METHOD AND PROCESS FOR THE PRODUCTION OF MULTI-COATED RECOGNITIVE AND RELEASING SYSTEMS

• US 20090232858A1
• Filed: 03/03/2009
• Published: 09/17/2009
• Est. Priority Date: 03/12/2007
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Ekerdt, Barbara, Gomez-Burgaz, Marta, Peppas, Nicholas A.
• Granted Patent: US 8,771,713 B2
• Time in Patent Office: Days
• US Class Current: 424/401
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/1676 having a drug-free core with discrete complete coating layer containing drug adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921
• 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 9/5073 having two or more different coatings optionally including drug-containing subcoatings
• CPC Class Codes: A61K 9/5084 Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077

Abstract

The present invention includes compositions, methods, systems for the controlled delivery of an active agent in a tablet polymer comprising two or more layers, wherein each of the two or more layers comprises at least one active agent and at least one molecular recognition polymer, wherein the two or more layers are compressed into a single tablet.

Claims

1. A composition comprising:

a tablet polymer comprising two or more layers, wherein each of the two or more layers comprises at least one active agent and at least one molecular recognition polymer, wherein the two or more layers are compressed into a single tablet.

2. The composition of claim 1, wherein the polymer comprises microparticles.

3. The composition of claim 1, wherein the layers further comprise at least one of an adhesive, a binder, an inactive matrix or an excipient.

4. The composition of claim 1, wherein the polymer is at least one of biocompatible, biodegradable, swellable, water-soluble, or porous.

5. The composition of claim 1, wherein the recognitive portion of the layer is disrupted due to:

osmosis upon the presence and binding of the molecule leading to rupture due to swelling;

change of the solubility of the polymeric network leading to polymer dissolution;

local temperature changes leading to expansion of the polymeric network and combinations thereof.

6. The composition of claim 1, wherein the active agent is loaded into two or more layers.

7. The composition of claim 1, wherein the composition comprises 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 layers.

8. The composition of claim 1, wherein active agent is selected from pharmaceuticals, medical agents, food components, detergents, bleaches, fabric softeners, fragrances, cosmetic products, air fresheners, room deodorant devices, perfumed substrates, perfumed plastics and pet collars.

9. The composition of claim 1, wherein the polymer is selected from Poly(allylamine), Acrylic acid, Acrylamide, (Diethylamino)ethyl methacrylate, (Ethylamino)methacrylate, Methacrylic acid, methylmethacrylate, Triazacyclononane-copper(II) complex, 2-(methacryloyxloxy)ethyl phosphate, methacrylamide, 2-(trifluoromethyl)acrylic acid, 3-aminophenylboronic acid, poly(allylamine), o-phthalic dialdehyde, oleyl phenyl hydrogen phosphate, 4-vinylpyridine, vinylimidazole, 2-acryloilamido-2,2′

-methopropane sulfonic acid, Silica, organic silanes, N-(4-vinyl)-benzyl iminodiacetic acid, Ni(II)-nitrilotriacetic acid, N-acryloyl-alanine, ethylene glycol dimethacrylate, pentaerythritol triacrylate, pentaerythritol tetraacrylate, trimethylolpropane trimethacrylate, vinyl triethoxysilane, vinyl trimethoxysilane, toluene 2,4-diisocyanate, epichlorohydrin, triglycerolate diacrylate, polystyrene surface, Propylene glycol dimethacrylate, poly(ethylene glycol) n dimethacrylate, methacrylate derived silica, acrylonitrile, N,N′

-dimethylacrylamide, poly(ethylene glycol) diacrylate.

10. The composition of claim 1, wherein the tablet further comprises a coating.

11. The composition of claim 1, wherein the tablet is a sphere, film, planar, semi-spherical, cylinder, rod, hemispheres, conical, hemi-cylinders, bi-layer and combination thereof.

12. A composition comprising:

a tablet polymer comprising two or more layers, wherein each of the two or more layers comprises at least one active agent and at least one molecular recognition polymer, wherein the two or more layers are compressed into a single tablet.

13. The composition of claim 12, wherein the polymer comprises microparticles.

14. The composition of claim 12, wherein the layers further comprise at least one of an adhesive, a binder, an inactive matrix or an excipient.

15. The composition of claim 12, wherein the polymer is at least one of biocompatible, biodegradable, swellable, water-soluble, or porous.

16. The composition of claim 12, wherein the recognitive portion of the layer is disrupted due to:

osmosis upon the presence and binding of the molecule leading to rupture due to swelling;

change of the solubility of the polymeric network leading to polymer dissolution;

local temperature changes leading to expansion of the polymeric network and combinations thereof.

17. The composition of claim 12, wherein the active agent is loaded into two or more layers.

18. The composition of claim 12, wherein active agent is selected from pharmaceuticals, medical agents, food components, detergents, bleaches, fabric softeners, fragrances, cosmetic products, air fresheners, room deodorant devices, perfumed substrates, perfumed plastics and pet collars.

19. The composition of claim 12, wherein the polymer is selected from Poly(allylamine), Acrylic acid, Acrylamide, (Diethylamino)ethyl methacrylate, (Ethylamino)methacrylate, Methacrylic acid, methylmethacrylate, Triazacyclononane-copper(II) complex, 2-(methacryloyxloxy)ethyl phosphate, methacrylamide, 2-(trifluoromethyl)acrylic acid, 3-aminophenylboronic acid, poly(allylamine), o-phthalic dialdehyde, oleyl phenyl hydrogen phosphate, 4-vinylpyridine, vinylimidazole, 2-acryloilamido-2,2′

-methopropane sulfonic acid, Silica, organic silanes, N-(4-vinyl)-benzyl iminodiacetic acid, Ni(II)-nitrilotriacetic acid, N-acryloyl-alanine, ethylene glycol dimethacrylate, pentaerythritol triacrylate, pentaerythritol tetraacrylate, trimethylolpropane trimethacrylate, vinyl triethoxysilane, vinyl trimethoxysilane, toluene 2,4-diisocyanate, epichlorohydrin, triglycerolate diacrylate, polystyrene surface, Propylene glycol dimethacrylate, poly(ethylene glycol) n dimethacrylate, methacrylate derived silica, acrylonitrile, N,N′

-dimethylacrylamide, poly(ethylene glycol) diacrylate.

20. The composition of claim 12, wherein the tablet further comprises a coating.

21. The composition of claim 12, wherein the tablet is a sphere, film, planar, semi-spherical, cylinder, rod, hemispheres, conical, hemi-cylinders and combination thereof.

22. The composition of claim 12, wherein the composition comprises 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 layers.

23. A method of making a recognitive release system with limited swelling upon exposure to solvent alone comprising:

selecting one or more molecules for imprinting and one or more active agent;

forming two or more polymeric recognitive network layers about the one or more molecules and the active agent;

removing the molecule from the first and a second polymeric recognitive network; and

compressing the two or more layers into a tablet.

24. The method of claim 23, further comprising the step of coating the tablet.

25. The method of claim 23, wherein the two or more layers are formed about a core.

26. The method of claim 23, wherein the two or more layers are coated into multiple layers.

27. The method of claim 23, wherein the tablet is formed into a sphere, film, planar, semi-spherical, cylinder, rod, hemispheres, conical, hemi-cylinders and combination thereof.

28. The method of claim 23, wherein the polymeric recognitive network is at least partially porous.

29. The method of claim 23, wherein the polymer comprises microparticles.

30. The method of claim 23, wherein the layers further comprise at least one of an adhesive, a binder, an inactive matrix or an excipient.

31. The method of claim 23, wherein the polymer is at least one of biocompatible, biodegradable, swellable, water-soluble, or porous.

32. The method of claim 23, wherein the composition comprises 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 layers.