Pharmaceutical Formulation Containing Gelling Agent

Abstract

Disclosed in certain embodiments is a controlled release oral dosage form comprising a therapeutically effective amount of a drug susceptible to abuse together with one or more pharmaceutically acceptable excipients; the dosage form further including a gelling agent in an effective amount to impart a viscosity unsuitable for administration selected from the group consisting of parenteral and nasal administration to a solubilized mixture formed when the dosage form is crushed and mixed with from about 0.5 to about 10 ml of an aqueous liquid; the dosage form providing a therapeutic effect for at least about 12 hours when orally administered to a human patient.

1 - 40 . (canceled) 
     
     
         41 . A controlled release oral dosage form comprising:
 a mixture of (i) from about 10 mg to about 160 mg of a pharmaceutically acceptable salt of oxycodone; and   (ii) a gelling agent comprising polyethylene oxide, the gelling agent in an effective amount to impart a viscosity unsuitable for parenteral administration when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid;   the dosage form having a ratio of gelling agent to oxycodone or pharmaceutically acceptable salt thereof from about 40:1 to about 1:40;   the dosage form providing a therapeutic effect for at least about 12 hours when orally administered to a human patient and a mean minimum plasma concentration of oxycodone from about 3 to about 120 ng/ml from about 10 to about 14 hours after administration every 12 hours after repeated dosing through steady state conditions.   
     
     
         42 . The controlled release oral dosage form of  claim 41 , wherein the gelling agent is in an effective amount to impart a viscosity of at least about 10 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid. 
     
     
         43 . The controlled release oral dosage form of  claim 41 , wherein the gelling agent is in an effective amount to impart a viscosity of at least about 60 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid. 
     
     
         44 . The controlled release oral dosage form of  claim 41 , wherein the gelling agent is in an effective amount to impart a viscosity of at least about 120 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid. 
     
     
         45 . The controlled release oral dosage form of  claim 41 , wherein the gelling agent is in an effective amount to impart a viscosity of at least about 2,000 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid. 
     
     
         46 . The controlled release oral dosage form of  claim 41 , wherein the gelling agent is in an effective amount to impart a viscosity from about 120 cP to about 5,000 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid. 
     
     
         47 . The controlled release oral dosage form of  claim 46 , providing a mean maximum plasma concentration of oxycodone from about 6 to about 240 ng/ml from a mean of about 2 to about 4.5 hours after administration. 
     
     
         48 . The controlled release oral dosage form of  claim 47 , comprising (i) from about 10 to about 40 mg oxycodone hydrochloride, the dosage form providing a mean maximum plasma concentration of oxycodone from about 6 to about 60 ng/ml from a mean of about 2 to about 4.5 hours after administration or (ii) from about 40 mg to about 160 mg oxycodone hydrochloride, the dosage form providing a mean maximum plasma concentration of oxycodone from about 60 to about 240 ng/ml from a mean of about 2 to about 4.5 hours after administration. 
     
     
         49 . The controlled release oral dosage form of  claim 41 , wherein the imparted viscosity makes the tampered dosage form difficult to pull into an insulin syringe. 
     
     
         50 . The controlled release oral dosage form of  claim 41 , wherein the imparted viscosity makes the tampered dosage form difficult to pull into an insulin syringe as compared to the same dosage form having an inert pharmaceutically acceptable excipient in place of the gelling agent. 
     
     
         51 . The controlled release oral dosage form of  claim 46 , wherein the imparted viscosity makes the tampered dosage form difficult to pull into an insulin syringe as compared to the same dosage form having an inert pharmaceutically acceptable excipient in place of the gelling agent. 
     
     
         52 . The controlled release oral dosage form of  claim 41 , wherein a tampered dosage form cannot be filled into an insulin syringe without picking up pockets of air. 
     
     
         53 . The controlled release oral dosage form of  claim 41 , wherein a tampered dosage form has a milk like color. 
     
     
         54 . The controlled release oral dosage form of  claim 41 , wherein the aqueous liquid is water. 
     
     
         55 . The controlled release oral dosage form of  claim 41 , wherein the viscosity is imparted when the dosage form is subjected to tampering by dissolution in about 1 to about 3 ml of aqueous liquid. 
     
     
         56 . The controlled release oral dosage form of  claim 43 , wherein the viscosity is imparted when the dosage form is subjected to tampering by crushing and dissolution in the aqueous liquid. 
     
     
         57 . The controlled release oral dosage form of  claim 41 , wherein the viscosity is imparted when the dosage form is subjected to tampering by dissolution in the aqueous liquid at ambient temperature. 
     
     
         58 . The controlled release oral dosage form of  claim 41 , wherein the viscosity is imparted when the dosage form is subjected to tampering by dissolution in the aqueous liquid with heating greater than 45° C. 
     
     
         59 . The controlled release oral dosage form of  claim 53 , wherein the gelling agent is in an effective amount to impart a viscosity of at least about 10 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid. 
     
     
         60 . The controlled release oral dosage form of  claim 53 , wherein the gelling agent is in an effective amount to impart a viscosity of at least about 60 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid. 
     
     
         61 . The controlled release oral dosage form of  claim 53 , wherein the gelling agent is in an effective amount to impart a viscosity of at least about 120 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid. 
     
     
         62 . The controlled release oral dosage form of  claim 53 , wherein the gelling agent is in an effective amount to impart a viscosity from about 120 cP to about 5,000 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid. 
     
     
         63 . The controlled release oral dosage form of  41 , wherein the gelling agent further comprises a cellulosic polymer. 
     
     
         64 . The controlled release oral dosage form of  claim 41 , comprising from about 10 mg to about 80 mg oxycodone hydrochloride. 
     
     
         65 . The controlled release dosage form of  claim 41 , wherein the polyethylene oxide has a weight average molecular weight from about 100,000 daltons to about 1,000,000 daltons. 
     
     
         66 . The controlled release dosage form of  claim 41 , wherein the polyethylene oxide has a weight average molecular weight from about 1,000,000 daltons to about 10,000,000 daltons. 
     
     
         67 . The controlled release dosage form of  claim 41 , wherein the ratio of gelling agent to oxycodone or pharmaceutically acceptable salt thereof is from about 1:1 to about 30:1. 
     
     
         68 . The controlled release dosage form of  claim 41 , wherein the ratio of gelling agent to oxycodone or pharmaceutically acceptable salt thereof is from about 2:1 to about 15:1. 
     
     
         69 . A controlled release oral dosage form comprising:
 a mixture of (i) from about 10 mg to about 160 mg oxycodone or a pharmaceutically acceptable salt thereof; and   (ii) a gelling agent comprising polyethylene oxide, the gelling agent in an effective amount to impart a viscosity of at least 10 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid;   the dosage form having a ratio of gelling agent to oxycodone or pharmaceutically acceptable salt thereof from about 30:1 to about 1:30;   the dosage form providing a therapeutic effect for at least about 12 hours when orally administered to a human patient and a mean minimum plasma concentration of oxycodone from about 3 to about 120 ng/ml from about 10 to about 14 hours after administration every 12 hours after repeated dosing through steady state conditions.   
     
     
         70 . The controlled release oral dosage form of  claim 69 , wherein the gelling agent is in an effective amount to impart a viscosity of at least about 60 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid.