Method of treating pain by administering 24 hour oral opioid formulations exhibiting rapid rate of initial rise of plasma drug level

Abstract

Patients are treated with 24-hour oral sustained release opioid formulations which, upon administration, provide an initially rapid opioid absorption such that the minimum effective analgesic concentration of the opioid is more quickly achieved. These sustained release opioid formulations include an effective amount of at least one retardant material to cause said opioid analgesic to be released at a such a rate as to provide an analgesic effect after oral administration to a human patient for at least about 24 hours, and are characterized by providing an absorption half-life from 1 to about 8 hours. A method of titrating a human patient utilizing these sustained release opioid formulations is also disclosed.

1 - 26 . (canceled)  
   
   
       27 . A formulation comprising: 
 (a) an opioid analgesic selected from the group consisting of oxymorphone and oxymorphone salts; and    (b) at least one retardant material causing the opioid analgesic to be released at a rate to provide an analgesic effect for at least about 12 hours after oral administration to a patient,    wherein said formulation, when administered to the patient, provides an initially rapid rate of rise in plasma concentration of the opioid analgesic and an absorption half-life from about 1 to about 8 hours.    
   
   
       28 . The formulation according to  claim 27 , wherein the retardant material is selected from the group consisting of: acrylic polymers, alkyl cellulose, shellac, zein, hydrogenated vegetable oil, hydrogenated castor oil, and mixtures of any two or more of the foregoing.  
   
   
       29 . The formula according to  claim 27 , which formulation comprises a plurality of substrates each having a diameter from about 0.5 to about 2 mm.  
   
   
       30 . The formulation according to  claim 29 , wherein the retardant material is coated on the surface of said substrates.  
   
   
       31 . The formulation according to  claim 29 , wherein said substrates comprise: (i) inert beads coated with the opioid analgesic, and (ii) an outer coating comprising the retardant material and imparting sustained release properties to the formulation.  
   
   
       32 . The formulation according to  claim 29 , wherein the substrates comprise matrices of a substantially uniform mixture, said mixture comprising the opioid analgesic and the retardant material.  
   
   
       33 . The formulation according to  claim 27 , wherein a portion of the dose of the opioid analgesic is included in an immediate release form.  
   
   
       34 . The formulation according to  claim 27 , in which the formulation is a tablet.  
   
   
       35 . The formulation according to  claim 34  further comprising at least one diluent.  
   
   
       36 . The formulation according to  claim 34  further comprising at least one lubricant.  
   
   
       37 . The formulation according to  claim 34  further comprising at least one binder.  
   
   
       38 . A formulation comprising: 
 (a) as a sole active ingredient, an opioid analgesic selected from the group consisting of oxymorphone and oxymorphone salts; and    (b) at least one retardant material causing the opioid analgesic to be released at a rate to provide an analgesic effect for at least about 12 hours after oral administration to a patient,    wherein said formulation, when administered to the patient, provides an initially rapid rate of rise in plasma concentration of the opioid analgesic and an absorption half-life from about 1 to about 8 hours.    
   
   
       39 . The formulation according to  claim 38 , wherein the retardant material is selected from the group consisting of: acrylic polymers, alkyl cellulose, shellac, zein, hydrogenated vegetable oil, hydrogenated castor oil, and mixtures of any two or more of the foregoing.  
   
   
       40 . The formulation according to  claim 38 , which formulation comprises a plurality of substrates, each having a diameter from about 0.5 to about 2 mm.  
   
   
       41 . The formulation according to  claim 40 , wherein the retardant material is coated on the surface of said substrate.  
   
   
       42 . The formulation according to  claim 40 , wherein said substrates comprise: (i) inert beads coated with the opioid analgesic, and (ii) an outer coating comprising the retardant material and imparting sustained release properties to the formulation.  
   
   
       43 . The formulation according to  claim 40 , wherein the substrates comprise matrices of a substantially uniform mixture, said mixture comprising the opioid analgesic and the retardant material.  
   
   
       44 . The formulation according to  claim 38  wherein a portion of the dose of the opioid analgesic is included in an immediate release form.  
   
   
       45 . The formulation according to  claim 38  in which the formulation is a tablet.  
   
   
       46 . The formulation according to  claim 45  further comprising at least one diluent.  
   
   
       47 . The formulation according to  claim 45  further comprising at least one lubricant.  
   
   
       48 . The formulation according to  claim 45  further comprising at least one binder.  
   
   
       49 . A method of treating a patient for pain, which method comprises orally administering to the patient a formulation which comprises: 
 (a) an opioid analgesic selected from the group consisting of oxymorphone and oxymorphone salts; and    (b) at least one retardant material causing the opioid analgesic to be released at a rate to provide an analgesic effect for at least about 12 hours after oral administration to a patient,    wherein said formulation, when administered to the patient, provides an initially rapid rate of rise in plasma concentration of the opioid analgesic and an absorption half-life from about 1 to about 8 hours.    
   
   
       50 . A method of treating a patient for pain, which method comprises orally administering to the patient a formulation which comprises: 
 (a) as a sole active ingredient, an opioid analgesic selected from the group consisting of oxymorphone and oxymorphone salts; and    (b) at least one retardant material causing the opioid analgesic to be released at a rate to provide an analgesic effect for at least about 12 hours after oral administration to a patient,    wherein said formulation, when administered to the patient, provides an initially rapid rate of rise in plasma concentration of the opioid analgesic and an absorption half-life from about 1 to about 8 hours.    
   
   
       51 . A method for preparing a formulation, 
 wherein said formulation comprises:    (a) an opioid analgesic selected from the group consisting of oxymorphone and oxymorphone salts; and    (b) at least one retardant material causing the opioid analgesic to be released at a rate to provide an analgesic effect for at least about 12 hours after oral administration to a patient,    said method being characterized in that the formulation is prepared to provide an initially rapid rise in plasma concentration of the opioid analgesic and an absorption half-life of from about 1 to about 8 hours.    
   
   
       52 . The method of  claim 51 , wherein the formulation is prepared to provide an absorption half-life of from about 1 to about 6 hours.  
   
   
       53 . The method of  claim 52 , wherein the formulation is prepared to provide an absorption half-life of from about 1 to about 3 hours.