Method of producing multi-layer medicaments in solid form for oral or rectal administration

• US 6,120,802 A
• Filed: 04/15/1998
• Issued: 09/19/2000
• Est. Priority Date: 10/23/1995
• Status: Expired due to Term

• Current Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated)
• Original Assignee: BASF AG (BASF SE)
• Inventors: Hartl, Axel Paul, Breitenbach, Jorg, Hofmann, Jurgen, Rosenberg, Joerg, Schiessl, Michael, Zettler, Hans Dieter
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): HOWARD, SHARON LEE
• Application Number:
  US09/051,544
• Time in Patent Office: 888 Days
• Field of Search: 424/464, 424/465, 424/474, 514/966
• US Class Current: 424/464
• CPC Class Codes: A61J 2200/20 Extrusion means, e.g. for producing pharmaceutical forms
• CPC Class Codes: A61J 3/10 into the form of compressed tablets tablet presses B30B11/00
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/07 Retinol compounds, e.g. vitamin A retinoic acids A61K31/203
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/277 having a ring, e.g. verapamil
• CPC Class Codes: A61K 31/355 Tocopherols, e.g. vitamin E
• CPC Class Codes: A61K 31/375 Ascorbic acid, i.e. vitamin C; Salts thereof
• CPC Class Codes: A61K 31/401 Proline; Derivatives thereof, e.g. captopril
• CPC Class Codes: A61K 31/4422 1,4-Dihydropyridines, e.g. nifedipine, nicardipine
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/616 by carboxylic acids, e.g. acetylsalicylic acid
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61K 9/2893 Tablet coating processes mechanical aspects A61J3/06
• CPC Class Codes: B30B 11/14 co-operating with moulds on a movable carrier other than a turntable or a rotating drum
• CPC Class Codes: B30B 11/16 using pocketed rollers, e.g. two co-operating pocketed rollers
• CPC Class Codes: B30B 11/18 : using profiled rollers
• CPC Class Codes: B30B 11/34 : for coating articles, e.g. tablets
• CPC Class Codes: B30B 15/308 : in a continuous manner, e.g. for roller presses, screw extrusion presses

Abstract

The present invention relates to a process for producing multilayer, solid drug forms for oral or rectal administration, which comprises coextrusion of at least two compositions which in each case comprise a thermoplastic, pharmacologically acceptable polymeric binder which is soluble or swellable in a physiological environment, and at least one of which contains a pharmaceutical active ingredient, and shaping the coextruded multilayer material to the required drug form.

Claims

1. A process for producing multilayer, solid drug forms for oral or rectal administration, which comprises coextrusion of at least two compositions which in each case comprise a thermoplastic, pharmacologically acceptable polymeric binder which is soluble or swellable in a physiological environment, and at least one of which contains a pharmaceutical active ingredient, and shaping the coextruded multilayer material to the required drug form.

2. A process as claimed in claim 1, wherein the polymeric binder for a layer containing no active ingredient is selected from the group consisting of hydroxyalkylcelluloses, alkylcelluloses, hydroxyalkylalkylcelluloses, cellulose phthalates, polyacrylates, galactomannans and polylactides.

3. A process as claimed in claim 1, wherein the polymeric binder for a layer containing active ingredient is selected from the group consisting of polyvinylpyrrolidones, copolymers of N-vinylpyrrolidone and vinyl esters and hydroxyalkyl acrylates.

4. A process as claimed in claim 1, wherein an active ingredient which is selected from the group consisting of ibuprofen, ketoprofen, flurbiprofen, acetylsalicylic acid, verapamil, paracetamol, nifedipine, caffeine, captopril and vitamins or mixtures of two or more of these active ingredients is used.

5. A process as claimed claim 1, wherein to produce closed drug forms the coextrusion is carried out with a concentric annular coextrusion die and the shaping is carried out in a molding calender or by a hot or cold cut method.

6. A process as claimed in claim 1, wherein to produce open drug forms, especially open multilayer tablets, the coextrusion is carried out using a slot die and the shaping is carried out by punching.

7. A process as claimed in claim 5, wherein hydroxypropylcellulose is used as polymeric binder for the outer layer(s), and polyvinylpyrrolidone is used for the inner layer and the core.

8. A process as claimed in claim 5, wherein ibuprofen alone or ibuprofen/caffeine or vitamins A, C, E are used as active ingredient, with the ibuprofen or the vitamins A and E being located in the core and the caffeine or the vitamin C being located in the outer layer.

9. A process as claimed in claim 1, wherein the multilayer drug forms are, in a subsequent step, rounded and/or provided with a coating.

10. A multilayer solid drug form for oral or rectal administration obtainable by a process as claimed in claim 1.