Method and process for the production of multi-coated recognitive and releasing systems

• US 8,771,713 B2
• Filed: 03/03/2009
• Issued: 07/08/2014
• 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: Peppas, Nicholas A., Ekerdt, Barbara, Gomez-Burgaz, Marta
• Primary Examiner(s): Claytor, Renee
• Assistant Examiner(s): Kantamneni, Shobha
• Application Number:
  US12/396,540
• Publication Number:
  US 20090232858A1
• Time in Patent Office: 1,953 Days
• Field of Search: 424/400, 424/464, 424/486, 526/72
• US Class Current: 424/400
• 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 multi-bilayer polymer tablet comprising

a first bilayer comprising at least one first molecular imprinted recognition polymeric first layer comprising an imprint that recognizes a template molecule and at least one first active agent in a second layer, wherein the at least one molecular imprinted recognition polymeric first layer recognizes a first template molecule to release the at least one first active agent;

at least a second bilayer in communication with the first bilayer wherein each second bilayer comprises at least one second molecular imprinted recognition polymeric layer and at least one second active agent in a second layer; and

wherein the at least one second molecular imprinted recognition polymeric layer recognizes a second template molecule to release the at least one second active agent, wherein the first bilayer and the at least a second bilayer are compressed into a single tablet,

wherein the at least one first molecular imprinted recognition polymeric layer and the at least one second molecular imprinted recognition polymeric layer are (poly)methacrylic acid molecular imprinted recognition polymers;

wherein the at least one first active agent and the at least one second active agent are insulin; and

wherein the first template molecule and the second template molecule are glucose.

2. The composition of claim 1, wherein

the at least one second molecular imprinted recognition polymeric layer,

the at least one molecular imprinted recognition polymeric first layer or both further comprises microparticles.

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

4. The composition of claim 1, wherein the at least one second molecular imprinted recognition polymeric layer, the at least one first molecular imprinted recognition polymeric layer or both is at least one of biocompatible, biodegradable, swellable, water-soluble, or porous.

5. The composition of claim 1, wherein the recognitive portion of the bilayer unit 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, further comprising a third layer in communication with the first bilayer, the at least a second bilayer, or both to form a tri-layer and an active agent is loaded into the third layer.

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 the at least one first active agent, the at least one second active agent or both are pharmaceuticals.

9. The composition of claim 1, wherein the multi-bilayer polymer tablet further comprises a coating.

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

11. A composition comprising:

a bilayer polymer tablet comprising at least 2 bilayers wherein each of the at least 2 bilayers comprise;

a first molecular imprinted recognition layer comprising a molecular imprinted recognition polymer comprising poly methacrylic acid comprising an imprint that recognizes a template molecule and

a second active agent layer in contact with the first molecular imprinted recognition layer comprising an active agent wherein the molecular imprinted recognition polymer recognizes a template molecule and exposes the second active agent layer to release the active agent, wherein the first molecular recognition and second active agent layers are compressed into a single tablet wherein the active agent is insulin; and

the template molecule is glucose.

12. The composition of claim 11, wherein the molecular imprinted recognition polymer further comprises microparticles.

13. The composition of claim 11, further comprising at least one of an adhesive, a binder, an inactive matrix or an excipient in the first molecular imprinted recognition layer, the second active agent layer or both.

14. The composition of claim 11, wherein the molecular imprinted recognition polymer is at least one of biocompatible, biodegradable, swellable, water-soluble, or porous.

15. The composition of claim 11, wherein the recognitive portion of the bilayer polymer tablet 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.

16. The composition of claim 11, wherein the active agent is loaded into two or more layers.

17. The composition of claim 11, wherein active agent is selected from pharmaceuticals.

18. The composition of claim 11, wherein the bilayer polymer tablet further comprises a coating.

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

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