Method for injection molding manufacture of controlled release devices

• US 6,394,094 B1
• Filed: 05/03/1999
• Issued: 05/28/2002
• Est. Priority Date: 05/01/1998
• Status: Expired due to Term

• Current Assignee: Barr Laboratories Incorporated (Teva Pharmaceutical Industries Limited)
• Original Assignee: Enhance Pharmaceuticals, Inc. (Teva Pharmaceutical Industries Limited)
• Inventors: Cline, John F., McKenna, Michelle, Reid-Haqq, Angela, Gabrielski, Edward J.
• Primary Examiner(s): Brown, Michael A.
• Application Number:
  US09/304,285
• Time in Patent Office: 1,121 Days
• Field of Search: 128/830,831,837 264/255,513 425/130
• US Class Current: 128/830
• CPC Class Codes: A61F 6/08 Pessaries, i.e. devices worn in the vagina to support the uterus, remedy a malposition or prevent conception , e.g. combined with devices protecting against contagion
• CPC Class Codes: B29C 2045/1651 Independent injection runners or nozzles
• CPC Class Codes: B29C 45/1642 having a "sandwich" structure B29C45/1603 takes precedence
• CPC Class Codes: B29C 45/1643 from at least three different materials or with at least four layers
• CPC Class Codes: B29K 2083/005 LSR, i.e. liquid silicone rubbers, or derivatives thereof
• CPC Class Codes: B29K 2101/10 Thermosetting resins
• CPC Class Codes: B29K 2105/0035 Medical or pharmaceutical agents
• CPC Class Codes: B29K 2283/00 Use of polymers having silicon, with or without sulfur, nitrogen, oxygen or carbon only, in the main chain, as reinforcement

Abstract

Thermoset polymer controlled release devices are produced by an injection molding of two or more polymers in a mold to produce a core surrounded by a sheath. The polymers may be injected sequentially or simultaneously.

Claims

1. A co-injection method for producing a controlled release device which comprises a thermoset polymer core containing at least one releasable active agent surrounded by a thermoset polymer sheath, the method comprising of injecting a first thermoset polymer and a second thermoset polymer containing at least one active agent into a mold cavity.

2. The method of claim 1, wherein at least one of the first polymer and the second polymer comprises a silicone polymer.

3. The method of claim 1, wherein the first and second polymer are injected sequentially.

4. The methods of claim 1, wherein the first and second polymer are injected simultaneously.

5. The method of claim 4, wherein the simultaneous injection of the first and second silicone polymers is preceded by injection of the first silicone polymer solely.

14. A toroidal ring produced in accordance with any of claims 1, 6, 7, or 11 for controlled release of at least one active agent comprising a core of thermoset polymer containing the active agent, surrounded by a thermoset polymer sheath.

15. A cylindrical rod produced in accordance with any of claims 1, 6, 7, or 11 for controlled release of at least one active agent comprising a core of thermoset polymer containing the active agent(s), surrounded by a thermoset polymer sheath.

6. A method for producing a device for controlled release of an active agent, comprising:

i) injecting a first thermoset polymer into a mold cavity and effecting at least partial cross-linking of the first polymer;

ii) injecting a second thermoset polymer containing the active agent into the mold.

7. A method for producing a device for controlled release of a plurality of active agents, comprising:

i) injecting a first thermoset polymer into a mold cavity and effecting at least partial cross-linking of the first polymer;

ii) injecting a second thermoset polymer containing a first active agent into the mold;

iii) after injecting the second polymer, injecting a third thermoset polymer containing a second active agent into the mold.

8. The method of claim 7, wherein the first, second and third thermoset polymers may be the same or different.

9. The method of claim 7, wherein at least one of the active agents is a therapeutic drug, peptide or prodrug.

10. The method of claim 9, wherein at least one of the therapeutic drugs is a hormone.

11. A method of producing a device for controlled release of a plurality of active agents, in a mold cavity having a plurality of injection gate openings, comprising:

i) injecting for a first time interval, a first thermoset polymer into the mold cavity through a first gate opening, and a second thermoset polymer through a second gate opening,

ii) injecting, for a second time interval, thermoset polymer containing a first active agent into the mold cavity through the first gate opening, and thermoset polymer containing a second active agent through the second gate opening.

12. The method of claim 11, wherein any of the polymers may be the same as or different from any of the other polymers.

13. The method of claim 11, wherein at least one of the polymers is a silicone polymer.

16. A controlled release device produced by any of the preceding claims 7 or 11 comprising at least a first thermoset polymer containing a first releasable active agent, and a second thermoset polymer containing a second releasable active agent, surrounded by a thermoset polymer sheath.

17. A controlled release device comprising a core of thermoset polymer containing at least one active agent surrounded by a thermoset polymer sheath of non-uniform thickness.

18. The controlled release device of claim 17 wherein said sheath comprises a first thermoset polymer and said polymer containing at least one active agent comprises a second thermoset polymer and wherein said first polymer is the same as or different from said second polymer.

19. The controlled release device of claim 18 wherein at least one of said first thermoset polymer and said second thermoset polymer comprises a silicone polymer.

20. The controlled release device of claim 18 wherein said sheath and said core are formed by co-injecting said first thermoset polymer and said second thermoset polymer into a mold cavity of a mold.

21. The controlled release device of claim 20 wherein said first thermoset polymer and said second thermoset polymer are injected simultaneously.

22. The controlled release device of claim 20 wherein said first thermoset polymer and said second thermoset polymer are injected sequentially.

23. The controlled release device of claim 22 wherein said first thermoset polymer is injected into said mold cavity and partially crosslinked for a first time interval prior to injecting said second thermoset polymer into said mold cavity.

24. The controlled release device of claim 23 wherein said partial crosslinking is effected by heating said mold.

25. A cylindrical rod comprising a core of thermoset polymer containing at least one active agent, surrounded by a thermoset polymer sheath, wherein the thickness of sheath varies along the length of the rod.

26. A cylindrical rod of claim 25, wherein the sheath is relatively thin at one end of the rod, relatively thicker at an opposite end of the rod, and the thickness of the sheath increases substantially uniformly along the length of the rod from the first end to the opposite end.

29. An intravaginal ring of claim 26, wherein the sheath has multiple areas of relative thinness and multiple areas of relative thickness, and the thickness of the sheath increases substantially uniformly from any one thin area to an adjacent thick area.

27. An intravaginal ring comprising a core of thermoset polymer containing at least one active agent, surrounded by a thermoset polymer sheath, wherein the thickness of sheath varies along the circumference of the ring.

28. An intravaginal ring of claim 27, wherein the sheath is relatively thin on a first area of the ring, relatively thicker on a second area diametrically opposite the thin portion and the thickness of the sheath increases substantially uniformly along the circumference of the ring from the first area to the second area.

30. The intravaginal ring of claim 27 wherein said polymer sheath comprises a first thermoset polymer and said polymer containing at least one active agent comprises a second thermoset polymer.

31. The intravaginal ring of claim 30 wherein at least one of said first thermoset polymer and said second thermoset polymer comprises a silicone polymer.

32. The intravaginal ring of claim 31 said core and said sheath are formed by co-injecting said first thermoset polymer and said second thermoset polymer into a cavity of a mold.

33. The intravaginal ring of claim 32 wherein said first thermoset polymer and said second thermoset polymer are injected simultaneously.

34. The intravaginal ring of claim 33 wherein said first thermoset polymer and said second thermoset polymer are injected sequentially.

35. The intravaginal ring of claim 34 wherein said first thermoset polymer is injected into said mold cavity and partially crosslinked for a first time interval prior to injecting said second thermoset polymer into said mold cavity.

36. The intravaginal ring of claim 35 wherein said partial crosslinking is effected by heating said mold.