Patent ID: 8716337

Claim:
A method for forming an improved drug system with an optimized bioavailability comprising the steps of: forming a drug substance consisting essentially of A-B-C wherein A is an amine containing pharmaceutically active compound; C is a first dissolution modifying amine and B is a bidentate linking group used to covalently or ionically link A and C defined by the formula: wherein Y 1 and Y 2 are independently selected from nitrogen oxygen and sulfur; R 10 and R 11 are present when necessary to satisfy the valence of Y 1 and Y 2 , respectively, and are independently selected from hydrogen and an alkyl of 1-6 carbons; aryl of 6-12 carbons, alkylacyl of 1-8 carbons or arylacyl 7-15 carbons; G 1 and G 2 independently represent ionically or covalently bound groups; R 12 and R 13 are independently selected from hydrogen, alkyl or 1-6 carbons, alkylacyl of 1-8 carbons or arylacyl of 7-15 carbons; R 14 will replace one of R 15 , R 16 , R 17 or R 18 and one of R 19 , R 20 , R 21 or R 22 and is an alkyl or branched alkyl of 1-10 carbons, aryl, arylalkyl of 7-15 carbons and wherein R 14 may include at least one optically active carbon; and R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 and R 22 , are independently selected from hydrogen, alkyl of 1-6 carbons, and wherein adjacent groups may be taken together to form a cyclic alkyl or cyclic aryl moiety; measuring a dissolution profile at pH intervals representing gastric, intestinal and aqueous conditions; comparing said dissolution profiles against a predetermined standard; forming a second drug substance consisting essentially of A-B-C′ wherein A is said amine containing pharmaceutically active compound; C′ is a second dissolution modifying amine and B is said bidentate linking group used to covalently or ionically link A and C wherein said second dissolution modifying amine has a different hydrophilicity than said first dissolution modifying amine; and measuring a second dissolution profile of said second drug substance at pH intervals representing gastric, intestinal and aqueous conditions wherein at least one of said first dissolution modifying amine or said second dissolution modifying amine is defined by the formula: NR 23 R 24 R 25 wherein at least one of R 23 , R 24 or R 25 is not hydrogen and R 23 , R 24 and R 25 are independently selected hydrogen, alkyl of 1-60 carbons; cyclic alkyl of 3-22 carbons; polyoxyalkylene with 1-5 carbons per oxyalkylene monomeric unit or polyoxyarylene with 8-12 carbons per oxyarylene monomeric unit wherein at least one of said R 23 , R 24 or R 25 comprises a polymerized monomeric units selected from the group consisting of ethylene oxide, propylene oxide, butylene oxide and styrene oxide.