Sustained pulsewise release pharmaceutical preparation

• US 5,011,692 A
• Filed: 12/23/1986
• Issued: 04/30/1991
• Est. Priority Date: 12/28/1985
• Status: Expired due to Fees

• Current Assignee: Sumitomo Pharmaceuticals Company Limited (Sumitomo Chemical Company Limited)
• Original Assignee: Sumitomo Pharmaceuticals Company Limited (Sumitomo Chemical Company Limited)
• Inventors: Sasaki, Yoshio, Tamura, Nobuhiko, Fujioka, Keiji, Takada, Yoshihiro, Sato, Shigeji
• Primary Examiner(s): Lovering, Richard D.
• Assistant Examiner(s): COVERT, JOHN
• Application Number:
  US06/946,158
• Time in Patent Office: 1,589 Days
• Field of Search: 424/484, 424/485, 424/486, 424/425, 424/426, 604/892.1
• US Class Current: 424/426
• 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 9/209 containing drug in at least two layers or in the core and in at least one outer layer

Abstract

The invention relates to sustained pulsewise release pharmaceutical preparation which comprices drug-containing polymeric material layers (layers A) and polymeric material layers containing the drug in question only in a slight amount or free of the drug (layers B) disposed alternatingly, with the whole surface extending in the direction perpendicular to the layer plane being coated with a polymeric material which is insoluble in water or scarcely soluble in water (polymeric material C).

This pharmaceutical preparation of this invention is designed so that active ingredients which should desirably be released pulsewise can be released therefrom in a pulse-like and clinically significant manner and thereby the pharmacological effects of said active ingredients can be maintained for a prolonged period of time.

Claims

1. A sustained pulsewise-release pharmaceutical dosage form means for embedding beneath skin which embedded administration comprises (a) drug-containing polymeric material layers (layers A) and polymeric material layers free from the drug in question or containing only a slight and significantly smaller amount of the same (layers B) disposed alternatingly, and (b) a surface extending in a direction perpendicular to the layers and coated in its entirety with a polymeric material which is insoluble or scarcely soluble in water and in body fluids.

2. A pharmaceutical dosage form of claim 1, wherein the layers B contain no drug at all.

3. A pharmaceutical dosage form of claim 1, wherein layers B contain a drug which is different from the drug contained in layers A.

4. A pharmaceutical dosage form of claim 1, wherein the whole surface extending in a direction perpendicular to the layers and one face extending in a direction parallel to the layers are coated with a polymeric material which is insoluble or scarcely soluble in water and in body fluids.

5. A pharmaceutical dosage form of claim 1, wherein at least layers A or layers B comprise at least one member selected from the group consisting of collagen, gelatin, polylactic acid, polyglycolic acid and poly(lactide-co-glycolide).

6. A pharmaceutical dosage form of claim 1, wherein the polymeric material which is insoluble or scarcely soluble in water and in body fluids is a silicone polymer and covers the surface extending in a direction perpendicular to the layers.

7. A pharmaceutical dosage form of claim 1, wherein the drug is disposed in polymeric material layers, in a form of enclosed particles.

8. A pharmaceutical dosage form of claim 7, wherein the particles are liposome, microcapsules or microspheres.

9. A pharmaceutical dosage form of claim 7, wherein the particles are of a size which is generally within a range of from about 17 nm to about 1000 μ

m.

10. A pharmaceutical dosage form of one of claims 1-8, wherein the drug is a drug which is advantageously administered pulsewise.

11. A sustained pulsewise-release pharmaceutical dosage form of claim 1 which is adapted for embedded use beneath the skin, wherein the drug is one which is administrable by embedding beneath the skin and wherein layers B are substantially free from the drug.

12. A pharmaceutical dosage form of claim 1 wherein the polymeric material of each layer A and that of each layer B is degradable.

13. A pharmaceutical dosage form of claim 6 wherein the silicone polymer also covers a surface extending in a direction parallel to the layers.

16. A dosage form of claim 1, claim 14, or claim 15 in which the drug is a peptide protein type drug for embedded use and which is unstable to heat and to organic solvents.

17. A pharmaceutical dosage form of claim 1, wherein the drug is GRF (1-29).

18. A pharmaceutical dosage form of claim 1, wherein peptide protein type active substance is interferon.

19. An implantable pharmaceutical preparation of one of claims 1-8, wherein the layers A and layers B are layers formed by compression molding.

14. A sustained pulsewise-release pharmaceutical tablet means for embedding beneath the skin and administration comprising a plurality of substantially planar parallel layers surrounded by a surface perpendicular to the layers;

said layers being of at least two different types;

a first type comprising drug-containing polymeric material and being disposed alternatingly with a second type containing polymeric material which is free from or substantially free from the drug in the first type;

the surrounding perpendicular surface being coated with a polymeric material which is insoluble or substantially insoluble in water and in body fluids.

15. A sustained pulsewise-release pharmaceutical dosage form which comprises (a) drug-containing polymeric material layers (layers A) and polymeric material layers free from or substantially free from the drug in question (layers B) disposed alternatingly, and (b) a surface extending in a direction perpendicular to the layers and coated in its entirety with a polymeric material which is insoluble or scarcely soluble in water and in body fluids;

the pharmaceutical preparation being in a form suitable for and the drug being one which is administrable by being embedded beneath the skin.

20. A method of pulsewise administering a pharmaceutical which comprises embedding a dosage form beneath the skin of a host in need of such therapy, and wherein the dosage form is a sustained pulsewise-release pharmaceutical dosage form which comprises (a) drug-containing polymeric material layers (layers A) and polymeric material layers free from the drug in question or containing only a slight and significantly smaller amount of the same (layers B) disposed alternatingly, and (b) a surface extending in a direction perpendicular to the layers and coated in its entirety with a polymeric material which is insoluble or scarcely soluble in water and in body fluids.