Multiple unit controlled food effect-independent release pharmaceutical preparations and method for preparing the same

• US 6,805,881 B1
• Filed: 04/23/2001
• Issued: 10/19/2004
• Est. Priority Date: 09/18/1998
• Status: Expired due to Fees

• Current Assignee: Bayer Schering Pharma AG (Bayer AG)
• Original Assignee: Bayer AG
• Inventors: Rupp, Roland, Weisemann, Claus, Chantraine, Ernst, Brendel, Erich, Kanikanti, Venkata-Rangarao
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Sheikh, Humera N.
• Application Number:
  US09/787,229
• Time in Patent Office: 1,275 Days
• Field of Search: 424/488, 424/457, 424/458, 424/464, 424/468, 424/474, 424/451, 414/451
• US Class Current: 424/488
• CPC Class Codes: A61K 31/4422 1,4-Dihydropyridines, e.g. nifedipine, nicardipine
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The present invention relates to orally administrable multiple-unit sustained-release dose forms having controlled agitation-independent release of active compound and processes for their production using a selected erodable hydrophilic polymer (HPC) and a limitation of the maximum size of the active compound-containing polymer particles to ≦3 mm.

Claims

1. A process for the production of an orally administratable multiple-unit sustained-release pharmaceutical composition having controlled agitation-independent release, consisting essentially of the steps of (a) combining hydroxypropylcellulose polymer having a molecular weight of 250000 to 1200000 and a molar degree of substitution of at least 3 in an amount from 40 to 95% by weight with a pharmaceutically active compound and optionally with one or more pharmaceutically acceptable additional polymers and/or excipients which do not contribute significantly to a sustained-release effect, to obtain a mixture of containing said hydroxypropyl cellulose polymer and said active compound;

(b) converting said mixture into particles having a diameter of 0.2 to 3.0 mm;

(c) optionally lacquering said particles, and (d) incorporating said particles into an orally administratable multi-unit sustained release dosage form.

2. The process according to claim 1, wherein said hydroxypropylcellulose polymer is employed in an amount from 45 to 90% by weight.

3. The process according to claim 1, wherein said hydroxypropylcellulose polymer has an average molecular weight of 350000 to 1150000.

4. The process according to claim 1, wherein said particles have a maximum diameter of 0.5 to 2 mm.

5. The process according to claim 1, wherein said particles are produced by melt extrusion and/or granulation.

6. The process according to claim 1, wherein said particles are converted into said orally administratable pharmaceutical composition by conventional tableting methods.

7. The process according to claim 1, wherein said particles are in the form of pellets, granules, minitablets or grains.

11. The process according to claim 1 wherein said orally administratable multi-unit sustained release dosage form is a capsule, a sachet, or a tablet which decomposes into its constituent particles quickly after being administered.

12. The process of claim 11 wherein said dosage form is a capsule.

8. A pharmaceutical composition consisting essentially of a mixture of hydroxypropylcellulose polymer and a pharmaceutically active compound and optionally one or more pharmaceutically acceptable additional polymers and/or excipients which do not contribute significantly to a sustained-release effect, wherein said hydroxypropylcellulose polymer has a molecular weight of between 250,000 and 1,200,000 and a molar degree of substitution of ≧

3 and is 40-95% by weight of said mixture and further wherein said mixture is granulated to particles having a diameter of between 0.2 and 3.0 mm, said particles being optionally lacquered, and said composition being in a agitation independent, orally administratable multi unit, sustained release dosage form.

9. The pharmaceutical composition of claim 8, wherein said dosage form is selected from the group consisting of a capsule, a sachet and a tablet which decomposes into its constituent particles quickly after being administered.

10. The dose form of claim 9 wherein said dosage form is a capsule.