Hydromorphone therapy
AssigneeAlza Corporation
InventorsSonya Merrill, Atul D. Ayer, Navjot Chadha, Anthony L. Kuczynski
Life of this patent
Estimating the term…
Abstract
A hydromorphone composition, a hydromorphone dosage form and a method for administering hydromorphone are disclosed, indicated for the management of pain.
Claims46
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.
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.
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.
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.
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.
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.
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 hydroxypropylalkylcellulose, 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 1 wt % poly(ethylene glycol);
- and, an exit in the semipermeable wall for delivering the hydromorphone to the patient to provide relief from pain.
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.
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.
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 layer comprising 63.672% poly(ethylene oxide) possessing a 2,000,000 molecular weight, 30.00% sodium chloride, 5% hydroxypropylmethylcellulose, 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.
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% hydroxypropylmethyl-cellulose, 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.
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.
A method for producing hydromorphone therapy in a patient, wherein the method comprises administering orally to the patient an extended-release pharmaceutical formulation comprising 1 mg to 500 mg of a member selected from the group consisting of hydromorphone and a 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 that produces a first plasma hydromorphone concentration, a second elevated plasma hydromorphone concentration, and a third continuous plasma hydromorphone concentration for producing hydromorphone therapy up to 24 hrs in the patient.
A method for providing a plasma concentration of hydromorphone in a patient, wherein the method comprises administering orally into gastrointestinal tract of the patient an extended-release pharmaceutical formulation comprising 1 mg to 500 mg of a member selected from the group consisting of hydromorphone and hydromorphone pharmaceutically acceptable salt in a pharmaceutically acceptable carrier that is delivered in 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 to produce from greater than zero ng/ml to twenty-five ng/ml plasma concentration of hydromorphone for up to 24 hrs of hydromorphone therapy.
Dependencies are inferred from the claim text.