Osmotic drug delivery system

Abstract

An oral osmotic pharmaceutical delivery system comprises a highly water-soluble drug exhibiting an erratic or an incomplete release profile when formulated in a elementary osmotic pump delivery system and at least one release enhancing agent.

1 - 49 . (canceled) 
     
     
         50 . An oral osmotic pharmaceutical delivery composition comprising a therapeutically effective amount of treprostinil or a pharmaceutically acceptable salt thereof and at least one release enhancing agent, which has a plasma concentration T max  (time to reach C max ) after administration of from 2 hours to 8 hours. 
     
     
         51 . An oral osmotic pharmaceutical delivery composition of  claim 50 , wherein the therapeutically effective plasma concentration of treprostinil or its salt after administration has a C min  of 0.1 ng/ml to 0.2 ng/ml. 
     
     
         52 . An oral osmotic pharmaceutical delivery composition of  claim 50 , wherein the therapeutically effective plasma concentration of treprostinil or its salt after administration has a C max  of 0.5 ng/ml to 2 ng/ml. 
     
     
         53 . An oral osmotic pharmaceutical delivery composition of  claim 50 , wherein the therapeutically effective plasma concentration of treprostinil or its salt after administration is maintained to allow for a twice-a-day to once-a-day administration. 
     
     
         54 . An oral osmotic pharmaceutical delivery composition of  claim 53 , wherein the therapeutically effective plasma concentration of treprostinil or its salt after administration is maintained to allow for a twice-a-day administration. 
     
     
         55 . An oral osmotic pharmaceutical delivery composition of  claim 50 , wherein the treprostinil or a pharmaceutically acceptable salt thereof has an aqueous solubility of at least 30 mg/ml. 
     
     
         56 . An oral osmotic pharmaceutical delivery composition of  claim 50 , wherein the treprostinil or a pharmaceutically acceptable salt thereof comprises treprostinil diethanolamine. 
     
     
         57 . An oral osmotic pharmaceutical delivery composition of  claim 50 , wherein the release enhancing agent is selected from a group consisting of wicking agents, complexing agents, and micelle-forming agents. 
     
     
         58 . An oral osmotic pharmaceutical delivery composition of  claim 50 , further comprising at least one osmotic agent. 
     
     
         59 . An oral osmotic pharmaceutical delivery composition of  claim 50 , wherein the release enhancing agent comprises at least one agent selected from a group consisting of polyethylene oxide-polypropylene oxide block copolymers, cellulose ethers, and polyethylene glycols. 
     
     
         60 . An oral osmotic pharmaceutical delivery composition of  claim 50 , wherein the release enhancing agent comprises at least one agent selected from a group consisting of high HLB surfactants, ionic surfactants, and non-swelling hydrophilic polymers 
     
     
         61 . An oral osmotic pharmaceutical delivery composition of  claim 50 , wherein the release enhancing agent comprises at least one agent selected from a group consisting of polyvinyl pyrrolidone, cyclodextrins, and non-ionic surface active agents 
     
     
         62 . An oral osmotic pharmaceutical delivery composition of  claim 50 , wherein the release enhancing agent comprises at least one agent selected from a group consisting of poly(ethylene oxide) modified sorbitan monoesters, fatty acid sorbitan esters, sodium lauryl sulfate, and sodium docusate. 
     
     
         63 . An oral osmotic pharmaceutical delivery composition of  claim 50 , wherein 
     
     
         64 . A method of treating pulmonary hypertension comprising administering to a human subject in need thereof a composition of  claim 50 . 
     
     
         65 . A method of reducing one or more side effects in a human subject comprising administering an effective amount of an oral osmotic pharmaceutical delivery composition comprising a therapeutically effective amount of treprostinil or a pharmaceutically acceptable salt thereof and at least one release enhancing agent. 
     
     
         66 . The method of  claim 65 , wherein the treprostinil or pharmaceutically acceptable salt thereof is treprostinil diethanolamine. 
     
     
         67 . An oral pharmaceutical composition for extended release of treprostinil or a pharmaceutically acceptable salt thereof, comprising a therapeutically effective amount of treprostinil or a pharmaceutically acceptable salt thereof and at least one release enhancing agent, so that when ingested orally, the composition induces statistically significantly lower mean fluctuation index in the plasma than an immediate release composition of the treprostinil or pharmaceutically acceptable salt thereof, while maintaining or improving bioavailability to that of the immediate release composition of treprostinil or pharmaceutically acceptable salt thereof. 
     
     
         68 . The composition of  claim 67 , wherein the treprostinil or pharmaceutically acceptable salt thereof is treprostinil diethanolamine. 
     
     
         69 . The composition of  claim 67 , wherein the oral pharmaceutical composition for extended release of treprostinil or a pharmaceutically acceptable salt thereof is an oral osmotic pharmaceutical delivery composition.