HOT-MELT EXTRUDED PHARMACEUTICAL DOSAGE FORM

• US 20110038930A1
• Filed: 07/21/2010
• Published: 02/17/2011
• Est. Priority Date: 07/22/2009
• Status: Active Grant

• Current Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Original Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Inventors: BARNSCHEID, Lutz, Galia, Eric
• Granted Patent: US 10,080,721 B2
• Time in Patent Office: Days
• US Class Current: 424/468
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• 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: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• 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 9/2095 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: A61P 25/04 Centrally acting analgesics, e.g. opioids

Abstract

The invention relates to a hot-melt extruded pharmaceutical dosage form with controlled release of a pharmacologically active ingredient (A) embedded in a matrix comprising a polymer (C), the dosage form exhibiting a breaking strength of at least 300 N and having an oblong shape comprising a longitudinal direction of extension, a transversal direction of extension orthogonal to the longitudinal direction of extension, a front side, an opposite back side and a circumferential rim between said front and back side;

wherein

• • the core of the pharmaceutical dosage form has a morphological orientation caused by hot-melt extrusion that is substantially orthogonal to the longitudinal direction of extension of the dosage form; and/or
  • the release per area of the pharmacologically active ingredient (A) through the front side and the opposite back side is faster than the release through the circumferential rim.

Claims

1. A hot-melt extruded pharmaceutical dosage form with controlled release of a pharmacologically active ingredient (A) embedded in a matrix comprising a polymer (C), the dosage form having an oblong shape comprising a longitudinal direction of extension, a transversal direction of extension orthogonal to the longitudinal direction of extension, a front side, an opposite back side and a circumferential rim between said front and back side;

wherein

the core of the pharmaceutical dosage form has a morphological orientation caused by hot-melt extrusion that is substantially orthogonal to the longitudinal direction of extension of the dosage form; and

/or

the release per area of the pharmacologically active ingredient (A) through the front side and the opposite back side is faster than the release through the circumferential rim.

2. The dosage form according to claim 1, wherein the morphological orientation caused by hot-melt extrusion is substantially orthogonal to the transversal direction of extension of the dosage form.

3. The dosage form according to claim 1 or 2, which comprises a monolithic core.

4. The dosage form according to any of the preceding claims, wherein the pharmacologically active ingredient (A) is an opioid.

5. The dosage form according to any of the preceding claims, wherein polymer (C) is a polyalkylene oxide having a weight average molecular weight of at least 200,000 g/mol.

6. The dosage form according to any of the preceding claims, wherein the content of polymer (C) is at least 30 wt.-%, based on the total weight of the dosage form.

7. The dosage form according to any of the preceding claims, wherein the relative length ratio of the longitudinal direction of extension to the transversal direction of extension is at least 1.1:

1.

8. The dosage form according to any of the preceding claims, which comprises a film coating.

9. The dosage form according to any of the preceding claims, which releases the pharmacologically active ingredient (A) under in vitro conditions in artificial gastric juice according to the following release profile:

after 0.5 h at least 5 wt.-%,

after 1 h at least 10 wt.-%,

after 3 h at least 20 wt.-%,

after 6 h at least 35 wt.-%, and

after 12 h at least 55 wt.-%,

based on the total weight of the pharmacologically active ingredient (A) initially contained in the dosage form.

11. The process according to claim 10, which is for the manufacture of a dosage form according to any of claims 1 to 9.

10. A process for the manufacture of a hot-melt extruded pharmaceutical dosage form with controlled release of a pharmacologically active ingredient (A) embedded in a matrix comprising a polymer (C), the dosage form exhibiting a breaking strength of at least 300 N and having an oblong shape comprising a longitudinal direction of extension, a transversal direction of extension orthogonal to the longitudinal direction of extension, a front side, an opposite back side and a circumferential rim between said front and back side, comprising the steps of

(a) hot-melt extruding a mass comprising

the pharmacologically active ingredient (A) and

the polymer (C),

through an oblong die thereby obtaining an extrudate with an oblong cross-section;

(b) cutting said extrudate into slices having two opposing cut surfaces of oblong shape;

(c) placing said slices into a tabletting tool comprising upper punch and lower punch in a manner so that the opposing surfaces of oblong shape face said upper and lower punch, respectively;

(d) press-forming dosage forms from the slices; and

(e) optionally, applying a film coating.

12. The process according to claim 10 or 11, wherein step (a) is performed by means of w twin-screw-extruder.

13. The process according to any of claims 10 to 12, wherein at least 50% of the total surface of the slices obtained in step (b) is formed by the two opposing cut surfaces.

14. A hot-melt extruded pharmaceutical dosage form obtainable by the process according to any of claims 10 to 13.