Connect public, paid and private patent data with Google Patents Public Datasets

Hydrocodone therapy

Download PDF

Info

Publication number
US20030077320A1
US20030077320A1 US10267500 US26750002A US2003077320A1 US 20030077320 A1 US20030077320 A1 US 20030077320A1 US 10267500 US10267500 US 10267500 US 26750002 A US26750002 A US 26750002A US 2003077320 A1 US2003077320 A1 US 2003077320A1
Authority
US
Grant status
Application
Patent type
Prior art keywords
hydrocodone
mg
composition
weight
molecular
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US10267500
Inventor
Jerry Childers
George Guittard
Glen Barclay
Anthony Kuczynski
Patrick Wong
Original Assignee
Childers Jerry D.
Guittard George V.
Barclay Glen E.
Kuczynski Anthony L.
Wong Patrick S.-L.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/2031Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47Quinolines; Isoquinolines
    • A61K31/485Morphinan derivatives, e.g. morphine, codeine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0002Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0004Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/205Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Abstract

A hydrocodone composition, a hydrocodone dosage form, and a method of administering hydrocodone are disclosed and indicated for hydrocodone therapy.

Description

    FIELD OF THE INVENTION
  • [0001]
    This invention pertains to a novel therapeutic composition comprising hydrocodone. The invention concerns also a novel dosage form comprising hydrocodone. Additionally, the invention relates to a novel method of administering a dose of hydrocodone from a therapeutic composition, and to a novel method of administering a dose of hydrocodone from a dosage form that in both administrations are for producing antitussive and analgesic therapy.
  • BACKGROUND OF THE INVENTION
  • [0002]
    Hydrocodone is chemically 4,5-epoxy-3-methoxy-17-methyl-morphinan-6-one. The synthesis of hydrocodone and its pharmaceutically acceptable acid addition salts are described in U.S. Pat. No. 2,71 5,629 issued to Pfister et al, and in the Merck Index, 11th Edition, page 757, entry 4708 (1989). Hydrocodone is a narcotic antitussive and analgesic. The mechanism of physiological and pharmacological actions of hydrocodone is believed that it acts directly by depressing the cough centers for its antitussive therapy. At antitussive doses, hydrocodone exerts also analgesic effects. Hydrocodone exhibits a complex pattern of metabolism including O-demethylation, N-dimethylation and 6-keto reduction to the corresponding 6-β-hydroxy metabolites.
  • [0003]
    The prior art administers hydrocodone in conventional tablet and syrup forms, which forms dose-dump hydrocodone thereby providing a concentration of hydrocodone followed by an absence of hydrocodone. This pharmaceodynamic variability with its fluctuation in hydrocodone availability to hydrocodone receptor sites produces uncertainty as it is unknown if a dose of hydrocodone is present for needed therapy. The prior art is deficient in providing controlled hydrocodone therapy to a patient seeking such therapy. The pharmacological properties of hydrocodone are known in The Pharmacological Basis of Therapy, by Gilman and Rall, 8th Edition, pg. 497, (1990); and in Pharmaceutical Sciences, Remington, 17th Ed., pg. 1104, (1985).
  • SUMMARY OF THE INVENTION
  • [0004]
    In view of the foregoing presentation, it is immediately apparent that a present and critical need exists for an improvement in the delivery of hydrocodone for its therapeutic antitussive and analgesic effects. The need exists for providing a novel therapeutic composition comprising hydrocodone, the need exists for providing a novel dosage form comprising hydrocodone, and the need exists for providing a novel method for administering hydrocodone to a patient in need of hydrocodone therapy. It is, therefore, an object of this invention to provide a therapeutic composition comprising hydrocodone with means for enhancing the administration of hydrocodone over time. It is also an object of the invention to provide a dosage form with means for controlling the delivery of hydrocodone that overcomes fluctuation in hydrocodone therapy. It is an additional object of the invention to provide a method for administering hydrocodone for better hydrocodone therapy.
  • DESCRIPTION OF THE INVENTION
  • [0005]
    The drug hydrocodone, as embraced by this invention, comprises a member selected from the group consisting of hydrocodone and its pharmaceutically acceptable salts. Representative of hydrocodone pharmaceutically acceptable salts comprises a member selected from the group consisting of hydrocodone bitartrate, hydrocodone bitartrate hydrate, hydrocodone hydrochloride, hydrocodone p-toluenesulfonate, hydrocodone phosphate, hydrocodone thiosemicarbazone, hydrocodone sulfate, hydrocodone trifluoroacetate, hydrocodone, hydrocodone bitartrate, dihydrocodeinone bitartrate, hydrocodone bitartrate hemipentahydrate, pentafluoropropionate, hydrocodone p-nitrophenylhydrazone, hydrocodone o-methyloxime, hydrocodone semicarbazone, hydrocodone hydrobromide, hydrocodone mucate, hydrocodone oleate, hydrocodone phosphate dibasic, hydrocodone phosphate monobasic, hydrocodone inorganic salt, hydrocodone organic salt, hydrocodone acetate trihydrate, hydrocodone bis(heptafuorobutyrate), hydrocodone bis(methylcarbamate), hydrocodone bis(pentafluoropropionate), hydrocodone bis(pyridine carboxylate), hydrocodone bis(trifluoroacetate), hydrocodone chlorhydrate, and hydrocodone sulfate pentahydrate.
  • [0006]
    The following examples are merely illustrative of the invention, and they should not be considered as limiting the scope of the invention in any way as these examples and other equivalents thereof will become more apparent to those versed in the art.
  • EXAMPLE 1
  • [0007]
    A novel, therapeutic composition comprising hydrocodone, wherein the hydrocodone is a member selected from the group consisting of hydrocodone pharmaceutically acceptable base and hydrocodone pharmaceutically acceptable salt is prepared as follows: first, 3.00 g of hydrocodone bitartrate hemipentahydrate, 6.45 g of poly(ethylene oxide) possessing a 200,000 molecular weight and 0.50 g of hydroxypropylmethylcellulose possessing a 11,200 molecular weight are dry blended on a roll mill at 50% of the maximum speed for 5 minutes. Then, 7 ml of denatured ethyl alchohol and the dry blend are slowly mixed together with a spatula for 5 minutes. After drying, the wetted mass is passed through a 0.03331 inch (0.85 mm) screen, and it is dried overnight at room temperature. Next, 0.049 g of magnesium stearate is blended with the granulation for 2 minutes on a roll mill at 50% of maximum speed. Then, a series of extended delivery {fraction (11/32)} inch (8.73 mm) round tablets are prepared by compressing the composition with a 1⅛-ton compression force. The high compression force imparts an increase in density and hardness and a decrease in fluid penetrability of the tablet thereby imparting extended delivery to the hydrocodone tablet. This hydrocodone tablet comprises 60 mg of hydrocodone bitartrate hemipentahydrate, 81.75 mg of poly(ethylene oxide), 7.5 mg of hydroxypropylmethylcellulose, and 0.75 mg of magnesium stearate.
  • EXAMPLE 2
  • [0008]
    The therapeutic composition manufactured by following the above example provides compositions comprising 0.5 mg to 1250 mg of a member selected from the group consisting of hydrocodone and hydrocodone pharmaceutically acceptable salt; 10 to 350 mg of a polymeric carrier for the hydrocodone selected from a poly(alkylene oxide) comprising a 75,000 to 400,000 molecular weight selected from poly(methylene oxide), poly(ethylene oxide), poly(propylene oxide), poly(isopropylene oxide) and poly(butylene oxide), and 5 to 50 mg of a hydroxyalkylcellulose or a hydroxypropylalkylcellulose possessing a 9,000 to 150,000 molecular weight as represented by a member selected from the group consisting of hydroxyethylcellulose, hydroxypropylmethylcellulose, hydroxypropylethylcellulose, hydroxypropylisopropylcellulose, hydroxypropylbutylcellulose, and hydroxypropylpentylcellulose; and 0.01 to 5 mg of a lubricant selected from the group consisting of magnesium stearate, calcium stearate, potassium oleate, sodium stearate, stearic acid, sodium palmitate, corn starch, potato starch, bentonite, citrus pulp, and stearic acid.
  • EXAMPLE 3
  • [0009]
    Following the procedures of Examples 1 and 2, the hydrocodone composition is encapsulated with a semipermeable polymeric composition provided with a hydrocodone-releasing orifice to provided an extended delivery dosage form.
  • EXAMPLE 4
  • [0010]
    A novel dosage form for delivering hydrocodone substantially free of delivery fluctuation is prepared as follows: first, 3.00 g of hydrocodone bitratrate hemipentahydrate, 6.45 g of poly(ethylene oxide) possessing a 200,000 molecular weight, and 0.50 g of hydroxypropylmethylcellulose possessing a 11,200 molecular weight are dry blended on a roll mill at 50% of the maximum speed for 5 minutes. Then, 7 ml of denatured ethyl alcohol and the dry blend are slowly mixed together for 5 minutes. After drying, this wetted mass is passed through a 0.03331 inch (0.85 mm) screen, and then dried overnight at room temperature. Next, 0.049 g of magnesium stearate is blended with the granulation for 2 minutes on a roll mill at 50% of maximum speed. Then, a number of {fraction (11/32)} inch (8.73 mm) tablets are compressed with 1-ton compression force. Each tablet contains 194 mg of hydrocodone drug granulation.
  • [0011]
    Next, a displacement or push composition comprising 25 to 300 mg of poly(ethylene oxide) of 3,500,000 to 7,500,000 molecular weight, 5 to 150 mg of an osmagent, 0 to 30 mg of a hydroxypropylcellulose of 9,200 to 175,000 molecular weight, 0 to 10 mg of ferric oxide, 0 to 10 mg of lubricant, and 0 to 3.5 mg of antioxidant is prepared according to the examples. An embodiment of the displacement or push composition comprises 47.76 mg of poly(ethylene oxide) of 7,000,000 molecular weight, 22.5 mg of osmagent sodium chloride, 3.75 mg of hydroxypropylmethylcellulose of 11,200 molecular weight, 0.18 mg of ferric oxide, 0.75 mg of magnesium stearate, and 0.06 mg of butytlated hydroxytolune is prepared by the accompanying procedure.
  • [0012]
    The push granulation is fluid bed granulated at 120 kg scale on a fluid bed granulator. A binder solution is made by dissolving hydroxypropylmethylcellulose, butylated hydroxytoluene in water and ethanol. This binder solution is sprayed onto the poly(ethylene oxide), sodium chloride, hydroxypropylmethylcellulose and ferric oxide blend, while the blend is fluidized and is forming granules. After the granulation is dried, the granulation is milled in a fluid air mill. Next, a lubricant magnesium stearate is added to the dry granulation.
  • [0013]
    A semipermeable composition comprising 80:19:1, wt:wt:wt, mixture of cellulose acetate comprising an acetyl content of 39.8%, poly(vinylpyrrolidone) and triethylcitrate dissolved in an 80:20, v:v, mixture of acetone and methanol at 4% solids is sprayed around the bilayer core comprising a compressed layer of hydrocodone composition and a compressed layer of push composition to provide a compressed bilayer, to apply the semipermeable wall. Next, a 25 mil (0.64 mm) orifice is drilled into each dosage form and the dosage form dried overnight at 40° celsius. The semipermeable wall weighed 35 mg. The dosage form has a mean release rate of 6.44 mg/hr over 15 hours.
  • EXAMPLE 5
  • [0014]
    Following the above procedure, dosage forms are provided possessing a hydrocodone rate of release of 0.5 mg to 10 mg per hour over 20 hours.
  • EXAMPLE 6
  • [0015]
    The osmagent for the purpose of this invention in the hydrocodone and push compositions comprises a member selected from the osmotic solutes consisting of magnesium sulfate, sodium chloride, lithium chloride, potassium sulfate, sodium sulfate, lithium sulfate, potassium acid phosphate, mannitol, urea, inositol, magnesium succinate, tartaric acid, carbohydrates like raffinose, sucrose, glucose, lactose, fructose, sodium chloride, and fructose, and potassium chloride and dextrose.
  • EXAMPLE 7
  • [0016]
    The procedures above described are followed for the controlled delivery of hydrocodone at a metered rate is prepared wherein the dosage form comprises a hydrocodone layer comprising 58.08 mg of hydrocodone bitartrate hemipentahydrate, 125.06 mg of poly(ethylene oxide) possessing a 200,000 molecular weight, 9.8 mg of hydroxypropylmethylcellulose of 9,400 molecular weight, and 0.97 mg of magnesium stearate. A push layer comprising 47.76 mg of poly(ethylene oxide) possessing a 7,000,000 molecular weight, 22.5 mg of osmotic solute sodium chloride, 3.75 mg of hydroxypropylmethylcellulose of 11,200 molecular weight, 0.75 mg of magnesium stearate, 0.18 mg of ferric oxide and 0.06 mg of butylated hydroxytoluene. The bilayer compositions are surrounded by a semipermeable wall comprising 25.92 mg of cellulose acetate comprising 39.8% acetyl content, 6.15 mg of poly(vinylpyrrolidone) of 40,000 molecular weight and 0.324 mg of plasticizer triethyl citrate. The dosage forms comprise a 25 mil (0.64 mm) orifice and exhibits a mean release rate of 5.105 mg/hr of hydrocodone over a sustained period of therapy over 16 hours.
  • EXAMPLE 8
  • [0017]
    The procedures of the above examples are followed to produce a hydrocodone composition comprising 60.00 mg of hydrocodone bitartrate hemipentahydrate, 81.75 mg of poly(ethylene oxide) of 200,000 molecular weight, 7.50 mg of hydroxypropylmethylcellulose of 9,200 molecular weight, and 0.75 mg of magnesium stearate. The semipermeable wall that surrounded the hydrocodone comprises 75:24:1, wt:wt:wt, mixture of cellulose acetate with an acetyl content of 39.8%, poly(vinylpyrrolidone) of 40,000 molecular weight and triethyl citrate. The semipermeable composition is dissolved in a 80:20, v:v, mixture of acetone and methanol at 4% solids. The semipermeable wall weighed 43.4 mg.
  • EXAMPLE 9
  • [0018]
    Representative of antioxidants for providing the dosage forms of this invention comprise a member selected from the group consisting of d-alpha tocopherol, dl-alpha tocopherol, d-alpha-tocopherol acetate, dl-alpha-tocopherol, ascorbyl palmitate, ascorbic acid, butylated hydroxyanisole, butylated hydroxytoluene, and propyl gallate.
  • EXAMPLES 10-11
  • [0019]
    The procedure of the above examples is followed except in these examples there is provided in one manufacture a hydrocodone composition comprising a poly(ethylene oxide) consisting of a 100,000 molecular weight, and in another manufacture the hydrocodone composition comprises the hydrocodone composition comprising a poly(ethylene oxide) of 300,000 molecular weight.
  • EXAMPLE 12
  • [0020]
    The wall provided by the above examples are semipermeable possessing a permeability to aqueous including biological fluids and impermeable to hydrocodone. The semipermeable walls comprise 15 mg to 200 mg of a cellulose polymer selected from the group consisting of a cellulose ester, cellulose diester, cellulose triester, cellulose ether, cellulose ester-ether, cellulose acylate, cellulose diacylate, cellulose triacylate, cellulose acetate, cellulose diacetate, and cellulose triacetate; the wall comprises 0 to 5 mg of a plasticizer represented by a member selected from the group consisting of trimethyl citrate, triethyl citrate, tributyl citrate, acetyltributyl citrate, acetyl tri-2-ethyl citrate, tributyl phosphate, triethyl phosphate, triphenyl citrate, tricyclohexyl citrate, and tricresyl citrate; the semipermeable wall comprises 2 mg to 50 mg of a poly(vinyl) polymer possessing a 10,000 to 200,000 molecular weight as represented by poly(vinyl pyrrolidone), copolymer of poly(vinyl-pyrrolidone and (vinyl acetate), copolymer of poly(vinyl pyrrolidone and vinyl alcohol), copolymer of poly(vinyl pyrrolidone and vinyl chloride), copolymer of poly(vinyl pyrrolidone and vinyl fluoride), copolymer of poly(vinyl pyrrolidone and vinyl butyrate), copolymer of poly(vinyl pyrrolidone and vinyl laurate),and copolymer of poly (vinyl pyrrolidone and vinyl stearate).
  • [0021]
    Exemplary solvents used for the present purpose comprise inorganic and organic solvents that do not adversely harm the materials and the final wall or the final compositions in the dosage form. The solvents broadly include members selected from the group consisting of aqueous solvents, alcohols, ketones, esters, ethers, aliphatic hydrocarbons, halogenated solvents, cycloaliphatics, aromatics, heterocyclic solvents, and mixtures thereof. Typical solvents include acetone, diacetone alcohol, methanol, ethanol, butyl alcohol, methyl acetate, ethyl acetate, isopropyl acetate, n-butyl acetate, methyl isobutyl ketone, methyl propyl ketone, n-hexane, n-heptane, ethylene glycol monoethyl ether, ethylene glycol monethyl acetate, methylene dichloride, ethylene dichloride, propylene dichloride, carbon tetrachloride, chloroform, nitroethane, nitropropane, tetrachloroethane, ethyl ether, isopropyl ether, cyclo-hexane, cyclo-octane, benzene, toluene, naphtha, 1,4-dioxane, tetrahydrofuran, diglyme, aqueous and nonaqueous mixtures thereof, such as acetone and water, acetone and methanol, acetone and ethyl alcohol, methylene dichloride and methanol, and ethylene dichloride and methanol.
  • [0022]
    Exit means, as used in the above examples for the dosage forms as used by this invention comprise means and methods suitable for the metered release of beneficial drug hydrocodone from the dosage form. The exit means comprises at least one passageway, orifice, or the like, through the wall for communicating with hydrocodone the dosage form. The expression, “at least one passageway,” comprises aperture, orifice, bore, pore, porous element through which the hydrocodone can migrate, hollow fiber, capillary tube, porous overlay, porous insert, and the like. The expression also includes a material that erodes or is leached from the wall in the fluid environment of use to produce least one passageway in the dosage form. Representative materials suitable for forming at least one passageway, or a multiplicity of passageways, include an erodible poly(glycolic) acid, or poly(lactic) acid member in the wall, a gelatinous filament, poly(vinyl alcohol), leachable materials such as fluid removable pore forming polysaccharides, salts, oxides, or the like. A passageway or a plurality of passageways can be formed by leaching a material such as sorbitol, lactose, fructose and the like from the wall. The passageway can have any shape such as round, triangular, square, elliptical, and the like, for assisting in the metered release of hydrocodone from the dosage form. The dosage form can be constructed with one or more passageways in spaced apart relations, or more than one passageway on a single surface of a dosage form. Passageways and equipment for forming passageways are disclosed in U.S. Pat. Nos. 3,845,770, 3,916,899; 4,063,064; and 4,088,864. Passageways of govern size formed by leaching are disclosed in U.S. Pat. Nos. 4,200,098 and 4,285,987.
  • EXAMPLE 13
  • [0023]
    A dosage form adapted, designed and shaped for the oral delivery of hydrocodone to a patient in need of hydrocodone therapy is manufactured as follows: first, 8.00 g of hydrocodone bitartrate hemipentahydrate, 5.50 g of sorbitol, 4.20 g of sodium carboxymethylcellulose possessing a 90,000 molecular weight and 1.00 g of hydroxypropylmethylcellulose of 9,200 molecular weight are screened separately through a 0.0165 inch (0.42 mm) 40 mesh screen. Next, the screened materials are blended on a three roll mill for 20 minutes to produce a homogenous blend. Then, a granulation is prepared by dissolving 1.20 g of poly(vinyl pyrrolidone) having a 40,000 molecular weight and 10 ml of denatured ethyl alcohol with constant stirring to provide a granulation fluid. Then, to all the ingredients on the milling machine, the granulation fluid is slowly added, and all the ingredients blended slowly for 5 minutes, to yield a wet granulation. The wetted mass is then passed through a 0.03331 inch (0.85 mm) 20 mesh screen and air dried at room temperature in a light current of moving air. After drying, the granulation is blended for an additional 2 minutes on a standard roll mill at 50% of its maximum speed. Then, {fraction (5/16)} inch (7.94 mm) round tablets, each comprising 150 mg of the hydrocodone composition are compressed on a Carver® press under a ¼-ton compression force to provide the first layer of a bilayer core. The hydrocodone composition comprises 60.00 mg of hydrocodone bitartrate hemipentahydrate, 41.25 mg of sorbitol, 31.50 mg of sodium carboxymethylcellulose possessing a 90,000 molecular weight 9.00 mg of poly(vinylpyrrolidone) possessing a 40,000 molecular weight, 7.50 mg of hydroxypropylmethylcellulose possessing a 9,200 molecular weight and 0.75 mg of magnesium stearate.
  • [0024]
    A composition for providing a push layer of a bilayer core arrangement is prepared comprising 44.06 mg of sodium carboxymethylcellulose possessing a 700,000 molecular weight, 22.50 mg of sodium chloride, 3.75 mg of hydroxypropylmethylcellulose possessing a 11,200 molecular weight, 0.75 mg of ferric oxide and 0.19 mg of magnesium stearate are used for preparing the push composition. A push granulation is prepared on a fluid bed granulator. A binder solution is made by dissolving hydroxypropylmethylcellulose in water. The binder solution is sprayed on the sodium carboxymethylcellulose 7H possessing a 700,000 molecular weight, the sodium chloride, hydroxypropylmethylcellulose and ferric oxide push-forming blend while the blend is fluidized and the granules are formed in the granulator. After the granulation is dried overnight at room temperature, the blend is remilled in a fluid air mill, and magnesium stearate is added to the mill.
  • [0025]
    The push-forming coposition is compressed into a {fraction (5/16)} inch (7.94 mm) round layer with each layer comprising 75 mg of the push composition using a Carver® press under a compression force of 1⅛-ton to provide the second layer of the bilayer core. The hydrocodone layer and the push layer are coated with a semipermeable wall-forming composition in a 12 inch (30 cm) coater. The semipermeable wall-forming composition comprises a 75:24:1, wt:wt:wt, mixture of cellulose acetate having a 39.8% acetyl content, poly(vinylpyrrolidone) having a 40,000 molecular weight, and triethyl citrate. The wall-forming components are dissolved in a 80:20, wt:wt, mixture of acetone and methanol at 4% solids. The average wet semipermeable wall weighted 36.8 mg. A single 25 mil (0.64 mm) passageway is drilled into each dosage form, and then the dosage forms are dried overnight at 40° celsius. The dosage form exhibited a mean release rate of 8.212 mg/hr over an extended 12 hours of therapy.
  • EXAMPLE 14
  • [0026]
    The procedure of the above example is followed for manufacturing a dosage form, characterized by a hydrocodone layer consisting of 0.5 to 1250 mg of hydrocodone, 10 to 50 mg of sorbitol, 10 to 50 mg of alkali carboxymethylcellulose of 70,000 to 400,000 molecular weight, 5 to 50 mg of hydroxypropylalkylcellulose of 9,000 to 150,000 molecular weight, 0 to 20 mg of poly(vinyl-pyrrolidone) of 10,000 to 140,000 molecular weight, and 0.01 to 5 mg of a lubricant; and a push composition comprising 10 to 60 mg of alkali carboxymethylcellulose of 650,000 to 1,200,000 molecular weight, which is a higher molecular weight then the molecular weight of the alkali carboxymethylcellulose present in the hydrocodone composition, 5 to 75 mg of osmagent, 1 to 30 mg of hydroxypropylmethylcellulose, 0 to 10 mg of ferric oxide, and 0 to 10 mg of lubricant.
  • DISCLOSURE FOR USING THE INVENTION
  • [0027]
    The invention concerns also a method for administering 0.5 mg to 1250 mg of hydrocodone to a patient in need of hydrocodone therapy. The method, in one administration comprises admitting orally into the patient 0.5 mg to 1250 mg of a hydrocodone selected from the group consisting of hydrocodone, and hydrocodone pharmaceutically acceptable salt, which is administered from a therapeutic composition comprising 0.5 mg to 1250 mg of hydrocodone, 10 mg to 350 mg of a poly(alkylene oxide) of 75,000 to 400,000 molecular weight, 5 mg to 50 mg of a hydroxyalkylcellulose of 9,000 to 150,000 molecular weight and 0.01 mg to 5 mg of a lubricant, which composition provides hydrocodone therapy over an extended period of time.
  • [0028]
    The invention concerns further a method for administering 0.5 mg to 1250 mg of hydrocodone by admitting orally 0.5 mg to 1250 mg of hydrocodone to a patient administered from a dosage form comprising a semipermeable wall permeable to aqueous and biological fluid and impermeable to the passage of hydrocodone, which semipermeable wall surrounds an internal compartment comprises a hydrocodone composition and a push composition. The hydrocodone composition consists of the composition above, and the push composition comprises 25 to 300 mg of a poly(alkylene oxide) of 3,000,000 to 7,500,000 molecular weight, 5 mg to 150 mg of an osmagent, 1 to 30 mg of a hydroxypropylmethylcellulose of 9,200 to 175,000 molecular weight, 0 to 10 mg of ferric oxide, 0 to 10 mg of lubricant and 0 to 3.5 mg of an antioxidant; and an exit means in the semipermeable wall for delivering the hydrocodone from the dosage form. The dosage form delivers the hydrocodone by imbibing fluid through the semipermeable wall into the dosage form causing the hydrocodone composition to change from a resting state to a dispensable state, and simultaneously causing the push composition to imbibe fluid, expand and push the hydrocodone composition through the exit, whereby through the combined operations of the dosage form the hydrocodone is delivered at a therapeutically effective dose at a controlled over an extended period of time.
  • [0029]
    Inasmuch as the foregoing specification comprises numerous embodiments, it is understood that variations and modifications can be made herein, in accordance with the principles disclosed, without departing from the invention.

Claims (19)

1. A therapeutic composition comprising 0.5 to 1250 mg of hydrocodone, 10 mg to 350 mg of a poly(alkylene oxide) possessing a 75,000 to 400,000 molecular weight, 5 mg to 50 of hydroxyalkylcellulose possessing a 9,000 to 150,000 molecular weight, and 0.01 mg to 5 mg of a lubricant.
2. The therapeutic composition according to claim 1, wherein the hydrocodone is selected from the group consisting of hydrocodone pharmaceutically acceptable salt, hydrocodone bitartrate hemipentahydrate, hydrocodone bitartrate, hydrocodone bitartrate hydrate, hydrocodone hydrochloride, hydrocodone phosphate, hydrocodone sulfate, hydrocodone mucate, hydrocodone sulfate pentahydrate and hydrocodone oleate.
3. The therapeutic composition according to claim 1, wherein the composition is compressed under 1⅛ to 10-ton force compression, and a semipermeable wall with an exit passageway encased the therapeutic composition.
4. A therapeutic composition comprising 0.5 to 1250 mg of hydrocodone, 10 to 50 mg of alkali carboxymethylcellulose of 70,000 to 400,000 molecular weight, 5 to 50 mg of hydroxypropylalkylcellulose of 9,000 to 150,000 molecular weight, and 0.01 to 5 mg of a lubricant.
5. The therapeutic composition according to claim 4, wherein the therapeutic composition comprises poly(vinylpyrrolidone).
6. The therapeutic composition according to claim 4, wherein the therapeutic composition comprises sorbitol.
7. The therapeutic composition according to claim 4, wherein the hydrocodone is selected from the group consisting of hydrocodone bitartrate hemipentahydrate, hydrocodone bitartrate, hydrocodone hydrochloride, hydrocodone phosphate and hydrocodone sulfate.
8. The therapeutic composition according to claim 4, wherein a semipermeable wall with an exit passageway surrounds the therapeutic composition.
9. A bilayer composition comprising a hydrocodone layer comprising 0.5 to 1250 mg of hydrocodone, 10 mg to 350 mg of a poly(alkylene oxide) of 75,000 to 400,000 molecular weight, 5 to 50 mg of a hydroxyalkylcellulose of 9,000 to 450,000 molecular weight and 0.01 to 5 mg of a lubricant; and a push layer comprising 25 to 300 mg of a poly(alkylene oxide) of 3,000,000 to 7,500,000 molecular weight, 5 to 150 mg of an osmagent, and 1 to 30 mg of a hydroxypropylalkylcellulose of 9,200 to 175,000 molecular weight.
10. The bilayer composition according to claim 4, wherein the push composition comprises an antioxidant.
11. The bilayer composition according to claim 4, wherein the push composition comprises a lubricant.
12. The bilayer composition according to claim 4, wherein a semipermeable wall with an exit passageway surrounds the bilayer composition.
13. A bilayer composition comprising a hydrocodone layer comprising 0.5 to 1250 mg of hydrocodone, 10 to 50 mg of alkli carboxymethylcellulose comprising a 70,000 to 400,000 molecular weight, 5 to 50 mg of hydroxypropylalkylcellulose of 9,000 to 150,000 molecular weight; and a push layer comprising 10 to 60 mg of an alkali carboxymethylcellulose of 650,000 to 1,200,000 molecular weight, 5 to 75 mg of an osmagent, and 1 to 30 mg of a hydroxypropylalkylcellulose of 9,000 to 150,000 molecular weight.
14. The bilayer composition according to claim 13 wherein the hydrocodone layer comprises a poly(vinylpyrrolidone).
15. The bilayer composition according to claim 13, wherein a semipermeable wall comprising a passageway surrounds the bilayer composition.
16. A method for administering 0.5 to 1250 mg of hydrocodone to a patient in need of hydrocodone therapy, which method comprises admitting orally into the gastrointestinal tract of the patient a sustained delivery composition comprising the hydrocodone, and a polymer carrier for the hydrocodone comprising a 75,000 to 400,000 molecular weight that is delivered at a rate of release of 0.5 mg to 10 mg per hour over a sustained period of 20 hours.
17. The method for administering the hydrocodone according to claim 16, wherein the hydrocodone composition is surrounded by a semipermeable wall permeable to the passage fluid in the gastrointestinal tract and impermeable to the passage of hydrocodone, with a passageway in the semipermeable wall for delivering the hydrocodone to the patient.
18. A method for administering 0.5 to 1250 mg of hydrocodone to a patient in need of hydrocodone therapy, which method comprises orally administering the hydrocodone at a rate of 0.5 mg to 10 mg per hour over 20 hours, for hydrocodone therapy.
19. A method for administering 0.5 to 1250 mg of hydrocodone to a patient in need of hydrocodone therapy, which method comprises orally admitting into the gastrointestinal tract of the patient a bilayer comprising a hydrocodone layer comprising 0.5 to 1250 mg of hydrocodone, 10 mg to 350 mg of poly(alkylene oxide) possessing a 75,000 to 400,000 molecular weight, 5 to 50 mg of a hydroxyalkylcellulose of 9,000 to 450,000 molecular weight and 0.01 to 5 mg of a lubricant; and a push layer comprising 25 mg to 300 mg of a poly(alkylene oxide) of 3,000 to 7,500,000 molecular weight 5 to 150 mg an osmagent, and 1 to 30 mg of a hydroxypropylalkylcellulose of 9,200 to 175,000 molecular weight, which bilayer delivers the hydrocodone over a period of 30 hours to the gastrointestinal tract of the patient.
US10267500 1994-09-16 2002-12-18 Hydrocodone therapy Abandoned US20030077320A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US08277399 US6491945B1 (en) 1994-09-16 1994-09-16 Hydrocodone therapy
US10267500 US20030077320A1 (en) 1994-09-16 2002-12-18 Hydrocodone therapy

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US10267500 US20030077320A1 (en) 1994-09-16 2002-12-18 Hydrocodone therapy

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US08277399 Continuation US6491945B1 (en) 1994-09-16 1994-09-16 Hydrocodone therapy

Publications (1)

Publication Number Publication Date
US20030077320A1 true true US20030077320A1 (en) 2003-04-24

Family

ID=23060700

Family Applications (3)

Application Number Title Priority Date Filing Date
US08277399 Active US6491945B1 (en) 1994-09-16 1994-09-16 Hydrocodone therapy
US08680399 Expired - Lifetime US5866161A (en) 1994-09-16 1996-07-15 Hydrocodone therapy
US10267500 Abandoned US20030077320A1 (en) 1994-09-16 2002-12-18 Hydrocodone therapy

Family Applications Before (2)

Application Number Title Priority Date Filing Date
US08277399 Active US6491945B1 (en) 1994-09-16 1994-09-16 Hydrocodone therapy
US08680399 Expired - Lifetime US5866161A (en) 1994-09-16 1996-07-15 Hydrocodone therapy

Country Status (2)

Country Link
US (3) US6491945B1 (en)
WO (1) WO1996008253A1 (en)

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050089570A1 (en) * 2003-09-26 2005-04-28 Evangeline Cruz Oros push-stick for controlled delivery of active agents
US20050112195A1 (en) * 2003-09-26 2005-05-26 Evangeline Cruz Drug coating providing high drug loading and methods for providing same
US20050158382A1 (en) * 2003-09-26 2005-07-21 Evangeline Cruz Controlled release formulations of opioid and nonopioid analgesics
US20070281018A1 (en) * 2004-09-24 2007-12-06 Abbott Laboratories Sustained release formulations of opioid and nonopioid analgesics
US20090022798A1 (en) * 2007-07-20 2009-01-22 Abbott Gmbh & Co. Kg Formulations of nonopioid and confined opioid analgesics
US20090317355A1 (en) * 2006-01-21 2009-12-24 Abbott Gmbh & Co. Kg, Abuse resistant melt extruded formulation having reduced alcohol interaction
US20100172989A1 (en) * 2006-01-21 2010-07-08 Abbott Laboratories Abuse resistant melt extruded formulation having reduced alcohol interaction
US8808745B2 (en) 2001-09-21 2014-08-19 Egalet Ltd. Morphine polymer release system
US8877241B2 (en) 2003-03-26 2014-11-04 Egalet Ltd. Morphine controlled release system
US9005660B2 (en) 2009-02-06 2015-04-14 Egalet Ltd. Immediate release composition resistant to abuse by intake of alcohol
US9023394B2 (en) 2009-06-24 2015-05-05 Egalet Ltd. Formulations and methods for the controlled release of active drug substances
US9044402B2 (en) 2012-07-06 2015-06-02 Egalet Ltd. Abuse-deterrent pharmaceutical compositions for controlled release
US9132096B1 (en) 2014-09-12 2015-09-15 Alkermes Pharma Ireland Limited Abuse resistant pharmaceutical compositions
US9226907B2 (en) 2008-02-01 2016-01-05 Abbvie Inc. Extended release hydrocodone acetaminophen and related methods and uses thereof
US9642809B2 (en) 2007-06-04 2017-05-09 Egalet Ltd. Controlled release pharmaceutical compositions for prolonged effect
US9694080B2 (en) 2001-09-21 2017-07-04 Egalet Ltd. Polymer release system
US9884029B2 (en) 2003-03-26 2018-02-06 Egalet Ltd. Morphine controlled release system

Families Citing this family (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6491945B1 (en) * 1994-09-16 2002-12-10 Alza Corporation Hydrocodone therapy
JPH1050306A (en) * 1996-07-31 1998-02-20 Toyota Autom Loom Works Ltd Manufacture of hydrogen storage alloy electrode
US8524277B2 (en) * 1998-03-06 2013-09-03 Alza Corporation Extended release dosage form
RU2230556C2 (en) * 1999-10-29 2004-06-20 Эро-Селтик, С.А. Hydrocodon preparative sustained-release formulations
JP2004512354A (en) * 2000-10-30 2004-04-22 ユーロ−セルティーク,エス.エイ. Hydrocodone controlled-release formulation
US8557291B2 (en) * 2002-07-05 2013-10-15 Collegium Pharmaceutical, Inc. Abuse-deterrent pharmaceutical compositions of opioids and other drugs
US8840928B2 (en) 2002-07-05 2014-09-23 Collegium Pharmaceutical, Inc. Tamper-resistant pharmaceutical compositions of opioids and other drugs
KR20050095835A (en) * 2003-01-14 2005-10-04 알자 코포레이션 Methods and dosage forms with modified viscosity layers
EP1765292B1 (en) 2004-06-12 2017-10-04 Collegium Pharmaceutical, Inc. Abuse-deterrent drug formulations
US20080274183A1 (en) * 2005-02-04 2008-11-06 Phillip Michael Cook Thermoplastic articles containing a medicament
EP2292229B1 (en) 2006-08-25 2012-05-23 Purdue Pharma LP Tamper resistant oral pharmaceutical dosage forms comprising an opioid analgesic
JP2010522135A (en) 2006-10-09 2010-07-01 チャールストン ラボラトリーズ,インコーポレイテッド Pharmaceutical compositions
WO2009023672A3 (en) * 2007-08-13 2009-12-30 Abuse Deterrent Pharmaceutical Llc Abuse resistant drugs, method of use and method of making
US8124126B2 (en) 2008-01-09 2012-02-28 Charleston Laboratories, Inc. Pharmaceutical compositions
WO2009114648A1 (en) 2008-03-11 2009-09-17 Depomed Inc. Gastric retentive extended-release dosage forms comprising combinations of a non-opioid analgesic and an opioid analgesic
US8372432B2 (en) 2008-03-11 2013-02-12 Depomed, Inc. Gastric retentive extended-release dosage forms comprising combinations of a non-opioid analgesic and an opioid analgesic
EP2451274B1 (en) 2009-07-08 2017-10-04 Charleston Laboratories, Inc. Pharmaceutical compositions
CN102596252A (en) * 2009-08-31 2012-07-18 蒂宝制药公司 Gastric retentive pharmaceutical compositions for immediate and extended release of acetaminophen
US8597681B2 (en) 2009-12-22 2013-12-03 Mallinckrodt Llc Methods of producing stabilized solid dosage pharmaceutical compositions containing morphinans
US9198861B2 (en) 2009-12-22 2015-12-01 Mallinckrodt Llc Methods of producing stabilized solid dosage pharmaceutical compositions containing morphinans
ES2643291T3 (en) 2010-12-22 2017-11-22 Purdue Pharma L.P. Forms of controlled release dosage with tamper proof coated
US8658631B1 (en) 2011-05-17 2014-02-25 Mallinckrodt Llc Combination composition comprising oxycodone and acetaminophen for rapid onset and extended duration of analgesia
US8741885B1 (en) 2011-05-17 2014-06-03 Mallinckrodt Llc Gastric retentive extended release pharmaceutical compositions
US8858963B1 (en) 2011-05-17 2014-10-14 Mallinckrodt Llc Tamper resistant composition comprising hydrocodone and acetaminophen for rapid onset and extended duration of analgesia
US20130143867A1 (en) 2011-12-02 2013-06-06 Sychroneuron Inc. Acamprosate formulations, methods of using the same, and combinations comprising the same
WO2017222575A1 (en) 2016-06-23 2017-12-28 Collegium Pharmaceutical, Inc. Process of making more stable abuse-deterrent oral formulations

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3845770A (en) * 1972-06-05 1974-11-05 Alza Corp Osmatic dispensing device for releasing beneficial agent
US3916899A (en) * 1973-04-25 1975-11-04 Alza Corp Osmotic dispensing device with maximum and minimum sizes for the passageway
US4111201A (en) * 1976-11-22 1978-09-05 Alza Corporation Osmotic system for delivering selected beneficial agents having varying degrees of solubility
US4111202A (en) * 1976-11-22 1978-09-05 Alza Corporation Osmotic system for the controlled and delivery of agent over time
US4327725A (en) * 1980-11-25 1982-05-04 Alza Corporation Osmotic device with hydrogel driving member
US4464378A (en) * 1981-04-28 1984-08-07 University Of Kentucky Research Foundation Method of administering narcotic antagonists and analgesics and novel dosage forms containing same
US4576604A (en) * 1983-03-04 1986-03-18 Alza Corporation Osmotic system with instant drug availability
US4612008A (en) * 1983-05-11 1986-09-16 Alza Corporation Osmotic device with dual thermodynamic activity
US5021053A (en) * 1989-07-14 1991-06-04 Alza Corporation Oral osmotic device with hydrogel driving member
US5190765A (en) * 1991-06-27 1993-03-02 Alza Corporation Therapy delayed
US5866161A (en) * 1994-09-16 1999-02-02 Alza Corporation Hydrocodone therapy

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4847077A (en) * 1984-07-18 1989-07-11 Pennwalt Corporation Controlled release pharmaceutical preparations
GB8521350D0 (en) * 1985-08-28 1985-10-02 Euro Celtique Sa Analgesic composition
US4996047A (en) * 1988-11-02 1991-02-26 Richardson-Vicks, Inc. Sustained release drug-resin complexes
CA2007181C (en) * 1989-01-06 1998-11-24 Angelo Mario Morella Sustained release pharmaceutical composition
US5518730A (en) * 1992-06-03 1996-05-21 Fuisz Technologies Ltd. Biodegradable controlled release flash flow melt-spun delivery system

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3845770A (en) * 1972-06-05 1974-11-05 Alza Corp Osmatic dispensing device for releasing beneficial agent
US3916899A (en) * 1973-04-25 1975-11-04 Alza Corp Osmotic dispensing device with maximum and minimum sizes for the passageway
US4111201A (en) * 1976-11-22 1978-09-05 Alza Corporation Osmotic system for delivering selected beneficial agents having varying degrees of solubility
US4111202A (en) * 1976-11-22 1978-09-05 Alza Corporation Osmotic system for the controlled and delivery of agent over time
US4327725A (en) * 1980-11-25 1982-05-04 Alza Corporation Osmotic device with hydrogel driving member
US4464378A (en) * 1981-04-28 1984-08-07 University Of Kentucky Research Foundation Method of administering narcotic antagonists and analgesics and novel dosage forms containing same
US4576604A (en) * 1983-03-04 1986-03-18 Alza Corporation Osmotic system with instant drug availability
US4612008A (en) * 1983-05-11 1986-09-16 Alza Corporation Osmotic device with dual thermodynamic activity
US5021053A (en) * 1989-07-14 1991-06-04 Alza Corporation Oral osmotic device with hydrogel driving member
US5190765A (en) * 1991-06-27 1993-03-02 Alza Corporation Therapy delayed
US5866161A (en) * 1994-09-16 1999-02-02 Alza Corporation Hydrocodone therapy

Cited By (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8808745B2 (en) 2001-09-21 2014-08-19 Egalet Ltd. Morphine polymer release system
US9707179B2 (en) 2001-09-21 2017-07-18 Egalet Ltd. Opioid polymer release system
US9694080B2 (en) 2001-09-21 2017-07-04 Egalet Ltd. Polymer release system
US9884029B2 (en) 2003-03-26 2018-02-06 Egalet Ltd. Morphine controlled release system
US9375428B2 (en) 2003-03-26 2016-06-28 Egalet Ltd. Morphine controlled release system
US8877241B2 (en) 2003-03-26 2014-11-04 Egalet Ltd. Morphine controlled release system
US20050158382A1 (en) * 2003-09-26 2005-07-21 Evangeline Cruz Controlled release formulations of opioid and nonopioid analgesics
US20060251721A1 (en) * 2003-09-26 2006-11-09 Evangeline Cruz Controlled release formulations of opioid and nonopioid analgesics
US20050112195A1 (en) * 2003-09-26 2005-05-26 Evangeline Cruz Drug coating providing high drug loading and methods for providing same
US8226979B2 (en) 2003-09-26 2012-07-24 Alza Corporation Drug coating providing high drug loading and methods for providing the same
US8246986B2 (en) 2003-09-26 2012-08-21 Alza Corporation Drug coating providing high drug loading
US20050089570A1 (en) * 2003-09-26 2005-04-28 Evangeline Cruz Oros push-stick for controlled delivery of active agents
US8541026B2 (en) 2004-09-24 2013-09-24 Abbvie Inc. Sustained release formulations of opioid and nonopioid analgesics
US20070281018A1 (en) * 2004-09-24 2007-12-06 Abbott Laboratories Sustained release formulations of opioid and nonopioid analgesics
US20100172989A1 (en) * 2006-01-21 2010-07-08 Abbott Laboratories Abuse resistant melt extruded formulation having reduced alcohol interaction
US20090317355A1 (en) * 2006-01-21 2009-12-24 Abbott Gmbh & Co. Kg, Abuse resistant melt extruded formulation having reduced alcohol interaction
US9642809B2 (en) 2007-06-04 2017-05-09 Egalet Ltd. Controlled release pharmaceutical compositions for prolonged effect
US20090022798A1 (en) * 2007-07-20 2009-01-22 Abbott Gmbh & Co. Kg Formulations of nonopioid and confined opioid analgesics
US9226907B2 (en) 2008-02-01 2016-01-05 Abbvie Inc. Extended release hydrocodone acetaminophen and related methods and uses thereof
US9358295B2 (en) 2009-02-06 2016-06-07 Egalet Ltd. Immediate release composition resistant to abuse by intake of alcohol
US9005660B2 (en) 2009-02-06 2015-04-14 Egalet Ltd. Immediate release composition resistant to abuse by intake of alcohol
US9023394B2 (en) 2009-06-24 2015-05-05 Egalet Ltd. Formulations and methods for the controlled release of active drug substances
US9044402B2 (en) 2012-07-06 2015-06-02 Egalet Ltd. Abuse-deterrent pharmaceutical compositions for controlled release
US9486451B2 (en) 2014-09-12 2016-11-08 Recro Gainesville Llc Abuse resistant pharmaceutical compositions
US9132096B1 (en) 2014-09-12 2015-09-15 Alkermes Pharma Ireland Limited Abuse resistant pharmaceutical compositions
US9713611B2 (en) 2014-09-12 2017-07-25 Recro Gainesville, LLC Abuse resistant pharmaceutical compositions
US9452163B2 (en) 2014-09-12 2016-09-27 Recro Gainesville Llc Abuse resistant pharmaceutical compositions

Also Published As

Publication number Publication date Type
US5866161A (en) 1999-02-02 grant
WO1996008253A1 (en) 1996-03-21 application
US6491945B1 (en) 2002-12-10 grant

Similar Documents

Publication Publication Date Title
US3538214A (en) Controlled release medicinal tablets
US4624847A (en) Drug delivery device for programmed delivery of beneficial drug
US7846476B2 (en) Once-a-day oxycodone formulations
US6764697B1 (en) System for delaying drug delivery up to seven hours
US5098714A (en) Osmotic, oral dosage form for fertility control
US8142811B2 (en) Controlled release hydrocodone formulations
US5147654A (en) Oral osmotic device for delivering nicotine
US5736159A (en) Controlled release formulation for water insoluble drugs in which a passageway is formed in situ
US5200197A (en) Contraceptive pill
US6605302B2 (en) Drug delivery device containing oseltamivir and an H1 antagonist
US6245357B1 (en) Extended release dosage form
US5955103A (en) Dosage form comprising antiepileptic drug
US5912268A (en) Dosage form and method for treating incontinence
US4892739A (en) Osmotic continuous dispensing oral delivery system containing a pharmaceutically acceptable active agent having a improved core membrane adhesion properties
US4816264A (en) Sustained release formulations
US20100221293A1 (en) Controlled release formulations of opioid and nonopioid analgesics
US6500459B1 (en) Controlled onset and sustained release dosage forms and the preparation thereof
US20050191349A1 (en) Galantamine formulations
US6036973A (en) Therapy for neurological diseases
US4609374A (en) Osmotic device comprising means for governing initial time of agent release therefrom
US20110053866A1 (en) Pharmaceutical compositions
US20050208132A1 (en) Methods and dosage forms for reducing side effects of benzisozazole derivatives
US20030224051A1 (en) Dosage forms and compositions for osmotic delivery of variable dosages of oxycodone
US20050152974A1 (en) Atomoxetine formulations
US4454108A (en) Prolonged-action multiple-layer tablets

Legal Events

Date Code Title Description
AS Assignment

Owner name: BANK OF AMERICA, N.A., NORTH CAROLINA

Free format text: SECURITY INTEREST;ASSIGNOR:REMINGTON CORPORATION, L.L.C.;REEL/FRAME:014805/0733

Effective date: 20030930