Pharmaceutical products containing thermally-inhibited starches

• US 5,830,884 A
• Filed: 01/31/1996
• Issued: 11/03/1998
• Est. Priority Date: 01/18/1995
• Status: Expired due to Fees

• Current Assignee: Brunob II B.V. (Ingredion Incorporated)
• Original Assignee: National Starch and Chemical Investment Holding Corporation
• Inventors: Thomas, David J., Kasica, James J., Zallie, James P.
• Primary Examiner(s): MacMillan, Keith D.
• Application Number:
  US08/595,008
• Time in Patent Office: 1,007 Days
• Field of Search: 106/206.1, 514/60
• US Class Current: 514/160
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: C08B 30/12 Degraded, destructured or non-chemically modified starch , e.g. mechanically, enzymatically or by irradiation; Bleaching of starch preparation of chemical derivatives of starch C08B31/00

Abstract

Thermally-inhibited starches and flours are used in pharmaceutical products as a diluent, filler, carrier, binder, disintegrant, coating, thickener, moisture sink, and the like. The starches and flours are inhibited by dehydrating the starch or flour to substantially anhydrous or anhydrous and then heat treating the anhydrous or substantially anhydrous starch or flour for a time and at a temperature sufficient to inhibit the starch or flour. The dehydration can be carried out by heating the starch or flour, by extracting the starch or flour with a solvent, or by freeze drying. Preferably, the pH is adjusted to a neutral pH or above prior to the dehydration and heat treatment.

Claims

1. An improved pharmaceutical product containing a pharmaceutically-active ingredient and an effective amount of a thermally-inhibited starch or thermally-inhibited flour which starch or flour is prepared by thermally or non-thermally dehydrating the starch or flour to anhydrous or substantially anhydrous and heat-treating the anhydrous or substantially anhydrous starch or flour for a time for up to 20 hours at 120°

-180°

C., which temperature and time is sufficient to inhibit the starch or flour.

2. The pharmaceutical product of claim 1, wherein the thermally-inhibited starch or flour is a pregelatinized granular or non-granular starch or flour.

3. The pharmaceutical product of claim 1, wherein the thermally-inhibited starch or flour is substantially sterilized and is further characterized by an improved flowability in comparison to a non-thermally inhibited starch or flour.

4. The pharmaceutical product of claim 1, wherein the pH of the starch or flour is raised to neutral or greater prior to the dehydration.

5. The pharmaceutical product of claim 1, wherein the thermally-inhibited starch or flour is a cereal, a tuber, a root or a legume starch or flour.

6. The pharmaceutical product of claim 1, wherein the starch is selected from the group consisting of banana, corn, pea, potato, sweet potato, barley, wheat, rice, sago, amaranth, tapioca, sorghum, V.O. hybrid waxy maize, waxy tapioca, waxy sorghum, waxy rice, waxy barley, waxy potato, a starch containing greater than 40% amylose, and combinations thereof.

7. The pharmaceutical product of claim 6, wherein the starch is corn, waxy maize, potato, wheat, rice, tapioca starch, or high amylose starch.

8. The pharmaceutical product of claim 6, wherein the thermally-inhibited starch is a bleached starch, a derivatized starch, a crosslinked starch, a converted starch, a derivatized and converted starch, a derivatized and crosslinked starch, or a converted and crosslinked starch.

9. The pharmaceutical product of claim 1, wherein the thermally-inhibited starch acts a carrier or a diluent and has improved flow properties.

10. The pharmaceutical product of claim 1, wherein the thermally-inhibited starch acts as a wet granulation binder, a spheronisation binder, or a capsule filling binder.

11. The pharmaceutical product of claim 1, wherein the thermally-inhibited starch acts as a direct compression binder.

12. The pharmaceutical product of claim 1, wherein the active ingredient is moisture sensitive and wherein the thermally-inhibited starch acts as a moisture sink.

13. The pharmaceutical product of claim 1, wherein the thermally-inhibited starch acts as a disintegrant.

14. The pharmaceutical product of claim 1, which is a dusting powder and wherein the thermally-inhibited starch acts as adsorbent.

15. The pharmaceutical product of claim 1, which is a liquid medicament and wherein the thermally-inhibited starch acts as a viscosifier.

16. The pharmaceutical product of claim 15, wherein the liquid medicament is a parenteral injectable composition or an inhalant.

17. The pharmaceutical product of claim 1, which is a suppository and wherein the thermally-inhibited starch acts as a gelling agent.

18. The pharmaceutical product of claim 1, wherein an active ingredient is coated with an aqueous dispersion of the thermally-inhibited starch.

19. The pharmaceutical product of claim 1, wherein the thermally-inhibited starch, after dispersion in water, is characterized by its improved viscosity stability in comparison to the non-thermally-inhibited base starch.

20. The pharmaceutical product of claim 1, wherein the starch is selected from the group consisting of banana, corn, pea, potato, sweet potato, barley, wheat, rice, sago, amaranth, tapioca, sorghum, V.O. hybrid waxy maize, waxy tapioca, waxy sorghum, waxy rice, waxy barley, waxy potato, a starch containing greater than 40% amylose, and combinations thereof.

21. The pharmaceutical product of claim 19, wherein the starch is corn, waxy maize, potato, wheat, rice, tapioca starch, or high amylose starch.

22. The pharmaceutical product of claim 19, wherein the thermally-inhibited starch is a bleached starch, a derivatized starch, a crosslinked starch, a converted starch, a derivatized and converted starch, a derivatized and crosslinked starch, or a converted and crosslinked starch.