Opioid-Containing Oral Pharmaceutical Compositions and Methods

Abstract

The present invention provides sustained-release oral pharmaceutical compositions and methods of use. The sustained-release oral pharmaceutical compositions include an opioid (including salts thereof) and a salt of a non-steroidal anti-inflammatory drug (NSAID).

1 . (canceled) 
     
     
         2 . A method of preventing, alleviating, or ameliorating the level of pain in a subject, the method comprising administering to a subject a sustained-release oral pharmaceutical composition comprising within a single dose:
 a hydrophilic matrix;   a therapeutically effective amount of an opioid or salt thereof; and   a salt of a non-steroidal anti-inflammatory drug (NSAID),   wherein the opioid and the salt of an NSAID are within the hydrophilic matrix; and
 wherein the opioid or salt thereof is released as a result of dissolution of the hydrophilic matrix. 
   
     
     
         3 . The method of  claim 2 , wherein the composition exhibits a release profile with respect to the opioid comprising a substantial portion that is representative of zero-order release kinetics under in vitro conditions. 
     
     
         4 . The method of  claim 2 , wherein the composition further comprises one or more pharmaceutically acceptable anionic surfactants, wherein the one or more surfactants are in the hydrophilic matrix in an amount effective to modify the rate of release of the opioid from the hydrophilic matrix. 
     
     
         5 . The method of  claim 4 , wherein the one or more anionic surfactants are selected from the group consisting of sodium lauryl sulfate, docusate sodium, docusate calcium, and combinations thereof. 
     
     
         6 . The method of  claim 2 , wherein the opioid comprises a tertiary amine. 
     
     
         7 . The method of  claim 2 , wherein the opioid is selected from the group consisting of morphine, codeine, hydromorphone, hydrocodone, oxycodone, oxymorphone, desomorphine, diacetylmorphine, buprenorphine, dihydrocodeine, nicomorphine, benzylmorphine, fentanyl, methadone, tramadol, propoxyphene, levorphanol, and meperidine. 
     
     
         8 . The method of  claim 2 , wherein the opioid is selected from the group consisting of hydrocodone, tramadol, a salt of hydrocodone, or a salt of tramadol. 
     
     
         9 . The method of  claim 2 , wherein the NSAID salt is selected from the group consisting of a salt of naproxen, a salt of diclofenac, and a salt of ibuprofen. 
     
     
         10 . The method of  claim 2 , wherein the NSAID salt is present in an amount effective to provide zero-order release kinetics of the opioid from the hydrophilic matrix under in vitro conditions. 
     
     
         11 . The method of  claim 2 , wherein the hydrophilic matrix comprises a methylcellulose, a hydroxypropyl methylcellulose, and combinations thereof. 
     
     
         12 . The method of  claim 2 , wherein the hydrophilic matrix comprises a hydroxypropyl methylcellulose. 
     
     
         13 . The method of  claim 2  wherein the single dosage form is a tablet form. 
     
     
         14 . A method of suppressing cough in a subject, the method comprising administering a sustained-release oral pharmaceutical composition comprising within a single dose:
 a hydrophilic matrix;   a therapeutically effective amount of an opioid or salt thereof; and   a salt of a non-steroidal anti-inflammatory drug (NSAID),   wherein the opioid and the salt of an NSAID are within the hydrophilic matrix; and
 wherein the opioid or salt thereof is released as a result of dissolution of the hydrophilic matrix. 
   
     
     
         15 . The method of  claim 14 , wherein the composition exhibits a release profile with respect to the opioid comprising a substantial portion that is representative of zero-order release kinetics under in vitro conditions. 
     
     
         16 . The method of  claim 14 , wherein the composition further comprises one or more pharmaceutically acceptable anionic surfactants, wherein the one or more surfactants are in the hydrophilic matrix. 
     
     
         17 . The method of  claim 16 , wherein the anionic surfactant is present in the hydrophilic matrix in an amount effective to modify the rate of release of the opioid from the hydrophilic matrix. 
     
     
         18 . The method of  claim 14 , wherein the opioid is selected from the group consisting of morphine, codeine, hydromorphone, hydrocodone, oxycodone, oxymorphone, desomorphine, diacetylmorphine, buprenorphine, dihydrocodeine, nicomorphine, benzylmorphine, fentanyl, methadone, tramadol, propoxyphene, levorphanol, and meperidine. 
     
     
         19 . The method of  claim 14 , wherein the opioid is a salt comprising a hydrochloride, a bitartrate, an acetate, a naphthylate, a tosylate, a mesylate, a besylate, a succinate, a palmitate, a stearate, an oleate, a pamoate, a laurate, a valerate, a hydrobromide, a sulfate, a methane sulfonate, a tartrate, a citrate, or a maleate. 
     
     
         20 . The method of  claim 14 , wherein the NSAID salt is selected from the group consisting of a salt of naproxen, a salt of diclofenac, and a salt of ibuprofen. 
     
     
         21 . The method of  claim 14 , wherein the NSAID salt is present in an amount effective to provide zero-order release kinetics of the opioid from the hydrophilic matrix under in vitro conditions.