Pharmaceutical resinate compositions and methods of making and using thereof

Abstract

Disclosed herein are pharmaceutical compositions having a mixture of at least one active agent, an ion exchange resin, a binder, and a matrix material such that the composition, when administered to a patient in need thereof, provides the patient with a therapeutic effect for at least about 8 hours and related methods. Also disclosed herein are pharmaceutical compositions having a mixture of a drug susceptible to abuse, a non-opioid analgesic and an ion exchange resin, the composition further including at least one gelling agent and related methods.

1 - 68 . (canceled) 
     
     
         69 . A method of treating pain in a subject, comprising; administering to the subject, a pharmaceutical composition, comprising:
 a mixture comprising:
 at least one active agent comprising an opioid agonist, 
 an ion exchange resin; 
 a binder; and 
 a matrix material, 
   wherein the composition, when administered to a patient in need thereof, provides the patient with a therapeutic effect for at least about 8 hours.   
     
     
         70 - 143 . (canceled) 
     
     
         144 . The pharmaceutical composition of claim  6  wherein the opioid agonist is selected from the group consisting of oxycodone, oxycodone hydrochloride, oxymorphone, hydrocodone, hydrocodone bitartrate, hydromorphone, hydromorphone hydrochloride, morphine, codeine, tramadol, tapentadol, fentanyl, and pharmaceutically acceptable salts, hydrates and solvates thereof, and mixtures thereof. 
     
     
         145 . The pharmaceutical composition of claim  6 Error! Reference source not found., further comprising at least one second active agent. 
     
     
         146 . The pharmaceutical composition of claim  45  Error! Reference source not found.45, wherein the at least one second active agent comprises a non-opioid analgesic. 
     
     
         147 . The pharmaceutical composition of  claim 146 , wherein the non-opioid analgesic is chosen from non-steroidal anti-inflammatory agents and acetaminophen. 
     
     
         148 . The pharmaceutical composition of  claim 145 , wherein the at least one second active agent comprises an antagonist to the opioid agonist. 
     
     
         149 . The pharmaceutical composition of  claim 148 , wherein the antagonist is selected from the group consisting of naltrexone, naltrexone hydrochloride, naloxone, naloxone hydrochloride, nalmefene, cyclazacine, levallorphan, buprenorphine, pharmaceutically acceptable salts, hydrates and solvates thereof, and mixtures thereof. 
     
     
         150 . The pharmaceutical composition of  claim 69 , wherein the ion exchange resin comprises at least one material selected from the group consisting of (i) sulfonated copolymer of styrene and divinylbenzene, (ii) methacrylic acid-divinylbenzene copolymers, and (iii) polystyrene resins having amine and/or ammonium side groups. 
     
     
         151 . The pharmaceutical composition of  claim 69 , wherein the weight ratio of the ion exchange resin to the at least one active agent is from about 1:1 to about 10:1. 
     
     
         152 . The pharmaceutical composition of  claim 69 , wherein the binder is selected from the group consisting of a low molecular weight hydroxypropylmethylcellulose, a low molecular weight hydroxypropylcellulose, a low molecular weight hydroxyethylcellulose, polyethylene glycol, an acrylic polymer, an acrylic copolymer, a graft copolymer of polyvinyl alcohol and polyethylene glycol, a polyvinyl alcohol, alginic acid, sodium alginate, starch, pregelatinized starch, sucrose, guar gum, derivatives thereof and combinations thereof. 
     
     
         153 . The pharmaceutical composition of  claim 69 , wherein the binder comprises a cellulosic polymer comprising a molecular weight of about 100 Da to less than 1,000,000 Da. 
     
     
         154 . The pharmaceutical composition of  claim 69 , wherein the binder comprises hydroxypropylmethylcellulose comprising a molecular weight of about 100 Da to less than 1,000,000 Da. 
     
     
         155 . The pharmaceutical composition of  claim 69 , wherein the mixture comprises granules, each granule comprising the active agent, the ion exchange resin and the binder. 
     
     
         156 . The pharmaceutical composition of  claim 69 , wherein the at least one active agent and the ion exchange resin are in the form of a complex. 
     
     
         157 . The pharmaceutical composition of  claim 69  further comprising at least one pharmaceutically acceptable excipient. 
     
     
         158 . The pharmaceutical composition of  claim 157 , wherein the at least one pharmaceutically acceptable excipient is selected from the group consisting plasticizers, colorants, lubricants, thermal lubricants, antioxidants, buffering agents, disintegrants, binding agents, diluents, glidants, anti-adherants, sweeteners, chelating agents, flavorants, surfactants, solubilizers, stabilizers, hydrophilic polymers, hydrophobic polymers, waxes, lipophilic materials, absorption enhancers, preservative, absorbent, cross-linking agents, bioadhesive polymers, pore formers, osmotic agents, polycarboxylic acids, and combinations thereof, and/or
 wherein the pharmaceutically acceptable excipient comprises a mixture of lactose monohydrate and microcrystalline cellulose.   
     
     
         159 . The pharmaceutical composition of  claim 69 , wherein the matrix material is selected from the group consisting of a high molecular weight hydroxypropylmethylcellulose, a high molecular weight polyethylene oxide, a high molecular weight hydroxyethylcellulose, a high molecular weight hydroxypropylcellulose, a high molecular weight methylcellulose, an alginate, a carbopol, a polymethacrylate, a wax, carnauba wax, beeswax, glycerine alginate, a polyglycolyzed glyceride and combinations thereof, or
 wherein the matrix material comprises a polymer having a molecular weight of about 500,000 Da to about 10,000,000 Da, or   wherein the matrix material comprises a hydroxypropyl methylcellulose having a molecular weight of about 1,000,000 Da to about 7,500,000 Da.   
     
     
         160 . The pharmaceutical composition of  claim 69 , wherein the composition releases about 10% to about 45% active agent after 1 hour, about 12.5% to about 55% (by weight) active agent after 2 hours, about 25% to about 65% (by weight) active agent after 4 hours, about 45% to about 85% (by weight) active agent after 6 hours and about 55% to about 95% (by weight) active agent after 8 hours, and optionally about 75% to 100% (by weight) active agent after 12 hours, when measured by in-vitro dissolution in a USP Apparatus 2 (paddle) at about 50 rpm in about 900 ml simulated gastric fluid at about 37° C., and/or
 wherein the composition releases about 10% or less of the at least one active agent within about 20 minutes as measured by in-vitro dissolution in a USP Apparatus 2 (paddle) at about 50 rpm in about 900 ml water at about 37° C., and/or 
 wherein the composition releases about 10% or less of the at least one active agent within about 20 minutes as measured by in-vitro dissolution in a USP Apparatus 2 (paddle) at about 50 rpm in about 900 ml 40% ethanol in water v/v at about 37° C. 
 
     
     
         161 . The pharmaceutical composition of  claim 69 , wherein recovery of the at least one active agent is less than about 20% based on a syringeability test whereby the composition is subject to dissolution in 10 ml of water with agitation at room temperature for about 2 min and the resultant solution is aspirated with a 21-gauge needle, and/or
 wherein recovery of the at least one active agent is less than about 20% based on a syringeability test whereby the composition is subject to dissolution in 10 ml of water with agitation at 95° C. for about 2 min and the resultant solution is aspirated with a 21-gauge needle.   
     
     
         162 . A method of treating pain in a subject, comprising:
 administering to the subject, a pharmaceutical composition, comprising:   a mixture comprising:
 at least one active agent comprising an opioid agonist; 
 an ion exchange resin; 
 a first hydroxypropylmethylcellulose having a first molecular weight; and 
 a second hydroxypropylmethylcellulose having a second molecular weight, 
   wherein the composition, when administered to a patient in need thereof, provides the patient with a therapeutic effect for at least about 8 hours.