein the administered formulation achieves a mean AUC for acamprosate that is greater than the mean AUC for an immediate release composition of a acamprosate. 
     
     
         52 . The method of  claim 51 , wherein the acamprosate is in an amount of 300 mg to 2500 mg. 
     
     
         53 . The method of  claim 51 , wherein the acamprosate is in an amount of less than 1 gram. 
     
     
         54 . The method of  claim 51 , wherein the acamprosate is in an amount between 300 mg and 800 mg. 
     
     
         55 . The method of  claim 51 , wherein the formulation is administered twice daily. 
     
     
         56 . The method of  claim 51 , wherein the formulation is administered once daily. 
     
     
         57 . The method of  claim 51 , wherein the formulation comprises one or more of Carbopol 974P (carbomer homopolymer type B) and carboxymethylcellulose. 
     
     
         58 . The method of  claim 51 , wherein the formulation is formed into a tablet, a pill, a spheroid tablet or pill, or a capsule.