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) morphine 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 morphine 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 750 ng to about 750 mg of morphine or a pharmaceutically acceptable salt thereof. 
     
     
         47 . The sustained release oral dosage form of  claim 41 , comprising from about 2.5 to about 800 mg of morphine or a pharmaceutically acceptable salt thereof. 
     
     
         48 . The sustained release oral dosage form of  claim 46 , wherein the morphine or a pharmaceutically acceptable salt thereof comprises morphine sulfate. 
     
     
         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 morphine or pharmaceutically acceptable salt thereof comprises morphine sulfate. 
     
     
         64 . The sustained release oral dosage form of  claim 63 , comprising from about 2.5 mg to about 800 mg morphine sulfate. 
     
     
         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 morphine 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 morphine 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) morphine sulfate;   
       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) morphine sulfate;   
       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 and wherein the ratio of gelling agent to morphine sulfate is from about 1:1 to about 40:1.