Cellulose capsules and methods for making them

• US 9,050,264 B2
• Filed: 11/08/2010
• Issued: 06/09/2015
• Est. Priority Date: 11/07/2009
• Status: Expired due to Fees

• Current Assignee: University of Iowa Research Foundation
• Original Assignee: University of Iowa Research Foundation
• Inventors: Kumar, Vijay, Bhatt, Bhavik
• Primary Examiner(s): Lundgren, Jeffrey S.
• Assistant Examiner(s): SCHMITT, MICHAEL J
• Application Number:
  US13/508,409
• Publication Number:
  US 20120277323A1
• Time in Patent Office: 1,674 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/1611 Inorganic compounds
• CPC Class Codes: A61K 9/1623 Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
• CPC Class Codes: A61K 9/1641 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
• CPC Class Codes: A61K 9/4816 Wall or shell material
• CPC Class Codes: A61K 9/485 Inorganic compounds
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds

Abstract

Disclosed are cellulose capsules, methods for preparing a cellulose capsule, and compositions comprising cellulose capsules, including sustained- or controlled-release dosage forms comprising cellulose capsules.

Claims

1. A pharmaceutical dosage form comprising

(a) a capsule shell comprising regenerated cellulose;

(b) one or more pharmaceutically active agents disposed within the capsule shell; and

(c) optionally, a pharmaceutically acceptable formulation agent disposed within the capsule shell,

wherein the amount of regenerated cellulose in the capsule shell is about 50% (w/w) or more of the capsule shell, and wherein the regenerated cellulose is present in the capsule shell in an amount that is effective to render the capsule non-disintegrating and non-dissolving in aqueous medium at a physiological temperature and pH.

2. The pharmaceutical dosage form of claim 1, wherein the capsule shell further comprises a cellulose derivative.

3. The pharmaceutical dosage form of claim 1, wherein the capsule shell further comprises at least one compound selected from coating agents, polymers, copolymers, colorants, or plasticizers, or any combination thereof.

4. The pharmaceutical dosage form of claim 1, wherein the capsule shell has at least one layer consisting essentially of regenerated cellulose.

5. The pharmaceutical dosage form according to claim 1, wherein the capsule shell consists essentially of regenerated cellulose.

6. The pharmaceutical dosage form of claim 1, wherein the capsule shell further comprises one or more capsule shell permeability modifiers.

7. The pharmaceutical dosage form of claim 1, wherein the capsule shell further comprises one or more capsule shell porosity modifiers.

8. The pharmaceutical dosage form of claim 1, wherein the release profile of the dosage form in aqueous medium exhibits a zero-order release rate at a physiological pH and temperature.

9. The pharmaceutical dosage form according to claim 1, wherein the capsule shell is prepared by a method comprising

(a) providing a methylolcellulose solution;

and

(b) forming the capsule shell from the methylolcellulose solution.

10. The pharmaceutical dosage form of claim 9, wherein providing the methylolcellulose solution comprises

(a1) providing a source of cellulose;

and

(a2) treating the cellulose with paraformaldehyde in anhydrous polar aprotic solvent under conditions suitable to form the methylolcellulose solution.

11. The pharmaceutical dosage form of claim 9, wherein the forming step (b) comprises contacting the methylolcellulose solution with a pin structure and removing the pin structure from the methylolcellulose solution for a time and under conditions that are effective to form a methylolcellulose coating on the pin structure, and wherein the pin structure comprises dimensions that correspond to a capsule size of about size 5 to about size 000.

12. The pharmaceutical dosage form of claim 9, wherein the forming step (b) comprises forming a layer of methylolcellulose, then converting the methylolcellulose to regenerated cellulose by exposing it to water.

13. The pharmaceutical dosage form of claim 1, wherein the release profile of the dosage form in aqueous medium exhibits an apparent zero-order release rate at a physiological pH and temperature.

14. The pharmaceutical dosage form of claim 1, wherein the release profile of the dosage form in aqueous medium exhibits a first order release rate at a physiological pH and temperature.

15. The pharmaceutical dosage form of claim 1, wherein the amount of regenerated cellulose in the capsule shell is more than about 80% (w/w) of the capsule shell.

16. The pharmaceutical dosage form of claim 15, wherein the capsule shell has a thickness in the range of 0.07 mm to 0.1 mm.

17. The pharmaceutical dosage form of claim 15, wherein the capsule shell has a thickness in the range of 0.053 mm to 0.1 mm.

18. The pharmaceutical dosage form of claim 1, wherein the amount of regenerated cellulose in the capsule shell is more than about 90% (w/w) of the capsule shell.

19. The pharmaceutical dosage form of claim 1, wherein the capsule shell has a thickness in the range of 0.07 mm to 0.1 mm.

20. The pharmaceutical dosage form of claim 1, wherein the capsule shell has a thickness in the range of 0.053 mm to 0.1 mm.

21. The pharmaceutical dosage form of claim 1, wherein the capsule shell has a capsule size in the range of about size 5 to about size 000.

22. The pharmaceutical dosage form of claim 21, wherein the capsule shell has a thickness in the range of 0.053 mm to 0.1 mm.

23. The pharmaceutical dosage form of claim 1, wherein the pharmaceutically acceptable formulation agent is disposed within the capsule shell.