Controlled release device for an active substance

• US 4,803,076 A
• Filed: 09/04/1986
• Issued: 02/07/1989
• Est. Priority Date: 09/04/1986
• Status: Expired due to Term

• Current Assignee: Pfizer Inc.
• Original Assignee: Pfizer Inc.
• Inventors: Ranade, Gautam R.
• Primary Examiner(s): LUSIGNAN, MICHAEL R
• Application Number:
  US06/904,070
• Time in Patent Office: 887 Days
• Field of Search: 424/438, 424/468, 424/475, 424/486, 424/487, 427/3, 604/890, 604/892, 425/352, 425/353
• US Class Current: 424/438
• CPC Class Codes: A61J 3/10 into the form of compressed tablets tablet presses B30B11/00
• CPC Class Codes: A61K 9/0068 Rumen, e.g. rumen bolus
• 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: A61M 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50
• CPC Class Codes: B30B 11/04 co-operating with a fixed mould
• CPC Class Codes: B30B 11/08 co-operating with moulds carried by a turntable
• CPC Class Codes: B30B 15/065 Press rams

Abstract

A device for the controlled release of a substance having useful activity into a fluid medium at a substantially constant rate, said substance contained in a shape which is substantially that of a truncated cone by means of an impermeable wall or coating on the base and side (but not the top) of said truncated cone. Apparatus useful in manufacture when said device is a tablet for administration to a mammal.

Claims

1. A device for the controlled release of one or more active substances into a fluid medium which comprises said substance homogeneously disposed, with or without one or more inert diluents, and contained substantially in the shape of a truncated cone by means of an impermeable wall or coating on the base and side of said truncated cone.

2. A device of claim 1 wherein the truncated cone has a convex base.

3. A device of claim 1 wherein the ratio of the diameters of the top to the base of the truncated cone is in the range of 1:

2 to 1;

4, and the ratio of the height to the diameter of the base is in the range of 1;

1 to 1;

4.

4. A device of claim 3 wherein the truncated cone has a convex base.

5. A device of claim 2 wherein the truncated cone has a concave side.

6. A device of claim 4 wherein the truncated cone has a concave side.

7. A device of claim 1 wherein the substance is biologically active.

8. A device of claim 7 wherein the activity is to prevent or reduce odors in or emanating from the fluid medium.

9. A device of claim 7 wherein the substance has germicidal activity.

10. A device of claim 7 wherein the substance has pharmaceutical activity.

11. A bolus for oral administration into the reticulum or rumen of a ruminant mammal, said bolus being retained in said rumen or reticulum and releasing one or more active agents into the environment of said rumen or reticulum at a substantially constant rate over a prolonged period of time, which comprises said active agent or agents homogeneously disposed in a matrix and contained substantially in the shape of one or a plurality of truncated cones by means of an impermeable wall on the base and side of said truncated cone or cones.

12. A bolus of claim 11 having said active agent contained in a plurality of truncated cone shaped cavities in a plurality of flat cylinders or discs mounted in a carrier of elongated cylindrical shape and spaced to permit of access of the top of said truncated cones to said environment of the rumen or reticulum, said carrier having an attached flexible and resilient flap capable of constrainment in rolled configuration around said elongated cylinder by a constraining means which releases said flap once in the environment of the reticulum or rumen.

13. A bolus of claim 12 wherein the active agent is morantel or a pharmaceutically acceptable salt thereof in a polymer matrix.

14. A tablet for oral administration to a mammal which releases a pharmaceutically active substance into the fluid of the gastrointestinal tract if said mammal at a substantially constant rate over an appreciable time interval which comprises said substance homogeneously disposed, with or without one or more pharmaceutically-acceptable diluents, and contained, substantially in the shape of a truncated cone, by means of an impermeable coating or wall on the base and side of said truncated cone.

15. A tablet of claim 14 wherein the truncated cone has a convex base.

16. A tablet of claim 14 wherein the ratio of the diameters of top to the bottom of the truncated cone is in the range of 1:

2 to 1;

4, and the ratio of the height to the diameter of the base is in the range of 1;

1 to 1;

4.

17. A tablet claim 16 wherein the truncated cone has a convex base.

18. A tablet of claim 15 wherein the truncated cone has a concave side.

19. A tablet of claim 17 wherein the truncated cone has a concave side.

20. A tablet of claim 14 contained by means of coating.

21. A tablet of claim 17 contained by means of coating.

22. A tablet of claim 21 wherein the substance is an antihypertensive.

23. A tablet of claim 22 wherein the substance is prazosin.

24. A tablet of claim 22 wherein the substance is trimazosin.

25. A tablet of claim 22 wherein the substance is doxazosin.

26. A tablet of claim 21 wherein the substance is an antianxiety agent.

27. A tablet of claim 26 wherein the substance is hydroxyzine.

28. A tablet of claim 26 wherein the substance is sertraline.

29. A tablet of claim 21 wherein the substance is a bronchodilator.

30. A tablet of claim 29 wherein the substance is pirbuterol.

31. A tablet of claim 21 wherein the substance is a blood-glucose lowering agent.

32. A tablet of claim 31 wherein the substance is glipizide.

38. A process for the preparation of a tablet of claim 20 which comprises the steps of:

(a) forming uncoated tablets substantially in the shape of a truncated cone in a single-station or multistation tablet press comprising a conventional, substantially round and flat or convex lower punch;

a conventional, corresponding substantially round central die; and

a corresponding upper punch having a cavity which is substantially in the shape of a truncated cone;

(b) fully coating said uncoated tablets with an impermeable coating by conventional means;

(c) removing the coating from the smaller diameter end of the fully coated tablets by means of apparatus comprising a moving horizontal plate having perforations of a shape and size to seat said tablets with the smaller end below the plane of the plate;

a means for seating said fully coated tablets in said perforations;

a stationary support means above said moving plate to hold said tablets in place;

a stationary grinding means below the plane of said plate spaced so as to remove the coating from the smaller diameter end of the fully coated tablets; and

a means for ejecting the finished tablets.

39. A process of claim 38 wherein in step (a) the lower punch is convex.

33. A single-station or multistation tablet press for use in the manufacture of tablets substantially in the shape of a truncated cone which, at each station, comprises

(a) a conventional, substantially round and flat or convex lower punch;

(b) a conventional, substantially round die; and

(c) a corresponding upper punch having a cavity which is substantially in the shape of a truncated cone.

34. A tablet press of claim 33 wherein the lower punch is convex.

35. A tablet press of claim 34 wherein the side of the cone shaped cavity is concave in shape.

36. A tablet press of claim 34 wherein the ratio of the diameters of the top and the base of said truncated cone is in the range of 1:

2 to 1;

4 and the ratio of the height to the diameter of the base is in the range of 1;

1 to 1;

4.

37. An apparatus for removing the coating from the smaller diameter end of a fully coated tablet which is substantially in the shape of a first truncated cone, which comprises

(a) a moving, horizontal plate containing a plurality of perforations substantially in the shape of a second equiangular truncated cone of lesser height, having its larger diameter at the top of the plate and no larger than the larger diameter of said first truncated cone, and its smaller diameter at the bottom of the plate and larger than the smaller diameter of said first truncated cone;

(b) a means for seating said fully coated tablets in said perforations;

(c) a stationary support means above said moving plate to hold the seated tablets in place;

(d) a stationary grinding means below the plane of said plate spaced so as to remove the coating from the smaller diameter end of said supported tablets;

(e) a means of ejecting the finished tablets.