Hydromorphone therapy

Abstract

A hydromorphone composition, a hydromorphone dosage form and a method for administering hydromorphone are disclosed, indicated for the management of pain.

1 . A dosage form comprising a drug layer comprising 8 mg of hydromorphone, 67.8 mg of poly(ethylene oxide) of 200,000 molecular weight, 4 mg of poly(vinyl pyrrolidone), and 0.2 mg of a lubricant; a delivery layer comprising 37.8 mg of poly(ethylene oxide) possessing a 2,000,000 molecular weight, 18 mg of sodium chloride, 3 mg of hydroxypropylmethyl-cellulose of 9,200 molecular weight, 0.6 mg of a colorant, and 0.15 mg of a lubricant; a semipermeable wall comprising 27.2 mg of cellulose acetate of 39.8% acetyl content, and 0.275 mg of polyethylene glycol of 3,350 molecular weight; a passageway in the wall; and a controlled rate of release of 0.427 mg/hr for 17.3 hours.  
     
     
         2 . A dosage form comprising 32 mg of hydromorphone, 119.6 mg of poly(ethylene oxide) possessing a 200,000 molecular weight, 8 mg of poly(vinyl pyrrolidone) of 42,000 molecular weight, and 0.4 mg of magnesium stearate; a delivery layer comprising 76.49 mg of poly(ethylene oxide) of 2,000,000 molecular weight, 36 mg of sodium chloride, 6 mg of hydroxypropylmethylcellulose of 9,200 molecular weight, 0.3 mg of magnesium stearate, 1.2 mg of a colorant, and 0.012 mg of an antioxidant; a semipermeable wall comprising 29.6 mg of cellulose acetate comprising an acetyl content of 39.8%, and 0.29 mg of polyethylene glycol possessing a 3,350 molecular weight, which wall surrounds the layers; a passageway in the dosage form; and a controlled rate of release of 1.811 mg/hr for 16.1 hours.  
     
     
         3 . A dosage form comprising 64 mg of hydromorphone, 138.6 mg of poly(ethylene oxide) possessing a 200,000 molecular weight, 10.7 mg of poly(vinyl pyrrolidone) of 42,000 molecular weight, and 0.53 mg of a lubricant; a delivery layer comprising 104.53 mg of poly(ethylene oxide) of 2,000,000 molecular weight, 49.2 mg of an osmagent, 8.2 mg of hydroxypropylmethylcellulose of 9,200 molecular weight, 1.64 mg of a colorant, 0.41 mg of a lubricant, and 0.123 mg of an antioxidant; a semipermeable wall comprising 38.61 mg of cellulose acetate comprising a 39.8% acetyl content, and 0.39 mg of polyethylene glycol of 3,350 molecular weight, which wall surrounds the layers; a passageway in the wall; and a controlled rate of release of 3.77 mg/hr of hydromorphone over 15.3 hours.  
     
     
         4 . A dosage form comprising 16 mg of hydromorphone, 135.6 mg of poly(ethylene oxide) of 200,000 molecular weight, 8 mg of poly(vinyl pyrrolidone) of 42,000 molecular weight, and 0.4 mg of a lubricant; a delivery layer comprising 76.49 mg of poly(ethylene oxide) of 2,000,000 molecular weight, 36 mg of an osmagent, 6 mg of hydroxypropylmethylcellulose of 9,200 molecular weight, 1.2 mg of a colorant, 0.3 mg of a lubricant, and 0.12 mg of an antioxidant; a semipermeable wall that surrounds the layers comprising 27.52 mg of cellulose acetate of 39.8% acetyl content, and 0.27 mg of polyethylene glycol of 3,350 molecular weight; a passageway in the dosage form; and a controlled rate of release of 0.957 mg/hr for 15.0 hours.  
     
     
         5 . A dosage form comprising: a drug layer comprising 8 mg of a member selected from the group consisting of hydromorphone and hydromorphone pharmaceutically acceptable salt, 84.70 wt % poly(ethylene oxide), 5 wt % poly (vinylpyrrolidone), 0.05 wt % butylated hydroxytoluene and 0.25 wt % magnesium stearate; an expandable layer comprising 63.675 wt % poly(ethylene oxide), 30 wt % of sodium chloride, 5 wt % of hydroxypropylmethylcellulose, 0.075 wt % of butylated hydroxytoluene, 1 wt % of a colorant, and 0.25 wt % of magnesium stearate; a semipermeable wall comprising 99 wt % cellulose acetate and 1 wt % polyethylene glycol that surrounds the drug and expansion layers; and, an exit in the wall for delivering hydromorphone from the dosage form.  
     
     
         6 . The dosage form according to  claim 5 , wherein the drug layer comprises 16 mg of a member selected from the group consisting of hydromorphone and a pharmaceutically acceptable salt.  
     
     
         7 . The dosage form according to  claim 5 , wherein the drug layer weighs 80 mgs.  
     
     
         8 . The dosage form according to  claim 6 , wherein the drug layer weighs 160 mg.  
     
     
         9 . The dosage form according to  claim 5 , wherein the expandable layer weighs 60 mg.  
     
     
         10 . The dosage form according to  claim 6 , wherein the expandable layer weighs 120 mg.  
     
     
         11 . The dosage form according to  claim 5 , wherein the dose of hydromorphone comprises 10 wt % of the drug layer.  
     
     
         12 . The dosage form according to  claim 6 , wherein the dose of hydromorphone comprises 10 wt % of the drug layer.  
     
     
         13 . The dosage form according to  claim 5 , wherein the expandable layer weighs 60 mg.  
     
     
         14 . The dosage form according to  claim 5 , wherein the expandable layer weighs 120 mg.  
     
     
         15 . A dosage form comprising: a drug layer comprising 32 mg of a member selected from the group consisting of hydromorphone and hydromorphone pharmaceutically acceptable salt, 74.75 wt % poly(ethylene oxide), 5 wt % poly(vinylpyrrolidone) and 0.25 wt % magnesium stearate, an expandable layer comprising 63.675 wt % poly(ethylene oxide), 30 wt % sodium chloride, 5 wt % hydroxypropylmethylcellulose, 0.075 butylated hydroxytoluene, 1 wt % colorant, and 0.25 wt % magnesium stearate; a semipermeable wall comprising 99 wt % cellulose acetate and 1 wt % poly(ethylene glycol), which wall surrounds the drug and expandable layers; and, an exit in the wall for delivering hydromorphone from the dosage form.  
     
     
         16 . The dosage form according to  claim 14 , wherein the drug layers weighs 160 mg.  
     
     
         17 . The dosage form according to  claim 14 , wherein the expandable layer weighs 120 mg.  
     
     
         18 . The dosage form according to  claim 14 , wherein the dose of hydromorphone is 20 wt % of the drug layer.  
     
     
         19 . A dosage form for delivering orally hydromorphone to a patient in need of relief from pain, wherein the dosage form comprises: a drug layer comprising 64 mg of a member selected from the group consisting of hydromorphone and its pharmaceutically acceptable salt, 64.75 mg of a poly(alkylene oxide), 5 wt % of a poly(vinylpyrrolidone) and 0.25 wt % of a lubricant; an expandable layer comprising 63.675 wt % of a poly(alkylene oxide), 30 wt % of an osmotically effective solute, 5 wt % of a hydroxypropyl-alkylcellulose, 0.075 wt % of an antioxidant, 1 wt % of a colorant, and 0.25 wt % of a lubricant; a semipermeable wall that surrounds the layers comprising 99 wt % cellulose acetate, and 0.1 wt % poly(ethylene glycol); and, an exit in the semipermeable wall for delivering the hydromorphone to the patient to provide relief from pain.  
     
     
         20 . The dosage form according to  claim 15 , wherein the drug layer weighs 214 mg.  
     
     
         21 . The dosage form according to  claim 15 , wherein the expandable layer weighs 164 mg.  
     
     
         22 . The dosage form according to  claim 15 , wherein the dose of hydromorphone is 30 wt % of the drug layer.  
     
     
         23 . A dosage form comprising a drug layer that weighs 80 mg and comprises 10.5% hydromorphone hydrochloride, 84.23% poly(ethylene oxide) having a 200,000 molecular weight, 5% poly(vinylpyrrolidone), 0.02% butylated hydroxytoluene, and 0.25% magnesium stearate; an expandable layer that weighs 60 mg and comprises 64.3% poly(ethylene oxide) possessing a 2,000,000 molecular weight, 30.00% sodium chloride, 5% hydroxypropylmethylcellulose, black iron oxide and lactose, 0.25% magnesium stearate, and 0.05 butylated hydroxytoluene; a membrane that surrounds the drug and expandable layers comprising 99% cellulose acetate and 1% polyethylene glycol; and an exit in the membrane for delivering the hydromorphone from the dosage form.  
     
     
         24 . The dosage form according to  claim 23 , wherein the dosage form comprises 0.4% or 1% of black iron oxide and lactose.  
     
     
         25 . The dosage form according to  claim 23  on, wherein the poly(vinylpyrrolidone) comprises a molecular weight of 38,000 to 42,000, the hydroxypropylmethylcellulose comprises a molecular weight of 9,200 to 11,300, and the expandable layer weighs 54 to 66 mg.  
     
     
         26 . The dosage form according to  claim 23  wherein the cellulose acetate comprises a 39.8% acetyl content and the polyethylene glycol comprises a 3,350 to 4,000 molecular weight.  
     
     
         27 . The dosage form according to  claim 23 , wherein the membrane is a wall and weighs 25 mg.  
     
     
         28 . A dosage form comprising a drug layer that weighs 152.4 mg and comprises 10.5% hydromorphone hydrochloride, 84.23% poly(ethylene oxide) of 200,000 molecular weight, 5% poly(vinylpyrrolidone), 0.02% butylated hydroxytoluene, and 0.25% magnesium stearate; an expandable layer comprising 64.3% poly (ethylene oxide) possessing a 2,000,000 molecular weight, 30.00% sodium chloride, 5% hydroxypropylmethylcellulose, black iron oxide and lactose, 0.25% magnesium stearate, and 0.05% butylated hydroxytoluene; a membrane that surrounds the layer and comprises 99% cellulose acetate and 1% polyethylene glycol; and an exit in the membrane for delivering the drug from the dosage form.  
     
     
         29 . The dosage form according to  claim 28 , wherein the dosage form comprises 0.4% or 1% of black iron oxide and lactose.  
     
     
         30 . The dosage form according to  claim 28 , wherein the poly(vinylpyrrolidone) comprises a 38,000 to 42,000 molecular weight, the hydroxypropylmethylcellulose comprises a 9,200 to 11,300 molecular weight, and the expandable layer weighs 122 to 134 mg.  
     
     
         31 . The dosage form according to  claim 28  wherein, the cellulose acetate comprises a 39.8% acetyl content, and the polyethylene glycol comprises a 3,350 to 4,000 molecular weight.  
     
     
         32 . The dosage form according to  claim 28 , wherein the membrane is a semipermeable wall and weighs 27 mg.  
     
     
         33 . The dosage form according to  claim 28 , wherein the black iron oxide and the lactose are present as a 95:5 mix.  
     
     
         34 . A dosage form comprising a drug layer that weighs 160 mg and comprises 20% hydromorphone hydrochloride, 74.68% poly(ethylene oxide) possessing a 200,000 molecular weight, 5% poly(vinylpyrrolidone), 0.02% butylated hydroxytoluene, and 0.25% magnesium stearate; an expandable  11  layer comprising 63.672% poly(ethylene oxide) possessing a 2,000,000 molecular weight, 30.00% sodium chloride, 5% hydroxypropylmethyl-cellulose, 1% black iron oxide and lactose, 0.25% magnesium stearate, and 0.05% butylated hydroxytoluene; a rate controlling membrane that surrounds both layers and comprises 99% cellulose acetate and 1% polyethylene glycol; and an exit in the membrane for delivering the drug from the dosage form.  
     
     
         35 . The dosage form according to  claim 34  wherein, the drug layer comprises 0.05% ferric oxide yellow.  
     
     
         36 . The dosage form according to  claim 34  wherein, the poly(vinylpyrrolidone) possesses a 38,000 to 42,000 molecular weight, the hydroxypropylmethylcellulose, and the expandable layer weighs 114 to 126 mg.  
     
     
         37 . The dosage form according to  claim 34  wherein, the cellulose acetate comprises an acetyl content of 39.8% and the polyethylene glycol comprises a 3,350 to 4,000 molecular weight.  
     
     
         38 . The dosage form according to  claim 34  wherein, the membrane is a semipermeable wall and weighs 29 mg.  
     
     
         39 . The dosage form according to  claim 34  wherein, the black iron oxide and lactose comprise a 95:5 mix and is a colorant.  
     
     
         40 . A dosage form comprising a drug layer that weighs 213.3 mg and comprises 30% hydromorphone hydrochloride, 64.73% poly(ethylene oxide) possessing a 200,000 molecular weight, 5% poly(vinylpyrrolidone), 0.02% butylated hydroxytoluene and 0.25% magnesium stearate; an expandable layer comprising 64.3% poly(ethylene oxide) possessing a 2,000,000 molecular weight, 30.003% sodium chloride, 5% hydroxypropylmethylcellulose, black iron oxide and lactose, 0.25% magnesium stearate, and 0.05% butylated hydroxytoluene; a membrane that surrounds the layers and comprises 99% cellulose acetate and 1% polyethylene glycol; and an exit in the membrane for delivering the hydromorphone from the dosage form.  
     
     
         41 . The dosage form according to  claim 40 , wherein the dosage form comprises 0.4% or 1% black iron oxide and 0.05% butylated hydroxytoluene.  
     
     
         42 . The dosage form according to  claim 40  wherein, the poly(vinylpyrrolidone) comprises a 38,000 to 42,000 molecular weight, the hydroxypropylmethylcellulose comprises a 9,200 to 11,300 molecular weight, and the expandable layer weighs 156 to 172 mg.  
     
     
         43 . The dosage form according to  claim 40  wherein, the cellulose acetate comprises an acetyl content of 39.8% and the polyethylene glycol comprises a 3,350 to 4,000 molecular weight.  
     
     
         44 . The dosage form according to  claim 40  wherein, the membrane is a semipermeable wall and weighs 40 mg.  
     
     
         45 . The dosage form according to  claim 40  wherein the black iron oxide and the lactose comprise a 95:5 mix, and is a colorant.  
     
     
         46 . An extended-release dosage form comprising 1 mg to 500 mg of a member selected from the group consisting of hydromorphone and hydromorphone pharmaceutically acceptable salt that is administered orally to a patient in an extended-release time up to 24 hrs for the relief of pain.  
     
     
         47 . An extended-release dosage form comprising 1 mg to 500 mg of a member selected from the group consisting of hydromorphone and its pharmaceutically acceptable salt that is administered orally to a patient in a dose of 0.04 mg/hr to 20 mg/hr up to 24 hrs for the relief of pain associated with an infection, surgery, cancer, trauma, colic, disease, infarction, burns, cold, cough, ulcer, hepatic, and renal pain.  
     
     
         48 . An extended-release pharmaceutical formulation comprising 1 mg to 500 mg of a total dose of a member selected from the group consisting of hydromorphone and hydromorphone pharmaceutically acceptable salt in a pharmaceutically acceptable carrier in a delivery dose pattern of from 0 to 20% in 0 to 4 hrs, 20 to 50% in 0 to 8 hrs, 55 to 85% in 0 to 14 hrs, and 80 to 100% in 0 to 24 hrs for achieving a therapeutically effective blood level over the delivery pattern.  
     
     
         49 . An extended-release pharmaceutical formulation comprising 1 mg to 500 mg dose of a member selected from the group consisting of hydromorphone and hydromorphone pharmaceutically acceptable salt that is delivered in a therapeutic dose of from 0 to 20% in 0 to 4 hrs, 20 to 50% in 0 to 8 hrs, 55 to 85% in 0 to 14 hrs, and 75 to 100% in 0 to 24 hrs for the relief of pain associated with infection, surgery, cancer, trauma, colic, disease, infarction, burns, cold, cough, ulcer, hepatic, and renal pain.  
     
     
         50 . A method of producing a plasma concentration of hydromorphone in a patient in need of hydromorphone, wherein the method comprises orally admitting into the patient a dosage form comprising 1 mg to 500 mg of hydromorphone that is administered as a controlled rate over a continuous time up to 24 hours for hydromorphone to enter the plasma for producing the intended hydromorphone therapy.  
     
     
         51 . A method for producing hydromorphone therapy in a patient, wherein the method comprises administering orally to the patient a dose of hydromorphone that produces a first plasma hydromorphone concentration, a second elevated plasma hydromorphone concentration, and a third continuous plasma hydromorphone concentration for producing hydromorphone therapy in the patient.  
     
     
         52 . A method for providing hydromorphone pain relief to a patient, wherein the method comprises orally administering to the patient an effective dose of hydromorphone that produces a first plasma level in from 0 to 8 hours, a second higher plasma, hydromorphone level in 8 to 12 hours, and a third extended plasma hydromorphone level in up to 24 hours to provide hydromorphone pain relief.  
     
     
         53 . A method for providing hydromorphone to a patient, wherein the method comprises admitting orally into the patient a dosage form comprising 10 to 100 mg of hydromorphone that is administered at a rate of 0.4 to 3.7 mg/hr up to 24 hrs for providing hydromorphone to the patient.  
     
     
         54 . A method for providing a plasma concentration of hydromorphone to a patient, wherein the method comprises administering orally into the gastrointestinal tract of the patient 2 to 75 mg of hydromorphone to produce from greater than zero ng/ml to twenty-five ng/ml plasma concentration.