Printing or dispensing a suspension such as three-dimensional printing of dosage forms

• US 20040091516A1
• Filed: 11/03/2003
• Published: 05/13/2004
• Est. Priority Date: 10/29/2001
• Status: Abandoned Application

• Current Assignee: Therics Inc.
• Original Assignee: Massachusetts Institute of Technology, Therics Inc.
• Inventors: Bornancini, Esteban R.N., Cima, Michael J., Sherwood, Jill K., Wang, Chen-Chao, Gaylo, Christopher M., Fairweather, James A., Pryce Lewis, Wendy E., Rowe, Charles William
• Application Number:
  US10/700,783
• Publication Number:
  US 20040091516A1
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61J 3/10 into the form of compressed tablets tablet presses B30B11/00
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• 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 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• 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 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61K 9/2893 Tablet coating processes mechanical aspects A61J3/06
• CPC Class Codes: B33Y 10/00 Processes of additive manufacturing
• CPC Class Codes: B33Y 70/00 Materials specially adapted for additive manufacturing
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing

Abstract

The invention includes dispensing a suspension containing solid particles for use in manufacturing a dosage form or other biomedical article by 3DP. The suspension contains solid particles suspended in a liquid. The solid particles may be one or more Active Pharmaceutical Ingredients. The solid particles may be particles of material that are insoluble in the liquid, or they may be particles of a substance that have already dissolved in the liquid up to the saturation level and are present in a concentration beyond what can be dissolved. In addition to solid particles, the liquid may also contain other substances dissolved in it, either substances containing Active Pharmaceutical Ingredients (API) or substances without API. One aspect of the invention includes prevention of agglomeration by adding one or more of several categories of additives to the suspending liquid. Another aspect of the invention includes manipulating the surface charge of the particles in an API suspension to prevent particles from agglomerating. A further aspect of the invention includes an amorphous API that has a greater bioavailability than the corresponding crystalline material. Yet another aspect of the present invention includes a system for providing continuous circulation of the suspension such that the solid particles remain dispersed in the suspension.

Claims

1. A method of manufacturing a biomedical article, comprising:

depositing a layer of powder;

dispensing, onto portions of the layer of powder, a suspension comprising solid particles of at least one substance selected from the group consisting of;

cells, cell fragments, cellular material, proteins, growth factors, bone particles, cartilage particles, other biological or inert materials which are insoluble or nearly insoluble, Active Pharmaceutical Ingredients, and very fine particles of the same material as the powder in the layer of powder;

and repeating the above steps as many times as needed to produce the biomedical article.

2. The method of claim 1 wherein the suspension further comprises suspending agents and/or steric hindrants.

3. The method of claim 1 wherein the suspension further comprises one or more additional API dissolved in the liquid.

4. The method of claim 1 wherein the suspension further comprises one or more binding substances dissolved in the liquid.

5. The method of claim 1 wherein the biomedical article is an implantable device.

6. The method of claim 1 wherein the biomedical article is a bone substitute.

7. The method of claim 1, further comprising, after dispensing, allowing or causing the dispensed suspension to at least partially dry, and dispensing a second suspension containing solid particles of at least one Active Pharmaceutical Ingredient again onto portions of the layer of excipient powder, at least one additional time before depositing the next layer of excipient powder.

8. The method of claim 7 wherein the pattern of deposition during the second printing is different from the pattern during the first printing.

9. The method of claim 1, wherein at least some of the suspended solid particles comprise an amorphous form of Active Pharmaceutical Ingredient.

10. The biomedical article of claim 7 wherein the second substance has a local concentration at local places in the dosage form and wherein the local concentration of the second substance is nonuniform.

11. The biomedical article manufactured by the method of claim 1.

12. A biomedical article comprising:

a powder which is substantially insoluble;

a second substance selected from the group consisting of;

cells, cell fragments, cellular material, proteins, growth factors, bone particles, cartilage particles, other biological or inert materials which are insoluble or nearly insoluble, Active Pharmaceutical Ingredients, and very fine particles of the same material as the powder in the layer of powder.

14. The method of claim 12 wherein the valve includes a valve body and within the valve body a seat and a moving part, and a bypass flowpath.

15. The method of claim 12 further comprising flowing suspension continuously through a manifold, and wherein the microvalve is supplied from the manifold.

13. A method of three-dimensional printing, comprising dispensing a suspension through a solenoid-operated valve onto powder.

16. The method of claim 13, wherein the solenoid-operated valve has a valve body and within the valve body a seat and a moving part adapted to fit against the seat and thereby close a flowpath, and further comprising a bypass path emanating from the valve body close to the valve seat, the bypass path being always open.