Linkers for multipart dosage forms for release of one or more pharmaceutical compositions, and the resulting dosage forms

• US 20090110723A1
• Filed: 10/15/2008
• Published: 04/30/2009
• Est. Priority Date: 10/15/2007
• Status: Abandoned Application

• Current Assignee: Capsugel Belgium NV (Lonza Group AG)
• Original Assignee: Capsugel Belgium NV (Lonza Group AG)
• Inventors: McAllister, Stephen Mark
• Application Number:
  US12/285,844
• Publication Number:
  US 20090110723A1
• Time in Patent Office: Days
• US Class Current: 424/454
• CPC Class Codes: A61J 3/071 into the form of telescopically engaged two-piece capsules
• CPC Class Codes: A61J 3/072 Sealing capsules, e.g. rendering them tamper-proof
• 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 9/4808 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

Abstract

A linker for multicomponent dosage form has a preformed drug substance tablet and an injection molded jacket including one or both axial jacket ends open for dispensing the preformed drug substances. The jacket has snap-fit connection elements on the outer surface adjacent each end for engagement with complementary snap-fit element on capsule-type and cap-type dosage form units. Another multicomponent drug form linker is injection molded with a raised circumferential band and snap-fit elements between the band and respective ends engageable with complementary snap-fit elements on dosage form units to provide compressive abutting contact between ends of the units and the band. The band can have an axially tapered outer surface to accommodate dosage form units of different diameters. Still another multicomponent dosage form linker has separable male and female parts each engageable with, and separately sealing, respective dosage form units to be linked. Circumferential complementary grooves, groove segments, ridges and ridge segment-type snap-fit elements are disclosed, as are dosage forms using the above-described linkers.

Claims

1. A linker for connecting with one or more dosage form units from a group including capsule compartments and closure caps, the linker being configured to include a drug substance and comprising:

a solid drug substance in tablet form, the tablet having a longitudinal axis and being substantially cylindrical with opposed axial end faces;

a jacket radially confining the tablet, the jacket having an outer wall with longitudinal ends, at least one of the jacket longitudinal ends being open for dispensing the drug substance from the respective end face,

wherein the outer wall further includes a snap-fit element located adjacent at least one jacket longitudinal end.

2. The linker as in claim 1, further including the jacket having a closed end wall adjacent to one or the other of said jacket longitudinal ends for substantially blocking tablet drug substance from dispensing from the respective tablet axial end face.

3. The linker as in claim 1, wherein the snap-fit element is selected from circumferential grooves, groove segments, ridges, and ridge segments.

4. The linker as in claim 1, further including a raised circumferential band on the jacket outer wall between the jacket longitudinal ends, the band including a side surface configured for axial abutting contact with the dosage form unit.

5. The linker as in claim 1, wherein at least one of the tablet end faces is exposed and configured to extend axially beyond a respective jacket longitudinal end.

6. The linker as in claim 1, wherein the tablet has a recessed land around the perimeter of at least one tablet axial end faces, and wherein the jacket includes inwardly directed outer wall end edges that engage the recessed land.

7. The linker as in claim 1, wherein the tablet has two or more cylindrical parts in axially abutting contact, wherein the parts are comprised of different drug substances having different compositions and/or different release characteristics.

8. The linker as in claim 4, wherein the linker connects two dosage form units, wherein the raised band has two opposed side surfaces for abuttingly contacting the two units, and wherein the raised band has a top surface configured and dimensioned to transition between outer surfaces of the two dosage form units.

9. The linker as in claim 1, wherein the jacket comprises a material selected from the group consisting of hydroxypropyl cellulose, hydroxypropyl methylcellulose acetate succinate, polyvinyl alcohol, hydroxypropyl methyl cellulose, and acrylic or methacrylic acid-based polymers.

10. A multicomponent dosage form comprising:

a linker unit including

a solid drug substance in tablet form, the tablet having a longitudinal axis and being substantially cylindrical with opposed longitudinal end faces;

a jacket radially confining the tablet, the jacket having an outer wall with longitudinal ends and a raised circumferential band between the jacket longitudinal ends, and

wherein the outer wall further includes a snap-fit element located adjacent at least one longitudinal end, the element being selected from circumferential grooves, groove segments, ridges and ridge segments; and

at least one dosage form unit selected from the group including capsule compartments and closure caps, the dosage form unit having an open end connected to the one jacket longitudinal end, the unit having a snap-fit element complementary to and configured to engage the snap-fit element adjacent the one jacket longitudinal end.

11. The multicomponent dosage form as in claim 10, wherein the linker unit snap-fit element is a circumferential groove and the dosage form unit complementary snap-fit element is a circumferential ridge positioned on an inner wall of the dosage form unit.

12. The multicomponent dosage form as in claim 10, wherein the jacket also has a closed end wall.

13. The multicomponent dosage form of claim 12, wherein the linker jacket and closed wall each comprise a material selected from the group consisting of hydroxypropyl cellulose, hydroxypropyl methylcellulose acetate succinate, polyvinyl alcohol, hydroxypropyl methyl cellulose, and acrylic or methacrylic acid-based polymers.

14. The multicomponent dosage form of claim 10,

wherein the dosage form unit has an inner surface proximate the open end, the dosage form unit complementary snap-fit element being located on a dosage unit inner surface, and

wherein the snap-fit element of the jacket and the complementary snap-fit element of the dosage form unit are configured and longitudinally spaced to provide compressive abutting contact between the jacket raised circumferential band and the open end of the dosage form unit, when the respective snap-fit and complementary snap-fit elements are engaged.

15. The multicomponent dosage form as in claim 10, wherein the raised circumferential band has a side configured for contacting the open end of the dosage form unit, and a longitudinal spacing between the raised band side and the snap-fit element on the longitudinal jacket end is less than a longitudinal spacing between the dosage form unit open end and the complementary snap-fit element on the inner wall of the connected dosage form unit.

16. The multicomponent dosage form of claim 10, wherein the linker unit snap-fit element is a circumferential groove and the dosage form unit complementary snap-fit element is a circumferential ridge.

17. The multicomponent dosage form of claim 16, wherein the circumferential groove has a generally curved or wedge-shaped axial cross-section.

18. A multicomponent dosage product comprising:

a linker unit including

a solid drug substance in tablet form, the tablet having a longitudinal axis and being substantially cylindrical with opposed longitudinal end faces;

a jacket radially confining the tablet, the jacket having an outer wall with opposed longitudinal ends and a raised circumferential band between the jacket ends,

wherein the outer wall further includes a snap-fit element located between the raised circumferential band and one of the longitudinal ends, the snap-fit element being selected from circumferential grooves, groove segments, ridges, and ridge segments; and

a first capsule compartment having an open end connected to the linker unit at the one jacket longitudinal end, the first capsule compartment having a snap-fit element complementary to and engaging the snap-fit element of the one jacket longitudinal end,

wherein the first capsule compartment contains a first drug substance different in composition and/or in release characteristics from the tablet drug substance.

19. The multicomponent dosage form as in claim 18, wherein a closure cap is connected to the linker unit at the other jacket longitudinal end, the closure cap having an open end and a snap-fit element complementary to and engaging another linker unit snap-fit element adjacent the other jacket longitudinal end.

20. The multicomponent dosage form as in claim 18, further including the jacket having a closed end wall adjacent at least one jacket longitudinal end.

21. The multicomponent dosage form of claim 18, wherein the jacket is formed from a material selected from the group consisting of hydroxypropyl cellulose, hydroxypropyl methylcellulose acetate succinate, polyvinyl alcohol, hydroxypropyl methyl cellulose, and acrylic or methacrylic acid-based polymers.

22. The multicomponent dosage form as in claim 19, wherein the linker unit snap-fit elements are circumferential grooves, and the complementary snap-fit elements of the first capsule compartment and closure cap are circumferential ridges positioned on respective inner walls of the first capsule compartment and the closure cap.

23. The multicomponent dosage form of claim 19, wherein the linker unit snap-fit elements and complementary snap-fit elements of the closure cap and first capsule compartment are configured and spaced to provide compressive abutting contact between the raised circumferential band and the open ends of the first capsule compartment and the closure cap.

24. The multicompartment dosage form as in claim 19, wherein the axial lengths between the snap-fit elements and the raised band on the linker unit are respectively less than the axial lengths between the snap-fit elements and open ends of the first capsule compartment and closure cap.

25. The multicompartment dosage form as in claim 19, wherein the raised outer band has a top surface configured and dimensioned to provide a transition between outer surfaces of the first capsule compartment and closure cap.

26. The multicomponent dosage form as in claim 18, wherein the raised band includes one or more apertures configured to allow dispersal of the tablet drug substance radially past through the jacket.

27. The multicomponent dosage form of claim 18, further including a second capsule compartment having an open end connected to the linker unit at the other jacket longitudinal end, the second capsule compartment having a snap-fit element complementary to and engaging a snap-fit element adjacent the other jacket longitudinal end, the second capsule compartment containing a second drug substance different in composition and/or release characteristics from the first drug substance or from the tablet drug substance.

28. The multicomponent dosage form of claim 27, wherein a longitudinal length of the second capsule compartment is greater than a longitudinal length of the first capsule compartment.

29. The multicomponent dosage form of claim 27, wherein a diameter of the second capsule compartment is greater than a diameter of the first capsule compartment.

30. The multicomponent dosage form of claim 27, wherein the linker unit snap-fit elements and complementary snap-fit elements of the first and second capsule compartments are configured and spaced to provide compressive abutting contact between the raised circumferential band and the open ends of the first and second capsule compartments.

31. The multicompartment dosage form as in claim 27, wherein the axial lengths between the snap-fit elements and the raised band on the linker unit are respectively less than the axial lengths between the complementary snap-fit elements and open ends of the first and second capsule compartments.

32. The multicomponent dosage form in claim 27, wherein the snap-fit elements of the first capsule compartment and second capsule compartment are circumferential ridges having a generally rounded axis cross-sectional shape, and wherein the linker snap-fit elements are circumferential grooves having a generally rounded or wedge-shaped cross-section.

33. The multicomponent dosage form as in claim 27, wherein the outer surfaces of the first and second capsule compartments have different diameters and wherein the top surface of the raised circumferential band tapers toward the axis in the direction of the capsule compartment with the smaller diameter.

34. The multicomponent dosage form as in claim 27, wherein the raised circumferential band is configured and dimensioned to provide abutting contact between the ends of the first and second capsule compartments.

35. The multicomponent dosage form as in claim 34, wherein the raised band is wedge shaped.

36. A linker for connecting two dosage form units from the group including capsule compartments and closure caps, the dosage form units each having an open end, the linker comprising:

a substantially cylindrical tube having an interior and a longitudinal axis, the tube also having an outer surface and opposed axial ends;

a raised band disposed on the tube outer surface, the band being located between the opposed axial tube ends and extending circumferentially around the tube outer surface, the raised band having opposed side surfaces configured for compressive abutting contact with the open ends of the dosage form units;

snap-fit elements located on the tube outer surface between the raised band and a respective tube axial end, the snap-fit elements being selected from circumferential grooves, groove segments, ridges, and ridge segments; and

a wall configured to close the tube interior, the wall being positioned along the axis at a location at one of, or between, the tube axial ends.

37. A dosage form comprising:

a linker comprising a substantially cylindrical tube having an interior and a longitudinal axis, the tube also having an outer surface and opposed axial ends;

a raised band positioned on the outer surface, the band being located between the opposed axial tube ends and extending circumferentially around the tube outer surface, the raised band having opposed side surfaces oriented substantially perpendicular to the axis;

snap-fit elements located on the tube outer surface between the raised band and a respective tube axial end, the snap-fit elements being selected from circumferential grooves, groove segments, ridges, and ridge segments;

a wall configured and dimensioned to close the tube, the wall being positioned along the axis one of, or between, the tube axial ends; and

a pair of dosage form units selected from capsule compartments and closure caps connected to the linker axial ends, each of said units having a complementary snap-fit element formed on a respective inner unit surface adjacent an open end and being engaged with a respective snap-fit element on the linker,

wherein the configuration of the snap-fit elements and spacing from the raised band on the linker and the configuration of the complementary snap-fit elements and spacing from the open ends on the dosage form units provides a compressive abutting contact between the open ends of the dosage form units and the respective sides of the raised band.

38. A linker for connecting and separately sealing first and second capsule compartments, the linker comprising:

a first generally cylindrical linker part having an axis and opposed longitudinal ends, the first part also having an outer surface with a diameter, an inner surface with a diameter, and a closed wall, the outer surface including a first snap-fit element configured for engaging a complementary snap-fit element on the first capsule compartment, and the inner surface including another snap-fit element, the first snap-fit element and the another snap-fit element being selected from circumferential grooves, groove segments, ridges, and ridge segments; and

a second generally cylindrical linker part having an axis and opposed longitudinal ends, the second linker part having a large diameter portion adjacent a first end of the second part and a small diameter portion adjacent and extending axially from a second end of the second part, the large and small diameter portions having respective outer surfaces, the second part also having a closed wall,

wherein the outer surface of the large diameter portion includes a second snap-fit element configured for engaging a complementary snap-fit element on the second capsule compartment, the second snap-fit element being selected from circumferential grooves, groove segments, ridges, and ridge segments,

wherein the outer surface of the small diameter portion contains a snap-fit element selected from circumferential grooves, groove segments, ridges, and ridge segments complementary to the another snap-fit element on the inner surface of the first linker part.

39. A linker for connecting and substantially separately sealing a first and a second capsule compartment comprising:

a first linker part including a first axial end and a second axial end and including first and second snap-fit elements disposed adjacent a respective one of the first and second axial ends thereof;

a second linker part include a first axial end and a second axial end and including third and fourth snap-fit elements disposed adjacent a respective one of the first and second axial ends thereof;

wherein the first snap-fit element is configured to selectively engage a complementary snap-fit element on the first capsule compartment, the fourth snap-fit element is configured to selectively engage a complementary snap-fit element on the second capsule compartment, and the second snap-fit element is configured to be complementary to and selectively engageable with the third snap-fit element.

40. An apparatus for containing a drug substance comprising:

a linker element having a generally cylindrical outer wall, a first snap-fit element disposed on an outer surface thereof and at least one closed axial end wall; and

a capsule compartment having a generally cylindrical outer wall, a first complementary snap-fit element disposed on an inner surface thereof, a closed axial end and an open axial end;

wherein the first snap fit element and first complementary snap-fit element are selectively engageable; and

wherein the linker element is configured to substantially seal the drug substance within a region defined by at least the linker outer wall and the closed axial end of the capsule compartment and the closed axial end wall of the linker element when the first snap-fit element and the first complementary snap-fit element are engaged.

41. A dosage form comprising:

a first generally cylindrical capsule compartment having an axis, a closed end, and an open end, the open end including an integral, annular linker member extending axially outward of the open end and having an outer surface with a first snap-fit element located a distance L₁ from the capsule compartment open end;

a second generally cylindrical capsule compartment having an axis, a closed end, and an open end with an inner surface, the second capsule compartment having a second snap-fit element complementary to the first snap-fit element, the second snap-fit element being located on the inner surface and spaced a distance of L₂ from the second capsule open end,

wherein L₂>

L₁ and the first and second snap-fit elements are engageable to connect the first and second capsule compartments with the respective open ends being in compressive abutting contact with each other.