Pharmaceutical tablet capable of liberating one or more drugs at different release rates

• US 5,738,874 A
• Filed: 03/24/1995
• Issued: 04/14/1998
• Est. Priority Date: 09/24/1992
• Status: Expired due to Term

• Current Assignee: Jagotec Ag (Vectura Group Ltd.)
• Original Assignee: Jagotec Ag (Vectura Group Ltd.)
• Inventors: La Manna, Aldo, Maggi, Lauretta, Conte, Ubaldo
• Primary Examiner(s): Page, Thurman L.
• Assistant Examiner(s): Spear, James M.
• Application Number:
  US08/406,873
• Time in Patent Office: 1,117 Days
• Field of Search: 424/464, 424/472, 424/480, 424/482, 424/468, 424/479, 424/481
• US Class Current: 424/472
• CPC Class Codes: A61K 9/2072 characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms A61K9/0004, A61K9/0056, A61K9/0065 take precedence
• CPC Class Codes: A61K 9/2086 Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• 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: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Pharmaceutical tablet consisting of a first layer containing one or more drugs with immediate or controlled release formulation, a second layer containing one or more drugs, either equal to or different from the first layer, with slow release formulation, and a low-permeability barrier-type layer coating said second layer or, alternatively, placed between the first and second layer and, if necessary, containing a drug.

Claims

1. Pharmaceutical compressed tablet capable of releasing one or more drugs at two different steps, consisting of three layers of discoidal shape, obtained by compression of the mixture of the granular components and wherein:

a first layer, which carries out a first release step, contains one or more drugs with immediate or controlled release formulation, comprising polymeric substances which swell or solubilize when contacted with aqueous liquids, said polymeric substances selected from the group consisting of cross-linked polyvinylpyrrolidone, low and medium molecular weight hydroxypropyl cellulose and hydroxypropyl methylcellulose, cross-linked sodium carboxymethylcellulose, carboxymethyl starch, potassium methacrylate-divinylbenzene copolymer, polyvinyl alcohols, starches, microcrystalline cellulose and β

-cyclodextrin, said polymeric substances amounting to from about 1% to about 90% by weight of said first layer;

a second layer adjacent to the first layer and carrying out a second release step, contains one or more drugs, either equal to or different from those of the first layer with slow release formulation, comprising polymeric substances which swell or erode or are gellable when contacted with aqueous liquids said polymeric substances selected from the group consisting of hydroxypropyl methylcellulose having a molecular weight from 1000 to 4,000,000, hydroxypropyl cellulose having molecular weight from 2,000 to 2,000,000, carboxyvinyl polymers, polyvinyl alcohols, glucans, scleroglucans, mannans, xanthans, alginic acid, and carboxymethylcellulose, said polymeric substances amounting to from about 5% to about 90% by weight of said second layer; and

a third barrier layer having low permeability and coating the free surface of said second layer and comprising polymeric substances selected from the group consisting of hydroxypropyl methylcellulose having a molecular weight from 1,000 to 4,000,000, hydroxypropyl cellulose having molecular weight from 2,000 to 2,000,000, glucans, scleroglucans, mannans, xanthans, carboxymethylcellulose, ethylcellulose, and methylcellulose said polymeric substances amounting to from about 5% to about 90% by weight of said third layer.

2. The compressed tablet according to claim 1 wherein barrier layer coats partially the second layer, the remaining surface of second layer being covered by first layer.

3. The compressed tablet according to claim 1, wherein said first layer is 0.5 to 5 mm thick.

4. The compressed tablet according to claim 1, wherein said second layer is 0.5 to 5 mm thick.

5. The compressed tablet according to claim 1, wherein said barrier layer is 0.1 to 4.5 mm thick.

6. The compressed tablet according to claim 1, wherein said drugs are selected from the group consisting of diclofenac sodium, indomethacin, ibuprofen, ketoprofen, diflunisal, piroxicam, naproxen, flurbiprofen, tolmentin sodium, ampicillin, amoxycillin, cephradine, clavulanic acid, cephachlor, cephalexin, cloxacillin, erythromycin, their salts nitrofurantoin, nalidixic acid, oxolinic acid, pipemidic acid diazepam, nitrazepam, flurazepam, oxazepam, chlordiazepoxide, medazepam, lorazepam, diltiazem, trapidil, urapidil, benziodarone, dipiridamole, lidoflazine, naphthydrofuryl oxalate, perhexeline maleate, oxyfedrine hydrochloride, ephedrine, terfenadine, theophylline, L-dopa, carbidopa and chlorpheniramine.

7. The compressed tablet of claim 1 wherein said polymeric substances of said second layer may be further selected from the group consisting of poly(methyl vinyl ethers/maleic anhydride), ethylcellulose and methylcellulose.