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 sustained release abuse deterrent dosage form comprising:
 i) a core matrix comprising a blended mixture of   (a) a gelling agent comprising PEO having a molecular weight of from about 100,000 daltons to about 10,000,000 daltons;   (b) magnesium stearate; and   (c) oxycodone or a pharmaceutically acceptable salt thereof;   
       wherein the core matrix is heated to melt at least a portion of the PEO included in the core matrix during preparation of the dosage form; and
 ii) a coating applied onto the core matrix, the coating comprising a material selected from the group consisting of PEG, hydroxypropylmethylcellulose, polyvinyl alcohol and a mixture thereof; 
 wherein the dosage form provides sustained release of the oxycodone or pharmaceutically acceptable salt thereof. 
 
     
     
         42 . The sustained release dosage form of  claim 41 , providing a therapeutic effect for at least about 12 hours when orally administered to a human patient. 
     
     
         43 . The sustained 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. 
     
     
         44 . The sustained 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. 
     
     
         45 . The sustained 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. 
     
     
         46 . The sustained release oral dosage form of  claim 41 , comprising from about 10 mg to about 160 mg oxycodone hydrochloride, the dosage form providing 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. 
     
     
         47 . The sustained 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 sustained 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 sustained release oral dosage form of  claim 41 , wherein the gelling agent imparts a viscosity that is difficult to pull into an insulin syringe when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid. 
     
     
         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 sustained release oral dosage form of  claim 43 , wherein the aqueous liquid is water. 
     
     
         55 . The sustained release oral dosage form of  claim 43 , 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 sustained 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 sustained release oral dosage form of  claim 43 , wherein the viscosity is imparted when the dosage form is subjected to tampering by dissolution in the aqueous liquid at ambient temperature. 
     
     
         58 . The sustained release oral dosage form of  claim 43 , 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 sustained release oral dosage form of  claim 41 , wherein the gelling agent further comprises a cellulosic polymer. 
     
     
         60 . The sustained release oral dosage form of  claim 59 , wherein the cellulosic polymer is a hydroxyalkylcellulose. 
     
     
         61 . The sustained release oral dosage form of  claim 41 , wherein the coating comprises polyvinyl alcohol. 
     
     
         62 . The sustained release oral dosage form of  claim 41 , wherein the coating comprises hydroxypropylmethylcellulose. 
     
     
         63 . The sustained release oral dosage form of  41 , wherein the oxycodone or pharmaceutically acceptable salt thereof comprises oxycodone hydrochloride. 
     
     
         64 . The sustained release oral dosage form of  claim 63 , comprising from about 10 mg to about 80 mg oxycodone hydrochloride. 
     
     
         65 . The sustained 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 sustained 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 sustained 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 40:1. 
     
     
         68 . The sustained 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 30:1. 
     
     
         69 . A sustained release abuse deterrent dosage form comprising:
 i) a core matrix comprising a blended mixture of   (a) a gelling agent comprising PEO having a molecular weight of from about 300,000 daltons to about 10,000,000 daltons and hydroxypropylmethylcellulose;   (b) magnesium stearate; and   (c) oxycodone hydrochloride;   
       wherein the core matrix is heated to melt at least a portion of the PEO included in the core matrix during preparation of the dosage form; and
 ii) a coating applied onto the core matrix, the coating comprising a material selected from the group consisting of PEG, hydroxypropylmethylcellulose, polyvinyl alcohol and a mixture thereof; 
 wherein the gelling agent is 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 and the dosage form provides a therapeutic effect for at least about 12 hours when orally administered to a human patient. 
 
     
     
         70 . A sustained release abuse deterrent dosage form comprising:
 i) a core matrix comprising a blended mixture of   (a) a gelling agent comprising PEO having a molecular weight of from about 300,000 daltons to about 10,000,000 daltons and hydroxypropylmethylcellulose;   (b) magnesium stearate; and   (c) oxycodone hydrochloride;   
       wherein the core matrix is heated to melt at least a portion of the PEO included in the core matrix during preparation of the dosage form; and
 ii) a coating applied onto the core matrix, the coatin comprising a material selected from the group consisting of PEG, hydroxypropylmethylcellulose, polyvinyl alcohol and a mixture thereof; 
 wherein the gelling agent is 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 and the dosage form provides a therapeutic effect for at least about 12 hours when orally administered to a human patient and a 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 and wherein the ratio of gelling agent to oxycodone hydrochloride is from about 1:1 to about 40:1.