Once-weekly oral administration of aripiprazole

Abstract

An orally deliverable pharmaceutical composition provides controlled release of aripiprazole. The composition includes a therapeutically effective amount of aripiprazole and at least one pharmaceutically acceptable excipient. The compositions of the invention may exhibit one or more of the release profiles defined in the specification.

1 . A method of treating a patient with one or more of a neurological and a psychiatric condition selected from the group consisting of a depressive disorder, an affective disorder, an addiction, attention deficit hyperactivity disorder and combinations thereof, the method comprising orally administering to the patient once weekly a pharmaceutical composition for the controlled release of aripiprazole, the pharmaceutical composition comprising a therapeutically effective amount of aripiprazole and at least one release-retarding material that retards the release of the aripiprazole such that the aripiprazole released from the composition is effective in treating the neurological or psychiatric condition for a period of one week. 
     
     
         2 . The method of  claim 1 , wherein the composition is formulated as a diffusion-controlled formulation, a dissolution-controlled formulation, an erosion-controlled formulation, an osmotic pump technology formulation, a sprinkle dosage formulation, an enteric-coated formulation, an ion exchange resin, or a combination thereof. 
     
     
         3 . The method of  claim 1 , wherein the composition is in the form of a capsule, tablet, liquid, powder, granule, suspension, matrix, microsphere, seed, pellet, bead or a combination of any two or more thereof. 
     
     
         4 . The method of  claim 1 , wherein the release retarding material is selected from the group consisting of a water-soluble synthetic polymer, a cellulose-based polymer, a hydrocolloid, a fatty acid, an alcohol, a wax, a water-insoluble biodegradable polymer, a plastic, a rubber, an ion-exchange resin, or a combination of two or more thereof. 
     
     
         5 . The method of  claim 4 , wherein the water-soluble synthetic polymer is selected from the group consisting of poly (acrylic acid), poly (ethylene oxide), poly (ethylene glycol), poly (vinyl pyrrolidone), poly (vinyl pyrrolidone) copolymers, poly (vinyl alcohol), polyacrylamide, poly (isopropyl acrylamide), poly (cyclopropyl methacrylamide), thermogelling acrylamide derivatives, carbomers, Carbopol® polymers, polyacrylic acid cross-linked with divinyl glycol, or a combination of two or more thereof. 
     
     
         6 . The method of  claim 4 , wherein the cellulose-based polymer is selected from the group consisting ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl butylcellulose, cellulose acetate phthalate, sodium carboxymethylcellulose, cellulose acetate, cellulose acetate butyrate, hydroxypropyl methycellulose phthalate, hydroxypropyl methycellulose succinate, cellulose acetate methylcarbamate, cellulose acetate ethylcarbamate, cellulose dimethylaminoacetate, or a combination of two or more thereof. 
     
     
         7 . The method of  claim 4 , wherein the hydrocolloid is selected from the group consisting alginic acid, sodium alginate, xanthan gum, carrageenan gum, hyaluronic acid, pectin, pectinic acid, guar gum, xylan gum, chitosan, locust bean gum, gellan gum, welan gum, rhamsan gum, algin gum, guar, acacia, karaya, tragacanth, starch, or a combination of two or more thereof. 
     
     
         8 . The method of  claim 4 , wherein the fatty acid, alcohol or wax is selected from the group consisting hydrogenated castor oil, hydrogenated vegetable oil, glyceryl behenate, glyceryl monostearate, stearic acid, cetyl alcohol, cetostearyl alcohol, carnauba wax, beeswax, polyoxyglycerides, glycerol esters, oleyl glycerate, glyceryl monooleate, selachyl alcohol, cocoa butter, cocoa butter propylene glycol monostearate, cocoa butter propylene glycol distearate, hydrogenated fat, hardened oil or fat, stearyl alcohol, glycowax, castor wax, dextran, shellac, tribehenin, C 16-30  fatty acid triglycerides, or a combination of two or more thereof. 
     
     
         9 . The method of  claim 4 , wherein the water-insoluble biodegradable polymer is selected from the group consisting poly (lactide-co-glycolide), polylactic acid, polyglycolic acid, or a combination of two or more thereof. 
     
     
         10 . The method of  claim 4 , wherein the plastic or rubber is selected from the group consisting polyurethane, silicones, polycarbonate, polychloroprene, polyisobutylene, polycyanoacrylate, poly (vinyl acetate), poly (vinyl acetate) copolymers, poly (vinyl acetate) phthalate, poly (vinyl chloride), polyethylene, poly (methyl methacrylates), poly (methyl methacrylate) copolymers, ethoxyethyl methacrylate, cyanoethyl methacrylate, aminoalkyl methacrylate copolymer, poly(methacrylic acid), methacrylic acid alkylamide copolymer, poly(methacrylic acid anhydride), poly (hydroxyethyl methacrylate), polyacrylamide, acrylic acid and butyl acrylate copolymer, 2-ethylhexyl acrylate and butyl acrylate copolymer, vinyl acetate and methyl acrylate copolymer, polyurethane hydrogel, semipermeable polyamide, semipermeable polyurethane, semipermeable polysulfane, semipermeable sulfonated polystyrene, semipermeable silicon rubber, semipermeable poly (sodium styrenesulfonate), semipermeable poly(vinylbenzyltrimethyl) ammonium chloride, or a combination of two or more thereof. 
     
     
         11 . The method of  claim 4 , wherein the ion-exchange resin is selected from the group consisting styrene/divinylbenzene resin and methacrylic acid/divinylbenzene resin, or a combination of two or more thereof. 
     
     
         12 . The method of  claim 1 , wherein the composition comprises at least one pharmaceutically active agent in addition to aripiprazole. 
     
     
         13 . The method of  claim 12 , wherein the at least one additional pharmaceutically active agent is selected from the group consisting of one or more atypical antipsychotic agent, antiparkinsonian agent, sedative, anxiolytic, antidepressant, monoamine oxidase A or B inhibitor, tetracyclic antidepressant, serotonin re-uptake inhibitor, noradrenaline reuptake inhibitor, adrenaline reuptake inhibitor, and mood stabilizer, or a combination of two or more thereof. 
     
     
         14 . The method of  claim 1 , wherein the treatment is associated with the partial agonist properties of aripiprazole on neurotransmitter pathways in the brain. 
     
     
         15 . The method of  claim 1 , wherein one or more of the neurological and a psychiatric condition is associated with dopamine receptors. 
     
     
         16 . A method of treating a patient with one or more of a neurological and a psychiatric condition selected from the group consisting of a depressive disorder, an affective disorder, an addiction, attention deficit hyperactivity disorder and combinations thereof, the method comprising orally administering to the patient once weekly a pharmaceutical composition for the controlled release of aripiprazole, the pharmaceutical composition comprising a therapeutically effective amount of aripiprazole and at least one release-retarding material comprising a water-swellable polymer that forms a matrix that retards the release of the aripiprazole such that the aripiprazole released from the composition is effective in treating the neurological or psychiatric condition for a period of one week. 
     
     
         17 . A method of treating a patient with one or more of a neurological and a psychiatric condition selected from the group consisting of schizophrenia, bipolar disorder, schizoaffective disorders, and combinations thereof, the method comprising orally administering to the patient once weekly a pharmaceutical composition for the controlled release of aripiprazole, the pharmaceutical composition comprising a therapeutically effective amount of aripiprazole and at least one release-retarding material that retards the release of the aripiprazole such that the aripiprazole released from the composition is effective in treating the neurological or psychiatric condition for a period of one week, wherein the release retarding material is selected from the group consisting of a water-soluble synthetic polymer, a cellulose-based polymer, a hydrocolloid, a fatty acid, an alcohol, a wax, a water-insoluble biodegradable polymer, a plastic, a rubber, an ion-exchange resin, or a combination of two or more thereof.