Morphine therapy

• US 5,460,826 A
• Filed: 06/27/1994
• Issued: 10/24/1995
• Est. Priority Date: 06/27/1994
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Hwang, Paul, Ayer, Atul D., Kuczynski, Anthony L., Merrill, Sonya
• Primary Examiner(s): KISHORE, GOLLAMUDI S
• Application Number:
  US08/266,075
• Time in Patent Office: 484 Days
• Field of Search: 424/457-461, 424/464, 424/465, 424/468, 424/474, 424/469, 424/470, 424/472, 424/473
• US Class Current: 424/470
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids

Abstract

A bilayer comprising a morphine layer of morphine, poly(alkylene oxide) and poly(vinylpyrrolidone); and an expandable contacting layer of coated granules of a higher molecular weight poly(alkylene oxide) and a hydroxyalkylcellulose, which bilayer is disclosed for morphine therapy. A method is disclosed for using the bilayer composition.

Claims

1. A dosage in the form of a tablet comprising:

a morphine composition layer comprising 10 wt % to 98 wt % of morphine, 10 wt % of 80 wt % of a poly(alkylene oxide) having a 100,000 to 650,000 molecular weight, and 1 wt % to 20 wt % of a poly(vinyl pyrrolidone) having a 3,000 to 350,000 molecular weight;

an expandable layer comprising granules coated with hydroxypropylmethylcellulose, said granules comprising 40 wt % to 99 wt % of poly(alkylene oxide) having a 3,000,000 to 7,500,000 molecular weight, 0 wt % to 80 wt % of an osmagent, and 0.25 wt % to 25 wt % of hydroxyalkylcellulose having a 7,500 to 75,000 molecular weight.

2. The dosage form according to claim 1, wherein morphine is a member selected from the group consisting of morphine base, morphine chlorhydrate, morphine bitartrate, morphine bi(trifluoroacetate), morphine bi(pentafluoropropionate), morphine bi(methylcarbonate), morphine bi(heptafluorbutyrate), morphine phosphate monobasic, morphine acetate, morphine n-oxide, morphine sulfate, morphine n-oxide, morphine oleate, morphine methylbiomide, morphine mutate, morphine hydrochloride, and morphine hydrobiomide.

3. A method for administering 50 ng to 1,200 mg of morphine to a human, which method comprises admitting orally into the gastrointestinal tract of the human 50 ng to 1,200 mg of morphine that is administered from a dosage in the form of a tablet comprising a morphine layer comprising 10 wt % to 98 wt % of morphine, 10 wt % to 80 wt % of poly(alkylene oxide) having a 100,000 to 650,000 molecular weight and 1 wt % to 20 wt % of poly(vinyl pyrrolidone) having a 3,000 to 350,000 molecular weight, a hydrogel layer comprising coated granules comprising 40 wt % to 99 wt % of poly(alkylene oxide) having 3,000,000 to 7,500,000 molecular weight, and 0 wt % to 80 wt % of an osmagent, said coat comprising 0.25 wt % to 25 wt % of a hydroxyalkylcellulose possessing a 7,500 to 75,000 molecular weight, and a semipermeable cellulose acetate polymeric composition surrounding the morphine layer and the hydrogel layer.