Dosage units for controlled release of active material

• US 4,666,702 A
• Filed: 04/11/1985
• Issued: 05/19/1987
• Est. Priority Date: 04/11/1984
• Status: Expired due to Fees

• Current Assignee: Thiemann Arzneimittel Gmbh (UCB SA)
• Original Assignee: Thiemann Arzneimittel Gmbh (UCB SA)
• Inventors: Junginger, Hans E.
• Primary Examiner(s): Rose, Shep K.
• Application Number:
  US06/722,077
• Time in Patent Office: 768 Days
• Field of Search: 424/19-22, 424/32, 424/33, 424/15
• US Class Current: 424/497
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/284 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/2853 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)

Abstract

A drug delivery system in the form of dosage units for controlled release of active material comprising a core and a coating layer enclosing said core.

The coating material contains a microporous synthetic thermoplastic polymer and is compressed into a suitable coating layer enclosing the core with the aid of relatively low compression forces.

Claims

1. A substantially zero order delivery system in the form of dosage units comprising:

(a) a core comprising at least one active material and

(b) a relatively thin, 100 to 600 millimicron thick coating layer enclosing or covering said core comprising compression bonded particles having a particle size between about 25 and about 200 millimicrons of one or more synthetic thermopolastic polymers, at least 50% of which are microporous polymers in the form of particles having open cells therein having an average diameter of 0.1 to 100 millimicrons, with pores having an average diameter smaller than that of the cells, said microporous particles having a total void volume of from about 20% to about 95% by volume, said polymer particulates being formed into the coating layer by conventional compression pressure within the range of from 25 to about 750 Kg. Cm 2.

2. A delivery system according to claim 1 in which the said coating layer is comprised of at least 75% by weight of at least one microporous synthetic thermoplastic polymer and has a thickness varying between 100 and 600 μ

m.

3. A delivery system according to claim 1 characterized in that the coating layer is obtained by applying compressional forces not exceeding about 750 kg/cm².

4. A delivery system according to claim 1, in which the said coating layer contains a wetting agent in a quantity sufficient to accelerate the release of active material but not in amounts great enough to cause the formation of additional pores in the coating layer through the dissolution of materials in said coating layer and in no case exceeding 10% by weight of the total coating material.

5. A delivery system according to claim 4, in which the wetting agent in the coating layer comprises the same active material, as present in the core, said active material being highly soluble in water.

6. A delivery system according to claim 1 characterized in that the synthetic thermoplastic microporous polymer is selected from polyethylene, polypropylene, polylactic acid, polyglycolic acid, copolymer from polylactic acid and polyglycolic acid, and mixtures thereof.

7. A delivery system according to claim 1, in which the active material is a biologically active substance.

8. A drug delivery system according to claim 7 in the form of a tablet.

9. A drug delivery system according to claim 7 in the form of multiple coated particles contained in a capsule.

10. The delivery system of claim 2, wherein the coating layer is obtained by applying a compressional force not exceeding about 750 kg/cm².

11. The delivery system of claim 10, wherein said compressional force is between 100 and 500 kg/cm².

12. The delivery system of claim 2, wherein said coating layer contains a wetting agent in a quantity sufficient to accelerate the release of active material but not in amounts great enough to cause the formation of additional pores in the coating layer through the dissolution of materials in said coating layer and in no case exceeding 10% by weight of the total coating material.

13. The delivery system of claim 3, wherein said coating layer contains a wetting agent in a quantity sufficient to accelerate the release of active material but not in amount great enough to cause the formation of additional pores in the coating layer through the dissolution of materials in said coating layer and in no case exceeding 10% by weight of the total coating material.

14. The delivery system of claim 2 wherein said synthetic thermoplastic microporous polymer is selected from the group consisting of polyethylene, polypropylene, polylactic acid, polyglycolic acid, a copolymer of polylactic acid and polygly colic acid, and mixtures thereof.

15. The delivery system of claim 3 wherein said synthetic thermoplastic microporous polymer is selected from the group consisting of polyethylene, polypropylene, polylactic acid, polyglycolic acid, a copolymer of polylactic acid and polyglycolic acid, and mixtures thereof.

16. The delivery system of claim 4 wherein said synthetic thermoplastic microporous polymer is selected from the group consisting of polyethylene, polypropylene, polylactic acid, polyglycolic acid, a copolymer of polylactic acid and polyglycolic acid, and mixtures thereof.

17. The delivery system of claim 5 wherein said synthetic thermoplastic microporous polymer is selected from the group consisting of polyethylene, polypropylene, polylactic acid, polyglycolic acid, a copolymer of polylactic acid and polyglycolic acid, and mixtures thereof.

18. The delivery system of claim 2, wherein said coating layer is comprised of 90-100% by weight of at least one microporous synthetic thermoplastic polymer and has a thickness varying between 250 and 500 μ

m, and wherein said coating layer is obtained by applying compressional forces of between 100 and 500 kg/cm².

19. The delivery system of claim 1, characterized in that the synthetic thermoplastic polymer particulates comprise one or more homopolymers, compolymers or mixtures thereof selected from among condensation polymers, oxidation polymers and olefinic polymers.

20. The delivery system of claim 19, characterized in that the synthetic thermoplastic polymer particulates comprise one or more homopolymers, copolymers or mixtures thereof selected from among nylon, polylactic acid, polyglycolic acid, polyphenylene oxide, polyethylene, polypropylene, polyvinylchloride, polymethyl-acrylate, polymethylmethacrylate and ethylene-acrylic acid.