Multi-component pharmaceutical dosage form

• US 7,691,407 B2
• Filed: 12/15/2006
• Issued: 04/06/2010
• Est. Priority Date: 07/30/1999
• Status: Expired due to Fees

• Current Assignee: Capsugel Belgium NV (Lonza Group AG)
• Original Assignee: Smithkline Beecham PLC (GlaxoSmithKline PLC)
• Inventors: Clarke, Allan J, Kift, Ron, Lightfoot, Donald, Harris, Geoffrey Arthur, Ofsharick, Thomas, Fonio, Teodoro, Szymczack, Margaret Mary, McGinley, Shane
• Primary Examiner(s): TRAN, SUSAN T
• Application Number:
  US11/611,281
• Publication Number:
  US 20070087049A1
• Time in Patent Office: 1,208 Days
• Field of Search: None
• US Class Current: 424/453
• CPC Class Codes: A61J 3/07 into the form of capsules or similar small containers for oral use
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A multi-component pharmaceutical dosage form comprising a plurality of drug substance—containing sub-units, being capsule compartments and/or solid sub-units comprising a solid matrix of a polymer which contains a drug substance, the sub-units being connected together in the assembled dosage form by a weld between parts of the assembled dosage form.

Claims

1. A multi-component pharmaceutical dosage form which comprises:

a plurality of sub-units, each sub-unit being selected from the group consisting of;

a linker, a closure cap, a drug substance-containing capsule compartment which is soluble or disintegrable in a patient'"'"'s gastrointestinal environment for release of the drug substance contained in the capsule compartment, and a solid matrix comprising a polymer and containing a drug substance, the polymer being soluble, dispersible or disintegrable in a patient'"'"'s gastrointestinal environment for release of the drug substance contained in the solid matrix, in which the plurality of sub-units are disposed in end-to-end relationship along a line that defines an axial direction, each of the plurality of sub-units including an outer wall surrounding said line, and

a plurality of joints, in which each of said plurality of sub-units is joined to at least one other sub-unit by one of the plurality of joints, each joint comprising a plug formed as a unitary part of one respectively joined sub-unit and a socket formed as a unitary part of the other respectively joined sub-unit,

wherein the plurality of sub-units includes at least two drug substance containing sub-units each respectively including a socket and at least one linker sub-unit including a pair of plugs on opposed axial ends thereof, each of said pair of plugs being engaged with a respective one of said two drug substance-containing sub-units, and

wherein the plurality of joints includes at least two first joints respectively formed between the two drug substance-containing sub-units and the one linker such that the relative axial position between each of the respective two drug substance-containing sub-units and the one linker sub-unit is solely delimited by engaging outer wall axial end parts of the respective two drug substance-containing sub-units and engaging outer wall axial end parts of the one linker sub-unit.

2. The dosage form as in claim 1 wherein the engaging outer wall axial end parts of the two drug substance-containing sub-units and the engaging axial end parts of the one linker sub-unit are complementary tenon parts.

3. The dosage form as in claim 1 wherein the engaging outer wall axial end parts of the two drug substance-containing sub-units and the engaging axial end parts of the one linker sub-unit are complementary axially abutting beveled parts.

4. The dosage form as in claim 1 wherein one or more of the plurality of joints are welded joints.

5. The dosage form as in claim 1 wherein the drug substances in said two drug substance-containing sub-units differ in composition and/or in release characteristics.

6. The dosage form as in claim 1 wherein each of said plugs of said plurality of sub-units is interchangeable and each of said sockets of said plurality of sub-units is interchangeable.

7. The dosage form as in claim 1 wherein each of the sockets of the two drug substance-containing sub-units is configured to be engaged with either of the two plugs of the one linker sub-unit.

8. The dosage form as in claim 1 wherein each of the plugs in the one linker sub-unit is configured to be engaged with either of the sockets of the two drug substance-containing sub-units.

9. The dosage form as in claim 1, wherein at least one of said two drug substance-containing sub-units is a capsule compartment sub-unit having a socket open to the drug substance contained therein when not joined, and wherein the plug of the one linker sub-unit joined to the socket of said one drug substance-containing capsule-containing sub-unit provides closure for the contained drug substance.

10. The dosage form as in claim 1, wherein one or more of the first plug and socket joints is secured by a mechanical interlock.

11. The dosage form as in claim 10, wherein the mechanical interlock is at least one of a friction fit, a snap-fit, and a screw fit.

12. The dosage form as in claim 11 wherein the mechanical interlock includes a snap-fit provided by complementary co-operating bead and groove elements or ridge and groove elements, the complementary elements being located on the respective plug and socket parts.

13. The dosage form as in claim 1, wherein the two drug substance-containing sub-units are capsule compartment sub-units, wherein the outer walls of the two capsule compartment sub-units are formed of polymers that are soluble, dispersible, or disintegrable in a gastro-intestinal environment, and wherein the outer polymer walls at least in part determine the release characteristics of the respective contained drug substances.

14. The dosage form as in claim 13, wherein the outer. polymer walls of the two drug substance-containing capsule compartments are constructed to provide a predetermined dosing profile for the contained drug substances.

15. A multi-component pharmaceutical dosage form which comprises a plurality of sub-units, each sub-unit being selected from the group consisting of:

a linker, a closure cap, a drug substance-containing capsule compartment which is soluble or disintegrable in a patient'"'"'s gastro-intestinal environment for release of the drug substance contained in the capsule compartment, and a solid matrix comprising a polymer and containing a drug substance, the polymer being soluble, dispersible or disintegrable in a patient'"'"'s gastro-intestinal environment for release of the drug substance contained in the solid matrix, in which dosage form the plurality of sub-units are disposed in end-to-end relationship along a line, and each includes an outer wall surrounding said line, and

a plurality of joints, in which each of said plurality of sub-units is joined to at least one other sub-unit by one of the plurality of joints, each joint comprising a plug forming a unitary part of one of the respectively joined sub-units and a socket formed as a unitary part of the other of the respectively joined sub-units,

wherein the plurality of joints includes at least two first joints formed between respective first and second sub-units wherein the relative position between the respective first and second sub-units is solely delimited by engaging outer wall axial end parts of the respective first and second sub-units,

wherein the plurality of sub-units includes at least two drug substance-containing capsule compartment sub-units,

wherein at least the outer walls of said two drug substance-containing capsule compartment sub-units are formed of polymers, the polymers being soluble, dispersible or disintegrable in a patient'"'"'s gastro-intestinal environment, and

wherein the release characteristics of the outer polymer walls of said two capsule compartment sub-units are different.

16. The dosage form as in claim 15 wherein the outer polymer walls are formed of different polymers to achieve different release characteristics for the two capsule compartment sub-units.

17. The dosage forms as in claim 15 wherein the polymers are chosen to release the respective drug substances at different locations in the gastro-intestinal environment for each of said two capsule compartment sub-units.

18. The dosage form as in claim 15 wherein the thicknesses of the outer polymer walls are different to achieve different release characteristics for the two capsule compartment sub-units.

19. The dosage forms as in claim 15 wherein the outer polymer wall of one of said two drug substance-containing sub-units has an area or point of weakness which preferentially dissolves, disperses or disintegrates relative to the outer polymer wall of the other of said two drug substance-containing sub-units to achieve different release characteristics for the two-capsule compartment sub-units.