Sustained release of guaifenesin

Abstract

The invention relates to a novel pharmaceutical sustained release formulation of guaifenesin. The formulation may comprise a hydrophilic polymer, preferably a hydroxypropyl methylcellulose, and a water-insoluble polymer, preferably an acrylic resin, in a ratio range of about one-to-one (1: 1) to about nine-to-one (9: 1), more preferably a range of about three-to-two (3:2) to about six-to-one (6: 1), and most preferably in a range of about two-to-one (2: 1) to about four-to-one (4: 1) by weight. This formulation capable of providing therapeutically effective bioavailability of guaifenesin for at least twelve hours after dosing in a human subject. The invention also relates to a modified release product which has two portions: a first portion having an immediate release formulation of guaifenesin and a second portion having a sustained release formulation of guaifenesin. The modified release product has a maximum guaifenesin serum concentration equivalent to that of an immediate release guaifenesin tablet, and is capable of providing therapeutically effective bioavailability of guaifenesin for at least twelve hours after dosing in a human subject.

1 . A drug product comprising 1200 mg of guaifenesin and having two portions,
 wherein a first portion comprises guaifenesin in an immediate release form, which releases guaifenesin in a human subject's stomach, and a second portion comprises guaifenesin in a sustained release form,   wherein from about 27% to about 41% of a total amount of guaifenesin absorbed into bloodstream is absorbed within 0.5 hour after administration under fasted conditions, and   wherein guaifenesin is absorbed into the bloodstream such that the drug product can be appropriately dosed once in a 12-hour period.   
     
     
         2 . The drug product according to  claim 1 , wherein from about 33% to about 41% of the total amount of guaifenesin absorbed into the bloodstream is absorbed within 0.5 hour after administration under fasted conditions. 
     
     
         3 . The drug product according to  claim 1 , wherein about 27% of the total amount of guaifenesin absorbed into the bloodstream is absorbed within 0.5 hour after administration under fasted conditions. 
     
     
         4 . The drug product according to  claim 1 , wherein about 33% of the total amount of guaifenesin absorbed into the bloodstream is absorbed within 0.5 hour after administration under fasted conditions. 
     
     
         5 . The drug product according to  claim 1 , wherein about 41% of the total amount of guaifenesin absorbed into the bloodstream is absorbed within 0.5 hour after administration under fasted conditions. 
     
     
         6 . The drug product according to  claim 1 , wherein the first and second portions are discrete. 
     
     
         7 . The drug product according to  claim 6 , which is in a form of a bi-layer tablet. 
     
     
         8 . A drug product comprising 1200 mg of guaifenesin and having two portions,
 wherein a first portion comprises guaifenesin in an immediate release form, which releases guaifenesin in a human subject's stomach, and a second portion comprises guaifenesin in a sustained release form,   wherein from about 39% to about 55% of a total amount of guaifenesin absorbed into bloodstream is absorbed within 1 hour after administration under fasted conditions, and   wherein guaifenesin is absorbed into the bloodstream such that the drug product can be appropriately dosed once in a 12-hour period.   
     
     
         9 . The drug product according to  claim 8 , wherein from about 46% to about 55% of the total amount of guaifenesin absorbed into the bloodstream is absorbed within 1 hour after administration under fasted conditions. 
     
     
         10 . The drug product according to  claim 8 , wherein about 39% of the total amount of guaifenesin absorbed into the bloodstream is absorbed within 1 hour after administration under fasted conditions. 
     
     
         11 . The drug product according to  claim 8 , wherein about 46% of the total amount of guaifenesin absorbed into the bloodstream is absorbed within 1 hour after administration under fasted conditions. 
     
     
         12 . The drug product according to  claim 8 , wherein about 55% of the total amount of guaifenesin absorbed into the bloodstream is absorbed within 1 hour after administration under fasted conditions. 
     
     
         13 . The drug product according to  claim 8 , wherein the first and second portions are discrete. 
     
     
         14 . The drug product according to  claim 13 , which is in a form of a bi-layer tablet. 
     
     
         15 . A drug product comprising 1200 mg of guaifenesin and having two portions,
 wherein a first portion comprises guaifenesin in an immediate release form, which releases guaifenesin in a human subject's stomach, and a second portion comprises guaifenesin in a sustained release form,   wherein from about 48% to about 62% of a total amount of guaifenesin absorbed into bloodstream is absorbed within 1.5 hours after administration under fasted conditions, and   wherein guaifenesin is absorbed into the bloodstream such that the drug product can be appropriately dosed once in a 12-hour period.   
     
     
         16 . The drug product according to  claim 15 , wherein from about 54% to about 62% of the total amount of guaifenesin absorbed into the bloodstream is absorbed within 1.5 hours after administration under fasted conditions. 
     
     
         17 . The drug product according to  claim 15 , wherein about 48% of the total amount of guaifenesin absorbed into the bloodstream is absorbed within 1.5 hours after administration under fasted conditions. 
     
     
         18 . The drug product according to  claim 15 , wherein about 54% of the total amount of guaifenesin absorbed into the bloodstream is absorbed within 1.5 hours after administration under fasted conditions. 
     
     
         19 . The drug product according to  claim 15 , wherein about 62% of the total amount of guaifenesin absorbed into the bloodstream is absorbed within 1.5 hours after administration under fasted conditions. 
     
     
         20 . The drug product according to  claim 15 , wherein the first and second portions are discrete. 
     
     
         21 . The drug product according to  claim 20 , which is in a form of a bi-layer tablet. 
     
     
         22 . A drug product comprising 1200 mg of guaifenesin and having two portions,
 wherein a first portion comprises guaifenesin in an immediate release form, which releases guaifenesin in a human subject's stomach, and a second portion comprises guaifenesin in a sustained release form,   wherein from about 54% to about 66% of a total amount of guaifenesin absorbed into bloodstream is absorbed within 2 hours after administration under fasted conditions, and   wherein guaifenesin is absorbed into the bloodstream such that the drug product can be appropriately dosed once in a 12-hour period.   
     
     
         23 . The drug product according to  claim 22 , wherein from about 59% to about 66% of the total amount of guaifenesin absorbed into the bloodstream is absorbed within 2 hours after administration under fasted conditions. 
     
     
         24 . The drug product according to  claim 22 , wherein about 54% of the total amount of guaifenesin absorbed into the bloodstream is absorbed within 2 hours after administration under fasted conditions. 
     
     
         25 . The drug product according to  claim 22 , wherein about 59% of the total amount of guaifenesin absorbed into the bloodstream is absorbed within 2 hours after administration under fasted conditions. 
     
     
         26 . The drug product according to  claim 22 , wherein about 66% of the total amount of guaifenesin absorbed into the bloodstream is absorbed within 2 hours after administration under fasted conditions. 
     
     
         27 . The drug product according to  claim 22 , wherein the first and second portions are discrete. 
     
     
         28 . The drug product according to  claim 27 , which is in a form of a bi-layer tablet. 
     
     
         29 . A drug product comprising 1200 mg of guaifenesin and having two portions,
 wherein a first portion comprises guaifenesin in an immediate release form, which releases guaifenesin in a human subject's stomach, and a second portion comprises guaifenesin in a sustained release form,   wherein from about 63% to about 72% of a total amount of guaifenesin absorbed into bloodstream is absorbed within 3 hours after administration under fasted conditions, and   wherein guaifenesin is absorbed into the bloodstream such that the drug product can be appropriately dosed once in a 12-hour period.   
     
     
         30 . The drug product according to  claim 29 , wherein from about 67% to about 72% of the total amount of guaifenesin absorbed into the bloodstream is absorbed within 3 hours after administration under fasted conditions. 
     
     
         31 . The drug product according to  claim 29 , wherein about 63% of the total amount of guaifenesin absorbed into the bloodstream is absorbed within 3 hours after administration under fasted conditions. 
     
     
         32 . The drug product according to  claim 29 , wherein about 67% of the total amount of guaifenesin absorbed into the bloodstream is absorbed within 3 hours after administration under fasted conditions. 
     
     
         33 . The drug product according to  claim 29 , wherein about 72% of the total amount of guaifenesin absorbed into the bloodstream is absorbed within 3 hours after administration under fasted conditions. 
     
     
         34 . The drug product according to  claim 29 , wherein the first and second portions are discrete. 
     
     
         35 . The drug product according to  claim 34 , which is in a form of a bi-layer tablet. 
     
     
         36 . The drug product according to  claim 1 , wherein from about 39% to about 55% of a total amount of guaifenesin absorbed into the bloodstream is absorbed within 1 hour after administration under fasted conditions,
 wherein from about 48% to about 62% of a total amount of guaifenesin absorbed into the bloodstream is absorbed within 1.5 hours after administration under fasted conditions,   wherein from about 54% to about 66% of a total amount of guaifenesin absorbed into the bloodstream is absorbed within 2 hours after administration under fasted conditions, and   wherein from about 63% to about 72% of a total amount of guaifenesin absorbed into the bloodstream is absorbed within 3 hours after administration under fasted conditions.