Formulations of viloxazine

Abstract

Modified release formulations of viloxazine and methods of administering the same are disclosed. High-drug load formulations of viloxazine are further disclosed.

1 . A modified release formulation of viloxazine in which viloxazine is a sole active pharmaceutical ingredient, wherein said formulation comprises at least one of an extended release component and a delayed release component,
 wherein said extended release component comprises a core comprising viloxazine, and a coating of a release rate controlling compound on top of the core(s), and at least one pharmaceutically acceptable excipient, wherein the delayed release component comprises a core comprising viloxazine and a coating of an enteric compound on top of the core(s),   and wherein the enteric compound has solubility that is pH-dependent and is selected from a group consisting of poly (methyl acrylate-co-methyl methacrylate-co-methacrylic acid), poly (methacrylic acid-co-methyl methacrylate), hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, shellac, and zein,   wherein the release rate controlling compound is a hydrophilic compound selected from the group consisting of hydroxypropyl cellulose; hydroxypropyl methyl cellulose; methyl cellulose; polyethylene oxide; acacia; acrylic acid derivatives; alginic acid and its salts; hydroxyethyl cellulose; povidone; carrageenan; carboxymethylcellulose; tragacanth; polyvinyl alcohol; xanthan gum, and combinations thereof,   or a hydrophobic compound selected from the group consisting of ethylcellulose; cellulose acetate; cellulose acetate butyrate; waxes; hydrogenated vegetable oils; glyceryl behenate; glyceryl palmitostearate; PEG glyceryl esters; poly(ethyl acrylate-co-methyl methacrylate) ethyl acrylate methyl methacrylate copolymer; poly (ethyl acrylate-co-methyl methacrylate-cotrimethylammonioethyl methacrylate chloride); polyvinyl acetate; cellulose acetate propionate, and combinations thereof;   wherein the formulation comprises from 5% (w/w) to 65% (w/w) of the release rate controlling compound, from 5% (w/w) to 50% (w/w) of the enteric compound, and 25% (w/w) to 75% (w/w) of viloxazine.   
     
     
         2 . A modified release formulation of viloxazine in which viloxazine is a sole active pharmaceutical ingredient, wherein said formulation comprises at least one of an extended release component and a delayed release component,
 wherein said extended release component comprises a matrix core, wherein the matrix core comprises an admixture of viloxazine and the release rate controlling compound, and at least one pharmaceutically acceptable excipient, wherein the delayed release component comprises a core comprising viloxazine and a coating of an enteric compound on top of the core(s), and wherein the enteric compound is a compound having solubility that is pH-dependent and is selected from a group consisting of poly (methyl acrylate-co-methyl methacrylate-co-methacrylic acid), poly (methacrylic acid-co-methyl methacrylate), hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, shellac, and zein,   wherein the release rate controlling compound is a hydrophilic compound selected from the group consisting of hydroxypropyl cellulose; hydroxypropyl methyl cellulose; methyl cellulose; polyethylene oxide; acacia; acrylic acid derivatives; alginic acid and its salts; hydroxyethyl cellulose; povidone; carrageenan; carboxymethylcellulose; tragacanth; polyvinyl alcohol; xanthan gum, and combinations thereof,   or a hydrophobic compound selected from the group consisting of ethylcellulose; cellulose acetate; cellulose acetate butyrate; waxes; hydrogenated vegetable oils; glyceryl behenate; glyceryl palmitostearate; PEG glyceryl esters; poly(ethyl acrylate-co-methyl methacrylate) ethyl acrylate methyl methacrylate copolymer; poly (ethyl acrylate-co-methyl methacrylate-cotrimethylammonioethyl methacrylate chloride); polyvinyl acetate; cellulose acetate propionate, and combinations thereof;   wherein the formulation comprises from 5% (w/w) to 50% (w/w) of the enteric compound, and 25% (w/w) to 75% (w/w) of viloxazine.   
     
     
         3 . The formulation of  claim 1 , comprising from 10 mg to 800 mg of viloxazine. 
     
     
         4 . The formulation of  claim 1  for once-a-day administration. 
     
     
         5 . The formulation of  claim 1  for twice-a-day administration. 
     
     
         6 . The formulation of  claim 4  having a reduced level of at least one undesirable side effect as compared to the same amount of viloxazine administered as an immediate release formulation BID or TID. 
     
     
         7 . The formulation of  claim 6  wherein the undesirable side effect is selected from gastrointestinal side effects and neurological side effects. 
     
     
         8 . The formulation of  claim 7  wherein the undesirable gastrointestinal side effects include dyspepsia, nausea and vomiting. 
     
     
         9 . The formulation of  claim 7  wherein the undesirable neurological side effects comprise sleep disturbances. 
     
     
         10 . The formulation of  claim 9 , wherein the sleep disturbances are selected from insomnia and/or abnormal dreams. 
     
     
         11 . The formulation of  claim 1  in a dosage form selected from tablets, capsules, beads, granules, powders, caplets, troches, sachets, cachets, pouches, gums, sprinkles and suspensions. 
     
     
         12 . The formulation of  claim 1  comprising at least two extended release cores, wherein each extended release core has its own rate of release. 
     
     
         13 . A method of treating a CNS disorder in a mammalian subject in need thereof, the method comprising administration to the subject an effective amount of a formulation of  claim 1 . 
     
     
         14 . The method of  claim 13 , wherein the CNS disorder is selected from ADHD, ADHD related disorders and major depressive disorder. 
     
     
         15 . The method of  claim 13 , wherein the formulation is administered once a day. 
     
     
         16 . The method of  claim 13 , wherein the formulation is administered twice a day. 
     
     
         17 . The method of  claim 13 , wherein the administration results in a reduced level of at least one undesirable side effect as compared to the same amount of viloxazine administered as an immediate release formulation BID or TID. 
     
     
         18 . The method of  claim 17 , wherein the undesirable side effect is selected from gastrointestinal side effects and neurological side effects. 
     
     
         19 . The method of  claim 18 , wherein the undesirable gastrointestinal side effects include dyspepsia, nausea and vomiting. 
     
     
         20 . The method of  claim 18 , wherein the undesirable neurological side effects include sleep disturbances. 
     
     
         21 . The method of  claim 20 , wherein the sleep disturbances are selected from insomnia and/or abnormal dreams. 
     
     
         22 . The method of  claim 13 , wherein the subject is a human child. 
     
     
         23 . The method of  claim 13 , wherein the subject is a human adult. 
     
     
         24 . The method of  claim 13 , wherein the formulation is administered in a daily dose of from 10 mg to 800 mg. 
     
     
         25 . The method of  claim 13 , wherein the amount of viloxazine in the formulation is from 25% (w/w) to 75% (w/w). 
     
     
         26 . The formulation of  claim 1 , wherein the formulation is a gastro-retentive formulation.