Extended release compositions of opioid antagonists and phosphodiesterase 5 inhibitors

Abstract

Pharmaceutical compositions of one or more opioid antagonists or phosphodiesterase 5 (PDE5) inhibitors are disclosed.

1 . A pharmaceutical composition, comprising:
 76.8-86.8% of naltrexone;   3-6% of stearic acid   10-20% of a pharmaceutically acceptable vehicle, wherein the vehicle is selected from glyceryl monostearate (GMS), glyceryl behenate, and glyceryl palmitostearate; and   0.2% of ascorbic acid.   
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the amount of naltrexone in the composition is 200 mg to 2,000 mg. 
     
     
         3 . The pharmaceutical composition according to  claim 1  or  2 , wherein the vehicle is glyceryl monostearate (GMS). 
     
     
         4 . The pharmaceutical composition according to any one of  claims 1  to  3 , wherein the composition is formulated to erode in at least 90 days. 
     
     
         5 . The pharmaceutical composition according to any one of  claims 1  to  4 , wherein the composition further comprises <1% of one or more antioxidants independently selected from methyl paraben and salts thereof, propyl paraben and salts thereof, vitamin E, vitamin E TPGS, propyl gallate, sulfites, sodium benzoate, citric acid, cyclodextrins, peroxide scavengers, benzoic acid, ethylenediaminetetraacetic acid (EDTA) and salts thereof, chain terminators (e.g., thiols and phenols), butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), and combinations thereof. 
     
     
         6 . The pharmaceutical composition according to any one of  claims 1  to  5 , wherein the composition is formulated to deliver a therapeutically effective amount of the naltrexone over a period of time selected from the group consisting of 60 days, 80 days, 90 days, 100 days, 180 days, 6 months, 9 months, and 10 months. 
     
     
         7 . The pharmaceutical composition of  claim 6 , wherein the therapeutically effective amount is from 1 ng/mL to 2 ng/mL and the period of time is one day. 
     
     
         8 . A method of treating an addiction, wherein the addiction is selected from an opioid addiction, an alcohol addiction, and an amphetamine addiction, where in the method comprises administering a pharmaceutical composition according to any one of  claims 1  to  7  to a subject. 
     
     
         9 . The use of naltrexone for the manufacture of the medicament for a treatment of an addiction, wherein the medicament is the pharmaceutical composition according to any one of  claims 1  to  8 . 
     
     
         10 . The use of  claim 9 , wherein the addiction is selected from an opioid addiction, an alcohol addiction, and an amphetamine addiction. 
     
     
         11 . The pharmaceutical composition according to any one of  claims 1  to  7  for use in the treatment of an addiction. 
     
     
         12 . The use of  claim 11 , wherein the addiction is selected from an opioid addiction, an alcohol addiction, and an amphetamine addiction. 
     
     
         13 . A pharmaceutical composition, comprising:
 76.8-86.8% of tadalafil;   3-6% of stearic acid;   10-20% of a pharmaceutically acceptable vehicle, wherein the vehicle is selected from glyceryl monostearate (GMS), glyceryl behenate, and glyceryl palmitostearate; and   0.2% of ascorbic acid.   
     
     
         14 . The pharmaceutical composition of  claim 13 , wherein the composition further comprises ≤1% of one or more antioxidants independently selected from methyl paraben and salts thereof, propyl paraben and salts thereof, vitamin E, vitamin E TPGS, propyl gallate, sulfites, sodium benzoate, citric acid, cyclodextrins, peroxide scavengers, benzoic acid, ethylenediaminetetraacetic acid (EDTA) and salts thereof, chain terminators (e.g., thiols and phenols), butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), and combinations thereof. 
     
     
         15 . The pharmaceutical composition according to  claim 13  or  14 , wherein the amount of tadalafil in the composition is 25 mg to 2,000 mg. 
     
     
         16 . The pharmaceutical composition according to any one of  claims 13  to  15 , wherein the vehicle is glyceryl monostearate (GMS). 
     
     
         17 . The pharmaceutical composition according to any one of  claims 13  to  16 , wherein the composition is formulated to erode in at least 90 days. 
     
     
         18 . The pharmaceutical composition according to any one of  claims 13  to  17 , wherein the composition is formulated to deliver a therapeutically effective amount of tadalafil over a period of time. 
     
     
         19 . The pharmaceutical composition according to any one of  claims 13  to  18 , wherein the therapeutically effective amount is from 2 ng/mL to 5 ng/mL and the period of time is one day. 
     
     
         20 . A method of treating one or more of erectile dysfunction, benign prostatic hyperplasia, and pulmonary hypertension, the method comprising administering a pharmaceutical composition according to any one of  claims 13  to  19  to a subject. 
     
     
         21 . The use of tadalafil in the manufacture of the medicament for a treatment of one or more of erectile dysfunction, benign prostatic hyperplasia, and pulmonary hypertension, wherein the medicament is the pharmaceutical composition according to any one of  claims 13  to  19 . 
     
     
         22 . The pharmaceutical composition according to any one of  claims 13  to  19  for use in the treatment of one or more of erectile dysfunction, benign prostatic hyperplasia, and pulmonary hypertension.