Oral dosage forms for oxygen-containing active agents and oxyl-containing polymer

Abstract

The disclosed invention is drawn to pharmaceutical tablets that provide delivery of active agents having at least three oxygen-containing groups, as well as a second active ingredient. Non-limiting examples of three oxygen-containing group active agents include guaifenesin, codeine, hydrocodone, and their pharmaceutically acceptable salts. In one embodiment, a pharmaceutical tablet for oral administration once every 12 hours is provided. The tablet includes a first active agent that is a tri-oxy active agent, a second active agent, and a release rate controlling non-ionic oxyl-containing hydrophilic polymer. The total oxyl content of the hydrophilic polymer in the tablet is about 4×10 −4 moles to about 2.0×10 −3 moles.

1 .- 20 . (canceled) 
     
     
         21 . A solid matrix tablet pharmaceutical composition consisting essentially of a monolithic extended release matrix having:
 30 mg of codeine phosphate and 600 mg of guaifenesin in homogenous admixture in the matrix;   60 to 150 mg of release rate controlling non-ionic oxyl-containing hydrophilic polymer;   and one or more pharmaceutical processing aids.   
     
     
         22 . The pharmaceutical composition of  claim 21  wherein said release rate controlling non-ionic oxyl-containing hydrophilic polymer comprises hydroxypropyl methylcellulose. 
     
     
         23 . The pharmaceutical composition of  claim 21  wherein when placed in a USP Type II (paddle) Dissolution Apparatus set at 50 rpm in about 900 mL of 0.1 N hydrochloric acid solution in water at about 37° C. the composition releases 25% of the codeine phosphate and guaifenesin in said composition by a time point of from 0.25 hours to 1.0 hours, 50% of the codeine phosphate and guaifenesin in said composition by at a time point of from 1.5 hours to 4.0 hours or 75% of the codeine phosphate and guaifenesin in said composition by a time point of from 4.0 hours to 8.0 hours 
     
     
         24 . An extended release monolithic solid matrix tablet pharmaceutical composition comprising 30 mg of codeine phosphate; 600 mg guaifenesin; and 60 mg to 150 mg release rate controlling non-ionic oxyl-containing hydrophilic polymer wherein the codeine phosphate and guaifenesin are present as a homogenous admixture within the matrix. 
     
     
         25 . The pharmaceutical composition of  claim 24  having from 60 mg to 125 mg of a release rate controlling non-ionic oxyl-containing hydrophilic polymer which is hydroxypropyl methylcellulose. 
     
     
         26 . The pharmaceutical composition of  claim 24  said composition releasing 25% of said codeine and guaifenesin by a time point of from of from 0.25 hours and 1.0 hours, 50% of said codeine and guaifenesin by a time point of from 1.5 hours and 4.0 hours or 75% of said codeine and guaifenesin by a time point of from 4.0 hours and 8.0 hours as determined using a USP Type II (paddle) Dissolution Apparatus set at 50 rpm in about 900 mL of 0.1 N hydrochloric acid solution in water at about 37° C. 
     
     
         27 . The pharmaceutical composition of  claim 24  which when placed in a USP Type II (paddle) Dissolution Apparatus at 50 rpm in 900 mL of 0.1 N hydrochloric acid solution in water at 37° C. releases about 50% of the codeine phosphate by a time point of from 1.5 hours to 3 hours. 
     
     
         28 . A single layer solid matrix tablet pharmaceutical composition comprising: codeine, or a pharmaceutically acceptable salt thereof, and guaifenesin in homogenous admixture in said single layer solid matrix; and 60 mg to 150 mg of a release rate controlling non-ionic oxyl containing polymer, said composition being substantially free of ionic polymer wherein when placed in a USP Type II Dissolution Apparatus at 50 rpm in 900 mL of 0.1 N hydrochloric acid solution in water at 37° C. the tablet releases about 50% of the codeine phosphate or pharmaceutically acceptable salt thereof by a time point of from 1.5 hours to 3 hours. 
     
     
         29 . The pharmaceutical composition of  claim 28  which when placed in a USP Type II Dissolution Apparatus at 50 rpm in 900 mL of 0.1 N hydrochloric acid solution in water at 37° C. provides a ratio of an amount of codeine or pharmaceutically acceptable salt thereof released to an amount of guaifenesin released at a single time point between 1 hour and 4 hours of from about 0.8:1 to about 1.2:1 
     
     
         30 . The pharmaceutical composition of  claim 28  wherein the release rate controlling non-ionic oxyl containing polymer is hydroxypropyl methylcellulose. 
     
     
         31 . The pharmaceutical composition of  claim 28  wherein said release rate controlling non-ionic oxyl containing polymer comprises hydroxypropyl methylcellulose which is present in an amount of from 60 mg to 125 mg. 
     
     
         32 . The pharmaceutical composition of  claim 28  wherein said codeine or pharmaceutically acceptable salt thereof is 30 mg of codeine phosphate. 
     
     
         33 . A single layer tablet consisting of:
 (a) a first active agent which is codeine or a pharmaceutically acceptable salt thereof;   (b) a second active agent which is guaifenesin;   (c) a release rate controlling non-ionic oxyl-containing hydrophilic polymer; and   (d) one or more pharmaceutical processing aids,   wherein the tablet releases about 50% of the codeine or pharmaceutically acceptable salt by a time point of from 1.5 hours to 3 hours when said single layer tablet is placed in a USP Type II Dissolution Apparatus at 50 rpm in 900 mL of 0.1 N hydrochloric acid solution in water at 37° C. and said first active agent, said second active agent and said release rate controlling non-ionic oxyl-containing hydrophilic polymer are present in amounts sufficient to provide therapeutically effective amounts of said first active agent and said second active agent sufficient for dosing to a human subject once every 12 hours wherein said first active agent and said second active agent are in a homogenous admixture within said single layer tablet.   
     
     
         34 . The single layer tablet of  claim 33  said first active agent is 30 mg of codeine phosphate. 
     
     
         35 . The single layer tablet of  claim 33  wherein said second active agent is 600 mg of guaifenesin. 
     
     
         36 . The single layer tablet of  claim 33  wherein said release rate controlling non-ionic oxyl-containing hydrophilic polymer is present in an amount of from 60 mg to 150 mg. 
     
     
         37 . The single layer tablet of  claim 34  wherein said the release rate controlling non-ionic oxyl-containing hydrophilic polymer comprises hydroxypropyl methylcellulose which is present in an amount of from 60 mg to 125 mg. 
     
     
         38 . The single layer tablet of  claim 34  which is substantially free of ionic polymer. 
     
     
         39 . The single layer tablet of  claim 34  wherein the hydroxypropyl methylcellulose having an average apparent viscosity of about 3000 cP to about 15000 cP when determined in a 2% solution in water at 20° C. 
     
     
         40 . The single layer tablet of  claim 34  that has no food effect when administered to a human subject. 
     
     
         41 . The single layer tablet of  claim 34  which is resistant to alcohol associated dose dumping.