Oxymorphone controlled release formulations

Abstract

The invention pertains to a method of relieving pain by administering a controlled release pharmaceutical tablet containing oxymorphone which produces a mean minimum blood plasma level 12 to 24 hours after dosing, as well as the tablet producing the sustained pain relief.

1 . A method for treating pain in a human subject in need of acute or chronic pain relief, comprising the steps of:
 (a) Providing a solid oral dosage form of a controlled release oxymorphone formulation with a release rate profile designed to provide an adequate blood plasma level over at least 12 hours to provide sustained pain relief over this same period comprising about 20 mg to about 40 mg oxymorphone or a pharmaceutically acceptable salt thereof wherein oxymorphone is the sole active ingredient; and   (b) administering the dosage form to the subject, wherein the oxymorphone C max  is at least about 50% higher when the dosage form is administered to the subject under fed as compared to fasted conditions.   
     
     
         2 . The method of  claim 1  wherein the dosage form comprises about 40 mg oxymorphone or a pharmaceutically acceptable salt thereof, and wherein the oxymorphone C max  is about 58% higher when the dosage form is administered to the subject under fed as compared to fasted conditions. 
     
     
         3 . The method of  claim 1  wherein the dosage form comprises about 20 mg oxymorphone or a pharmaceutically acceptable salt thereof. 
     
     
         4 . The method of  claim 1  wherein the dosage form comprises about 20 mg to about 40 mg oxymorphone hydrochloride. 
     
     
         5 . The method of  claim 1  wherein the difference in AUC (0-inf)  between fed and fasted conditions is less than about 20%. 
     
     
         6 . The method of  claim 1  wherein the difference in AUC (0-inf)  between fed and fasted conditions is about 18%. 
     
     
         7 . The method of  claim 1  wherein upon oral administration of the dosage form to the subject under fed or fasting conditions:
 (i) the dosage form provides detectable blood plasma levels of 6-OH oxymorphone and oxymorphone;   (ii) the blood plasma levels of 6-OH oxymorphone and oxymorphone peak within about 1 hour to about 8 hours after administration; and   (iii) the blood plasma levels of 6-OH oxymorphone and oxymorphone exhibit a ratio of AUC (0-inf)  of blood plasma level versus time for 6-OH oxymorphone compared to oxymorphone in a range of about 0.5 to about 1.5.   
     
     
         8 . A method for treating pain in a human subject in need of acute or chronic pain relief, comprising the steps of:
 (a) Providing a solid oral dosage form comprising about 5 mg to about 80 mg oxymorphone or a pharmaceutically acceptable salt thereof in a controlled release delivery system with a release rate profile designed to provide an adequate blood plasma level over at least 12 hours to provide sustained pain relief over this same period, the system comprising a filler and a hydrophilic material, wherein oxymorphone is the sole active ingredient; and   (b) administering the dosage form to the subject, wherein the oxymorphone C max  is at least about 50% higher when the dosage form is administered to the subject under fed versus fasted conditions.   
     
     
         9 . The method of  claim 8  wherein the oxymorphone C max  is at least about 58% higher when the dosage form is administered to the subject under fed as compared to fasted conditions. 
     
     
         10 . The method of  claim 8  wherein the difference in AUC (0-inf)  between fed and fasted conditions is less than about 20%. 
     
     
         11 . The method of  claim 8  wherein the difference in AUC (0-inf)  between fed and fasted conditions is about 18%. 
     
     
         12 . The method of  claim 8  wherein upon oral administration of the dosage form to the subject under fed or fasting conditions:
 (i) the dosage form provides detectable blood plasma levels of 6-OH oxymorphone and oxymorphone;   (ii) the blood plasma levels of 6-OH oxymorphone and oxymorphone peak within about 1 hour to about 8 hours after administration; and   (iii) the blood plasma levels of 6-OH oxymorphone and oxymorphone exhibit a ratio of AUC (0-inf)  of blood plasma level versus time for 6-OH oxymorphone compared to oxymorphone in a range of about 0.5 to about 1.5.   
     
     
         13 . The method of  claim 8  wherein the hydrophilic material comprises at least one of:
 a. a heteropolysaccharide; or   b. a heteropolysaccharide and a cross-linking agent capable of cross-linking the heteropolysaccharide; or   c. a mixture (b) and a cationic cross-linking agent.   
     
     
         14 . The method of  claim 13  wherein the heteropolysaccharide is a water soluble polysaccharide containing two or more kinds of sugar units and having a branched or helical configuration. 
     
     
         15 . The method of  claim 13  wherein the heteropolysaccharide is selected from the group consisting of xanthan gum, deacylated xanthan gum, carboxymethyl ether xanthan gum, propylene glycol ester xanthan gum and mixtures thereof. 
     
     
         16 . The method of  claim 13  wherein the cross-linking agent is a homopolysaccharide gum. 
     
     
         17 . The method of  claim 13  wherein the homopolysaccharide gum is locust bean gum. 
     
     
         18 . The method of  claim 13  wherein the filler is selected from the group consisting of sucrose, dextrose, lactose, microcrystalline cellulose, fructose, xylitol, sorbitol, and mixtures thereof. 
     
     
         19 . An analgesically effective controlled release pharmaceutical composition for oral delivery, comprising:
 a. a controlled release delivery system with a release rate profile designed to provide an adequate blood plasma level over at least 12 hours to provide sustained pain relief over this same period; and   b. about 5 mg to about 80 mg of oxymorphone or a pharmaceutically acceptable salt of oxymorphone, wherein oxymorphone is the sole active ingredient, wherein upon oral administration of a single dose of the composition to a human subject, the oxymorphone C max  is at least about 50% higher when the dose is administered to the subject under fed as compared to fasted conditions.   
     
     
         20 . The dosage form of  claim 19  wherein upon oral administration thereof the oxymorphone AUC (0-inf)  is no more than 20% higher when the dosage form is administered to the subject under fed as compared to fasted conditions.