Controlled release drug dispersion delivery device

• US 5,366,738 A
• Filed: 09/08/1993
• Issued: 11/22/1994
• Est. Priority Date: 07/29/1982
• Status: Expired due to Term

• Current Assignee: Merck Sharp & Dohme Corporation (Merck & Co., Inc.)
• Original Assignee: Merck & Co., Inc.
• Inventors: Pipkin, James D., Rork, Gerald S.
• Primary Examiner(s): Phelan, D. Gabrielle
• Application Number:
  US08/118,836
• Time in Patent Office: 440 Days
• Field of Search: 424/473, 424/480, 424/489, 424/479
• US Class Current: 424/473
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• 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 9/2072 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

Abstract

A device for the controlled delivery of a beneficial agent as a gelatinous dispersion consisting of (i) a core which contains a beneficial agent, a polymer which forms gelatinous microscopic particles upon hydration and if desired an agent to modulate the hydration of the polymer; and (ii) an impermeable, insoluble coating which adheres to and surrounds the core and contains apertures which provide an area for the hydration and release of a dispersion comprising gelatinous microscopic particles.

Claims

1. A drug delivery device for the controlled in situ production and release of a dispersion containing a beneficial agent, consisting essentially of:

(A) a compressed core prepared from an admixture comprising

(i) a therapeutically effective amount of a beneficial agent; and

(ii) a polymer which upon hydration forms gelatinous microscopic particles, the polymer selected from the group consisting of sodium polyacrylate and carboxypolymethylenes prepared from acrylic acid crosslinked with allylethers of sucrose or pentaerythritol and the pharmaceutically acceptable salts thereof;

(B) a water insoluble, water impermeable polymeric coating comprising a polymer and a plasticizer, which surrounds and adheres to the core, the polymer being selected from the group consisting of polyvinyl chloride, cellulose acetate, cellulose acetate butyrate or ethylcellulose, or combinations of these polymers, the plasticizer being selected from the group consisting of diethylphthalate, dibutylsebacate or triethylcitrate, the coating having apertures, exposing between about 1 and about 75% of the core surface, wherein the release rate of drug from the device is a function of the number and size of the apertures.

2. The device of claim 1 wherein the amount of beneficial agent in the core comprises from 0.01% to 75% by weight of the core mixture.

3. The device of claim 1 wherein the beneficial agent is an HMG CoA reductase inhibitor.

4. The device of claim 3 wherein the beneficial agent is chosen from the group consisting of lovastatin, pravastatin and simvastatin.

5. The device of claim 4 wherein the beneficial agent is lovastatin.

6. The device of claim 1 wherein the beneficial agent is an anti-inflammatory.

7. The device of claim 6 wherein the beneficial agent is indomethacin.

8. The device of claim 1 wherein the amount of polymer, which upon hydration produces gelatinous microscopic particles in the core comprises from about 5% to about 75% by weight of the core mixture.

9. The device of claim 1, wherein the core mixture further comprises a polymer hydration modulating agent selected from the group consisting of acids, bases, salts, sugars, surfactants and soluble polymers.

10. The device of claim 9, wherein the polymer hydration modulating agent is selected from the group consisting of sodium citrate, betaine hydrochloride, sodium bicarbonate, sodium carbonate and arginine.

11. The device of claim 1 wherein the apertures in the coating range from 0.1 mm to 20 mm at their widest point.

12. The device of claim 11 wherein the apertures are arranged in an irregular pattern about the surface of the device.

13. The device of claim 12 wherein the number of apertures range from 2 to 1000.

14. The device of claim 13 wherein the number of apertures range from 5 to 100.

15. A drug delivery device of claim 1, for the controlled in situ production and release of a dispersion containing lovastatin, consisting essentially of:

(A) a compressed core prepared from an admixture comprising

(i) a therapeutically effective amount, of lovastatin;

(ii) a polymer which forms gelatinous microscopic particles upon hydration; and

(iii) an effective amount of sodium citrate as a polymer hydration modulating agent;

(B) an insoluble, impermeable polymeric coating comprising cellulose acetate butyrate which surrounds and adheres to the core and containing apertures which expose between 1% and 75% of the core surface.

16. The drug delivery device of claim 15, wherein the polymer is a carboxypolymethylene prepared from acrylic acid cross-linked with allylethers of sucrose or pentaerythritol.

17. The drug delivery device of claim 16, wherein the insoluble, impermeable polymeric coating contains from about three to about 100 apertures.

18. A process for the preparation of the device of claim 1 for the controlled release of an active agent wherein:

(A) the core is prepared by either dry mixing or wet granulating the polymer which upon hydration produces gelatinous microscopic particles, the medicament and other excipients required in the preparation of tablets and compressing the mixture into cores;

(B) coating the entire core with the coating material;

and

(C) drilling apertures through the coating using a laser.