Sustained release formulation of naltrexone

Abstract

A sustained-release oral dosage form of naltrexone or a pharmaceutically acceptable salt thereof is provided. The oral dosage form may be administered with another compound. Administration of the oral dosage form may reduce a side effect, which may be a side effect at least partially attributable to a weight-loss treatment. The oral dosage form may be administered to treat a weight-loss condition.

1 . (canceled) 
     
     
         2 . (canceled) 
     
     
         3 . A method of treating overweight or obesity comprising orally administering daily about 16 mg to about 32 mg of naltrexone and about 360 mg of bupropion, or pharmaceutically acceptable salts thereof, to a person in need thereof, wherein the bupropion or pharmaceutically acceptable salt thereof is administered as a sustained-release formulation, wherein the naltrexone or pharmaceutically acceptable salt thereof is administered as a sustained-release formulation, and wherein said sustained-release formulation of naltrexone has an in vitro naltrexone dissolution profile in a dissolution test of USP Apparatus 2 Paddle Method at 100 rpm in a dissolution medium of water at 37° C. of:
 a) about 39% and about 70% of naltrexone released in one hour; 
 b) about 62% and about 90% of naltrexone released in two hours; and 
 c) at least about 99% in 8 hours; 
 wherein about 8 mg or about 16 mg of said sustained-release formulation of naltrexone or a pharmaceutically acceptable salt thereof is administered twice daily, and about 180 mg of said sustained-release formulation of bupropion or a pharmaceutically acceptable salt thereof is administered twice daily. 
 
     
     
         4 . The method of  claim 3 , wherein said sustained-release formulation of naltrexone provides an in vivo plasma concentration profile of:
 a) a naltrexone C max  that is less than about 80% of the naltrexone C max  of an equal amount of immediate-release naltrexone hydrochloride; and   b) a naltrexone AUC last  that is about 80% and about 125% of the naltrexone AUC last  of an equal amount of immediate-release naltrexone hydrochloride.   
     
     
         5 . The method of  claim 3 , wherein said sustained-release formulation of naltrexone provides an in vivo plasma concentration profile of:
 a) a 6-beta naltrexol C max  that is less than about 80% of the 6-beta naltrexol C max  of an equal amount of immediate-release naltrexone hydrochloride; and   b) a 6-beta naltrexol AUC last  that is about 80% and about 125% of the 6-beta naltrexol AUC last  of an equal amount of immediate-release naltrexone hydrochloride.   
     
     
         6 . The method of  claim 3 , wherein said sustained-release naltrexone or pharmaceutically acceptable salt thereof and said sustained-release bupropion or pharmaceutically acceptable salt thereof are administered in a single oral unit dosage form. 
     
     
         7 . A method of treating overweight or obesity comprising orally administering daily about 16 mg to about 32 mg of naltrexone and about 360 mg of bupropion, or pharmaceutically acceptable salts thereof, to a person in need thereof, wherein the bupropion or pharmaceutically acceptable salt thereof is administered as a sustained-release formulation, wherein the naltrexone or pharmaceutically acceptable salt thereof is administered as a sustained-release formulation, and wherein said sustained-release formulation of naltrexone has an in vitro naltrexone dissolution profile in a dissolution test of USP Apparatus 2 Paddle Method at 100 rpm in a dissolution medium of water at 37° C. of:
 a) about 39% and about 70% of naltrexone released in one hour; 
 b) about 62% and about 90% of naltrexone released in two hours; and 
 wherein about 8 mg or about 16 mg of said sustained-release formulation of naltrexone or a pharmaceutically acceptable salt thereof is administered twice daily, and about 180 mg of said sustained-release formulation of bupropion or a pharmaceutically acceptable salt thereof is administered twice daily. 
 
     
     
         8 . The method of  claim 7 , wherein said sustained-release formulation of naltrexone provides an in vivo plasma concentration profile of:
 a) a naltrexone C max  that is less than about 80% of the naltrexone C max  of an equal amount of immediate-release naltrexone hydrochloride; and   b) a naltrexone AUC last  that is about 80% and about 125% of the naltrexone AUC last  of an equal amount of immediate-release naltrexone hydrochloride.   
     
     
         9 . The method of  claim 7 , wherein said sustained-release formulation of naltrexone provides an in vivo plasma concentration profile of:
 a) a 6-beta naltrexol C max  that is less than about 80% of the 6-beta naltrexol C max  of an equal amount of immediate-release naltrexone hydrochloride; and   b) a 6-beta naltrexol AUC last  that is about 80% and about 125% of the 6-beta naltrexol AUC last  of an equal amount of immediate-release naltrexone hydrochloride.   
     
     
         10 . The method of  claim 7 , wherein said sustained-release naltrexone or pharmaceutically acceptable salt thereof and said sustained-release bupropion or pharmaceutically acceptable salt thereof are administered in a single oral unit dosage form. 
     
     
         11 . A method of treating overweight or obesity comprising orally administering daily about 16 mg to about 32 mg of naltrexone and about 360 mg of bupropion, or pharmaceutically acceptable salts thereof, to a person in need thereof, wherein the bupropion or pharmaceutically acceptable salt thereof is administered as a sustained-release formulation, wherein the naltrexone or pharmaceutically acceptable salt thereof is administered as a sustained-release formulation, and wherein said sustained-release formulation of naltrexone has an in vitro naltrexone dissolution profile in a dissolution test of USP Apparatus 2 Paddle Method at 100 rpm in a dissolution medium of water at 37° C. of:
 a) about 67% to about 80% of naltrexone released in 1 hour; and 
 b) about 85% to about 96% of naltrexone released in 2 hours; and 
 c) at least about 99% of naltrexone released in 8 hours; 
 wherein about 8 mg or about 16 mg of said sustained-release formulation of naltrexone or a pharmaceutically acceptable salt thereof is administered twice daily, and about 180 mg of said sustained-release formulation of bupropion or a pharmaceutically acceptable salt thereof is administered twice daily. 
 
     
     
         12 . The method of  claim 11 , wherein said sustained-release naltrexone or pharmaceutically acceptable salt thereof and said sustained-release bupropion or pharmaceutically acceptable salt thereof are administered in a single oral unit dosage form. 
     
     
         13 . The method of  claim 11 , wherein said sustained-release formulation of naltrexone provides an in vivo plasma concentration profile of:
 a) a naltrexone C max  that is less than about 80% of the naltrexone C max  of an equal amount of immediate-release naltrexone hydrochloride; and   b) a naltrexone AUC last  that is about 80% and about 125% of the naltrexone AUC last  of an equal amount of immediate-release naltrexone hydrochloride.   
     
     
         14 . The method of  claim 11 , wherein said sustained-release formulation of naltrexone provides an in vivo plasma concentration profile of:
 a) a 6-beta naltrexol C max  that is less than about 80% of the 6-beta naltrexol C max  of an equal amount of immediate-release naltrexone hydrochloride; and   b) a 6-beta naltrexol AUC last  that is about 80% and about 125% of the 6-beta naltrexol AUC last  of an equal amount of immediate-release naltrexone hydrochloride.   
     
     
         15 . A method of treating overweight or obesity comprising orally administering daily about 16 mg to about 32 mg of naltrexone and about 360 mg of bupropion, or pharmaceutically acceptable salts thereof, to a person in need thereof, wherein the bupropion or pharmaceutically acceptable salt thereof is administered as a sustained-release formulation, wherein the naltrexone or pharmaceutically acceptable salt thereof is administered as a sustained-release formulation, and wherein said sustained-release formulation of naltrexone has an in vitro naltrexone dissolution profile in a dissolution test of USP Apparatus 2 Paddle Method at 100 rpm in a dissolution medium of water at 37° C. of:
 a) about 67% to about 80% of naltrexone released in 1 hour; and 
 b) about 85% to about 96% of naltrexone released in 2 hours; and 
 wherein about 8 mg or about 16 mg of said sustained-release formulation of naltrexone or a pharmaceutically acceptable salt thereof is administered twice daily, and about 180 mg of said sustained-release formulation of bupropion or a pharmaceutically acceptable salt thereof is administered twice daily. 
 
     
     
         16 . The method of  claim 15 , wherein said sustained-release naltrexone or pharmaceutically acceptable salt thereof and said sustained-release bupropion or pharmaceutically acceptable salt thereof are administered in a single oral unit dosage form. 
     
     
         17 . The method of  claim 15 , wherein said sustained-release formulation of naltrexone provides an in vivo plasma concentration profile of:
 a) a naltrexone C max  that is less than about 80% of the naltrexone C max  of an equal amount of immediate-release naltrexone hydrochloride; and   b) a naltrexone AUC last  that is about 80% and about 125% of the naltrexone AUC last  of an equal amount of immediate-release naltrexone hydrochloride.   
     
     
         18 . The method of  claim 15 , wherein said sustained-release formulation of naltrexone provides an in vivo plasma concentration profile of:
 a) a 6-beta naltrexol C max  that is less than about 80% of the 6-beta naltrexol C max  of an equal amount of immediate-release naltrexone hydrochloride; and   b) a 6-beta naltrexol AUC last  that is about 80% and about 125% of the 6-beta naltrexol AUC last  of an equal amount of immediate-release naltrexone hydrochloride.