IP Library Granted Patent US 12,036,322
Granted Patent B2
US 12,036,322 · App. 17/977,902 · Granted Jul 16, 2024

Gelling multiparticulates

Inventors: Christopher D. Craig (Bend, OR); Cody Prather (Bend, OR)
Assignee: Capsugel Belgium NV
A61K9/1635A61K9/1611A61K9/1652A61K9/1682A61K31/522A61K9/146
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Quick Facts
Patent No.
US 12,036,322
App. No.
17/977,902
Granted
Jul 16, 2024
Kind
B2
Abstract

Multiparticulate compositions including an active agent and a gelling agent are disclosed. The multiparticulate compositions are prepared by an aqueous-based spray and congeal process.

Claims (47)

1. A multiparticulate composition, comprising:

a plurality of gelled particles, comprising

>60 wt % of an active agent,

1 wt % to 6 wt % of a gelling agent comprising gellan gum, carrageenan, agar, pectin, gelatin, or any combination thereof,

0.05 wt % to 1 wt % of an inorganic salt, and

4 wt % to 34 wt % of a water-soluble polymer.

2. The multiparticulate composition of claim 1 , wherein the gelling agent comprises gellan gum, carrageenan, or a combination thereof.

3. The multiparticulate composition of claim 1 , wherein the inorganic salt comprises an alkali metal salt, an alkaline earth metal salt, or a combination thereof.

4. The multiparticulate composition of claim 1 , wherein the inorganic salt is a chloride salt.

5. The multiparticulate composition of claim 1 , wherein:

(i) the gelling agent comprises gellan gum and the inorganic salt comprises calcium chloride; or

(ii) the gelling agent comprises carrageenan and the inorganic salt comprises potassium chloride.

6. The multiparticulate composition of claim 1 , wherein:

(i) a mass ratio of gelling agent to inorganic salt is within a range of 1 to 60;

(ii) a mass ratio of water-soluble polymer to gelling agent is within a range of 1 to 39;

(iii) a mass ratio of water-soluble polymer to inorganic salt is within a range of 4 to 800; or

(iv) any combination of (i), (ii), and (iii).

7. The multiparticulate composition of claim 1 , wherein the plurality of gelled particles comprises from greater than 60 wt % to 95 wt % active agent.

8. The multiparticulate composition of claim 1 , wherein the water-soluble polymer has a weight average molecular weight of 20,000 daltons to 200,000 daltons.

9. The multiparticulate composition of claim 1 , wherein the water-soluble polymer comprises polyvinylpyrrolidone (PVP), a copolymer of vinylpyrrolidone and vinyl acetate (PVP-VA), polyethylene glycol (PEG), polyethylene oxide (PEO), or any combination thereof.

10. The multiparticulate composition of claim 1 , wherein the plurality of gelled particles has an average diameter of from 100 μm to 2 mm as measured by laser diffraction.

11. The multiparticulate composition of claim 1 , further comprising a colorant.

12. The multiparticulate composition of claim 1 , further comprising an outer coating on gelled particles of the plurality of gelled particles.

13. A dosage form, comprising the multiparticulate composition of claim 1 , wherein the dosage form is a capsule, a tablet, or a powder mix.

14. A method of making the multiparticulate composition of claim 1 , the method comprising:

preparing an aqueous suspension comprising an active agent, a gelling agent, an inorganic salt, and a water-soluble polymer, wherein (i) the gelling agent comprises gellan gum, carrageenan, agar, pectin, gelatin, or any combination thereof, (ii) a concentration of the active agent in the aqueous suspension exceeds a solubility limit of the active agent in the aqueous suspension such that the active agent is not completely dissolved in the aqueous suspension, and (iii) a combined mass of the active agent, the gelling agent, and the water-soluble polymer includes >60 wt % of the active agent, 1 wt % to 6 wt % of the gelling agent, 0.05 wt % to 1 wt % of the inorganic salt, and 4 wt % to 34 wt % of the water-soluble polymer;

forming droplets of the aqueous suspension, wherein the droplets are formed at a temperature above a gelation temperature of the aqueous suspension;

cooling the droplets of the aqueous suspension below a gelation temperature of the aqueous suspension, whereby the gelling agent gels to form gelled particles comprising the active agent, the gelling agent, the water-soluble polymer, and water; and

drying the gelled particles.

15. The method of claim 14 , wherein forming droplets of the aqueous suspension comprises dispensing the aqueous suspension onto a spinning disk of a rotary atomizer, whereby the aqueous suspension is atomized into droplets.

16. The method of claim 14 , wherein cooling the droplets of the aqueous suspension comprises convective cooling.

17. The method of claim 14 , wherein preparing the aqueous suspension further comprises:

combining a first portion of the active agent with water preheated to a temperature above the gelation temperature of the aqueous suspension and mixing to form an aqueous solution;

adding the gelling agent and the water-soluble polymer to the aqueous solution and mixing to dissolve the gelling agent and the water-soluble polymer while maintaining the aqueous solution at a temperature above the gelation temperature;

adding the inorganic salt to the aqueous solution and mixing the aqueous solution while maintaining the aqueous solution at a temperature above the gelation temperature;

adding a second portion of the active agent to the aqueous solution to form the aqueous suspension; and

maintaining a temperature of the aqueous suspension above the gelation temperature until forming the droplets of the aqueous suspension.

18. A multiparticulate composition, comprising:

a plurality of gelled particles, comprising

>60 wt % of an active agent,

1 wt % to 6 wt % of a gelling agent comprising gellan gum, carrageenan, agar, pectin, gelatin, or any combination thereof,

0.05 wt % to 1 wt % of an inorganic salt, and

0.1 wt % to 38.9 wt % of a water-soluble polymer,

wherein

(i) a mass ratio of gelling agent to inorganic salt is within a range of 1 to 60,

(ii) a mass ratio of water-soluble polymer to gelling agent is within a range of 1 to 39, and

(iii) a mass ratio of water-soluble polymer to inorganic salt is within a range of 4 to 800.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 19, 2025
From: CAPSUGEL BELGIUM NV
To: LONZA SALES AG
Reel/Frame 071157/0636 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 1, 2022
From: CRAIG, CHRISTOPHER D.; PRATHER, CODY
To: BEND RESEARCH, INC.
Reel/Frame 061614/0530 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 1, 2022
From: BEND RESEARCH, INC.
To: CAPSUGEL BELGIUM NV
Reel/Frame 061614/0550 →
Continuity (3)
Continuation 16755130
Provisional Application 62570406 · Oct 10, 2017
Related Publication 20230063064A1 · Mar 2, 2023