Method of treating a disease condition susceptible to baclofen therapy

Abstract

The present invention discloses a method of treating a disease condition susceptible to baclofen therapy, said method comprising orally administering once-a-day in the evening a controlled release drug delivery system comprising baclofen or its pharmaceutically acceptable salt or its derivatives and pharmaceutically acceptable excipients.

1 . A method of treating a disease condition susceptible to baclofen therapy, said method comprising orally administering once-a-day in the evening a controlled release drug delivery system comprising baclofen or its pharmaceutically acceptable salt or its derivatives and pharmaceutically acceptable excipients. 
     
     
         2 . A method as claimed in  claim 1  wherein the disease condition is selected from the group consisting of spasticity, gastroparesis, gastroesophageal disorder, depression or other psychological conditions, alcohol related disorders such as alcohol dependence, smoking cessation, addiction liability of narcotic agents, emesis, cough, hiccoughs, neuropathic pain and musculoskeletal pain. 
     
     
         3 . A method of treating a disease condition susceptible to baclofen therapy;
 said method comprising orally administering once-a-day in the evening a gastric retention controlled release drug delivery system comprising baclofen or its pharmaceutically acceptable salt and pharmaceutically acceptable excipients.   
     
     
         4 . A method as claimed in  claim 3  wherein the disease condition is selected from the group consisting of spasticity, gastroparesis, gastroesophageal disorder, depression or other psychological conditions, alcohol related disorders such as alcohol dependence, smoking cessation, addiction liability of narcotic agents, emesis, cough, hiccoughs, neuropathic pain and musculoskeletal pain. 
     
     
         5 . A method as claimed in  claim 3  wherein the gastric retention controlled release drug delivery system swells in a dimensionally unrestrained manner to increase its size to promote gastric retention of the system in the stomach. 
     
     
         6 . A method of treating a disease condition susceptible to baclofen therapy;
 said method comprising orally administering once-a-day in the evening a gastric retention controlled release drug delivery system comprising baclofen or its pharmaceutically acceptable salt and pharmaceutically acceptable excipients wherein the gastric retention controlled release drug delivery system comprises a first composition having an immediately releasing fraction of the baclofen dose and a second composition having a slow release fraction of the baclofen dose wherein the first composition and the second composition occupy separate regions in the system, and at least one of the excipient in the controlled drug delivery system is selected from the group consisting of swellable polymer, gas generating agent, superdisintegrant and mixtures thereof, which excipient causes the system to swell in a dimensionally unrestrained manner to increase its size to promote gastric retention of the system in the stomach.   
     
     
         7 . A method as claimed in  claim 6  wherein the disease condition is selected from the group consisting of spasticity, gastroparesis, gastroesophageal disorder, depression or other psychological conditions, alcohol related disorders such as alcohol dependence, smoking cessation, addiction liability of narcotic agents, emesis, cough, hiccoughs, neuropathic pain and musculoskeletal pain. 
     
     
         8 . A method as claimed in  claim 1 , wherein the controlled release drug delivery system comprises baclofen or its pharmaceutically acceptable salt in amounts from equivalent to 5 mg to 80 mg of baclofen and pharmaceutically acceptable excipients. 
     
     
         9 . A method as claimed in  claim 1 , wherein upon multiple dose administration of the controlled drug delivery system the fluctuation index is less than 200. 
     
     
         10 . A method as claimed in  claim 9  wherein upon multiple dose administration of the controlled drug delivery system the fluctuation index is less than 170. 
     
     
         11 . A method as claimed in  claim 1 , wherein the method provides a bi-modal plasma concentration time profile. 
     
     
         12 . A method as claimed in  claim 1 , wherein the bi-modal plasma concentration time profile is such that the first plasma peak is obtained at an earlier time between 2 hours to 8 hours and the second peak is obtained at a time between 8 hours to 18 hours. 
     
     
         13 . A method as claimed in  claim 1 , wherein the bi-modal plasma concentration time profile is such that the first plasma peak is obtained at an earlier time between 2 hours to 4 hours and the second peak is obtained at a time between 10 hours to 14 hours. 
     
     
         14 . A method as claimed in  claim 3  wherein the gastric retention controlled release drug delivery system comprises a first composition having an immediately releasing fraction of the baclofen dose which is released within about 1 hour and a second composition having a slow release fraction of the baclofen dose wherein the first composition and the second composition occupy separate regions in the system, and at least one of the excipient in the controlled drug delivery system is selected from the group consisting of swellable polymer, gas generating agent, superdisintegrant and mixtures thereof, which excipient causes the system to swell in a dimensionally unrestrained manner to increase its size to promote gastric retention of the system in the stomach. 
     
     
         15 . A method as claimed in  claim 14  wherein the swelling index of the gastric retention controlled release drug delivery system ranges at 6 hours upon contact with an aqueous environment ranges from about 5 to about 15. 
     
     
         16 . A method as claimed in  claim 14  wherein the ratio of the fraction of total dose of baclofen present in the first composition to the second composition ranges from about 1:1 to 1:3. 
     
     
         17 . A method as claimed in  claim 14  wherein the ratio of the fraction of total dose of baclofen present in the first composition to the second composition ranges from about 1:1 to 1:1.5. 
     
     
         18 . A method as claimed in  claim 6  wherein the second composition is filled into capsules and the first composition surrounds the capsules. 
     
     
         19 . A method as claimed in  claim 18  wherein the swelling index of capsules of the gastric retention controlled release drug delivery system ranges at 6 hours upon contact with an aqueous environment ranges from about 6 to about 12. 
     
     
         20 . A method as claimed in  claim 6  wherein the second composition is a compressed core and the first composition surrounds the compressed core. 
     
     
         21 . A method as claimed in  claim 6  wherein the second composition includes at least two separate regions, a first region comprising baclofen or its pharmaceutically acceptable salt or its derivatives and a second region comprising the excipient selected from the group consisting of swellable polymers, gas generating agents, superdisintegrants and mixtures thereof. 
     
     
         22 . A method as claimed in  claim 6  wherein the excipient selected from the group consisting of swellable polymers, gas generating agents, superdisintegrants and mixtures thereof is also present in the first region. 
     
     
         23 . A method as claimed in  claim 18  wherein a third composition is present in between the first composition and the second composition. 
     
     
         24 . A method as claimed in  claim 23  wherein a third composition is in the form of a film of a water insoluble polymer and one or more excipients selected from the group consisting of swellable polymers, gas generating agents, super-disintegrants and mixtures thereof. 
     
     
         25 . A method as claimed in  claim 24  wherein the film has a tensile strength and elasticity sufficient to allow it to expand. 
     
     
         26 . A method as claimed in  claim 25  wherein the water insoluble polymer is selected from the group consisting of ethyl cellulose, methacrylic acid-ethyl acrylate copolymers, polyacrylic acid and mixtures thereof. 
     
     
         27 . A method as claimed in  claim 26  wherein the third composition is applied to the second composition in the form of a coating surrounding the second composition. 
     
     
         28 . A method as claimed in  claim 6  wherein the second composition comprises a hydrophobic material selected from the group consisting of waxes, oils, fatty acid and mixtures thereof. 
     
     
         29 . A method as claimed in  claim 6  wherein the second composition comprises water soluble materials. 
     
     
         30 . A method as claimed in  claim 6  wherein the weight ratio of second region of the second composition to the first region of the second composition is about 25:1. 
     
     
         31 . A method as claimed in  claim 6  wherein the weight ratio of third composition to the second composition is about 25:1. 
     
     
         32 . A controlled release drug delivery system comprising baclofen or a pharmaceutically acceptable salt thereof or its derivatives and pharmaceutically acceptable excipients for the use in the treatment by oral dosage once a day in the evening of the signs and symptoms of spasticity. 
     
     
         33 . A controlled release oral drug delivery system comprising baclofen or its pharmaceutically acceptable salts or its derivatives and pharmaceutically acceptable excipients for use in treating a disease condition wherein the oral drug delivery system is administered in the evening.