Gelling multiparticulates

Patent metadata

Field	Value
Publication number	US-11510877-B2
Application number	US-201816755130-A
Country	US
Kind code	B2
Filing date	Oct 9, 2018
Priority date	Oct 10, 2017
Publication date	Nov 29, 2022
Grant date	Nov 29, 2022

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.

First claim

We claim:

1. A multiparticulate composition comprising a plurality of particles comprising:
>60 wt % of an active agent;
1-6 wt % of a gelling agent;
0.05-1 wt % of an inorganic salt; and
up to 38.95 wt % of a water-soluble polymer, 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.

2. The multiparticulate composition of claim 1 , wherein the gelling agent comprises gellan gum, carrageenan, agar, pectin, or any 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 3 , 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.

5. The multiparticulate composition of claim 1 , wherein the water-soluble polymer comprises PVP having a weight average molecular weight of from 30,000 to 50,000 daltons.

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

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

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

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

10. The multiparticulate composition of claim 1 , consisting essentially of:
the active agent;
the gelling agent;
the inorganic salt;
the water-soluble polymer;
0-2 wt % of a colorant; and
optionally, an outer coating on the particles.

11. A multiparticulate composition comprising a plurality of particles comprising:
>60 wt % of caffeine:
1-6 wt % of a gelling agent; and
up to 39 wt % of a water-soluble polymer, 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.

12. A multiparticulate composition comprising a plurality of particles comprising:
75-95 wt % caffeine;
1-3 wt % gellan gum, carrageenan, or a combination thereof;
0.05-0.3 wt % calcium chloride, potassium chloride, or a combination thereof; and
1-23.95 wt % PVP.

13. 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 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, (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, 1-6 wt % of the gelling agent, 0.05-1 wt % of the inorganic salt, and up to 38.95 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;
forming congealed particles from the droplets, the congealed particles comprising the active agent, the gelling agent, the water-soluble polymer, and water; and
drying the congealed particles to form a plurality of dried particles comprising >60 wt % of the active agent, 1-6 wt % of the gelling agent, and up to 39 wt % of the water-soluble polymer.

14. The method of claim 13 , 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.

15. The method of claim 13 , wherein forming the congealed particles from the droplets comprises cooling the droplets of the aqueous suspension to a temperature below the gelation temperature of the aqueous suspension.

16. The method of claim 15 , wherein cooling the droplets of the aqueous suspension comprises convective cooling.

17. The method of claim 13 , 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. The method of claim 13 , further comprising applying a coating to the plurality of dried particles.

Assignees

• Capsugel Belgium Nv

Inventors

• Craig Christopher D
• Prather Cody

Classifications

• A61K9/146

  with organic macromolecular compounds · CPC title

• A23P10/30

  Encapsulation of particles, e.g. foodstuff additives · CPC title

• A61K31/4166

  having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin · CPC title

• A61K9/1682

  Processes · CPC title

• A61K9/1611 Primary

  Inorganic compounds · CPC title