Formulation of sparingly soluble compounds by hot-melt extrusion

Patent metadata

Field	Value
Publication number	US-10022337-B2
Application number	US-201415034242-A
Country	US
Kind code	B2
Filing date	Nov 14, 2014
Priority date	Nov 15, 2013
Publication date	Jul 17, 2018
Grant date	Jul 17, 2018

Abstract

The present invention relates to formulation of sparingly-(water)-soluble compounds and its use as (or in a) food or feed product or dietary supplement.

First claim

The invention claimed is:

1. A hot-melt extruded formulation comprising:
(i) 0.5-50 wt-%, based on the total weight of the hot melt extruded formulation, of at least one compound having low permeability and low solubility selected from the group consisting of α-carotene, β-carotene, 8′-apo-β-carotenal, 8′-apo-β-carotenoic acid esters, canthaxanthin, astaxanthin, lycopene, lutein, zeaxanthin and crocetin,
(ii) 50-99.5 wt-%, based on the total weight of the hot melt extruded formulation, of at least one polymeric carrier material selected from the group consisting of ethyl cellulose (EC), hydroxypropylmethyl cellulose (HPMC), alginate, chitosan, corn starch, potato starch, polyvinylpyrrolidon (PVP), polyvinylacetate (PVA), polylactic acid (PLA), poly(methacrylic acid-co-ethyl acrylate) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, and
(iii) up to about 40 wt-%, based on the total weight of the hot melt extruded formulation, of at least one plasticizer selected from the group consisting of ethylene glycol, 1,2-butylene glycol, 2,3-butylene glycol, styrene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, monopropylene glycol monoisopropyl ether, propylene glycol monoethyl ether, ethylene glycol monoethyl ether, diethylene glycol monoethyl ether, sorbitol lactate, ethyl lactate, butyl lactate, ethyl glycolate, dibutylsebacate, acetyltributylcitrate, triethyl citrate, acetyl triethyl citrate, tributyl citrate and allyl glycolate.

2. The hot-melt extruded formulation according to claim 1 , wherein the compound having low permeability and low solubility is in an amorphous form.

3. The hot-melt extruded formulation according to claim 1 , wherein the at least one plasticizer is present in an amount of 10-40 wt-%, based on the total weight of the hot-melt extruded formulation.

4. The hot-melt extruded formulation according to claim 1 , further comprising at least one antioxidant.

5. The hot-melt extruded formulation according to claim 4 , wherein the at least one antioxidant is selected from the group consisting of ascorbic acid, ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, hypophophorous acid, monothioglycerol, sodium ascorbate, sodium formaldehyde sulfoxylate, sodium metabisulfite, vitamin C, BHT, BHA, sodium bisulfite, vitamin E and derivatives thereof, and propyl gallate.

6. The hot-melt extruded formulation according to claim 4 , wherein the at least one antioxidant is present in an amount up to 5 wt-%, based on the total weight of the hot-melt extruded formulation.

7. The hot-melt extruded formulation according to claim 1 , wherein the formulation comprises:
(i) 5-20 wt-%, based on the total weight of the hot melt extruded formulation, of the at least one compound having low permeability and low solubility,
(ii) 80-95 wt-%, based on the total weight of the hot melt extruded formulation, of the at least one polymeric carrier material, and
(iii) 10-40 wt-%, based on the total weight of the hot melt extruded formulation, of the at least one plasticizer.

8. The hot-melt extruded formulation according to claim 1 , wherein the formulation comprises:
(i) 5-10 wt-%, based on the total weight of the hot melt extruded formulation, of the at least one compound having low permeability and low solubility,
(ii) 90-95 wt-%, based on the total weight of the hot melt extruded formulation, of the at least one polymeric carrier material, and
(iii) 10-40 wt-%, based on the total weight of the hot melt extruded formulation, of the at least one plasticizer.

9. A food product, feed product and/or dietary supplement comprising the hot-melt extruded formulation according to claim 1 .

10. A premix for a food product, feed product and/or dietary supplement comprising the hot-melt extruded formulation according to claim 1 .

11. A hot-melt extrusion process for the production of a hot melt extruded formulation, wherein the process comprising conducting hot-melt extrusion in the absence of a solvent of formulation components comprising:
(i) 0.5-50 weight-% (wt-%), based on the total weight of the hot-melt extruded formulation, of at least one compound having low solubility selected from the group consisting of α-carotene, β-carotene, 8′-apo-β-carotenal, 8′-apo-β-carotenoic acid esters, canthaxanthin, astaxanthin, lycopene, lutein, zeaxanthin and crocetin,
(ii) 50-99.5 wt-%, based on the total weight of the hot-melt extruded formulation, of at least one polymeric carrier material selected from the group consisting of ethyl cellulose (EC), hydroxypropylmethyl cellulose (HPMC), alginate, chitosan, corn starch, potato starch, polyvinylpyrrolidon (PVP), polyvinylacetate (PVA), polylactic acid (PLA), poly(methacrylic acid-co-ethyl acrylate) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, and
(iii) up to about 40 wt-%, based on the total weight of the hot melt extruded formulation, of at least one plasticizer selected from the group consisting of ethylene glycol, 1,2-butylene glycol, 2,3-butylene glycol, styrene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, monopropylene glycol monoisopropyl ether, propylene glycol monoethyl ether, ethylene glycol monoethyl ether, diethylene glycol monoethyl ether, sorbitol lactate, ethyl lactate, butyl lactate, ethyl glycolate, dibutylsebacate, acetyltributylcitrate, triethyl citrate, acetyl triethyl citrate, tributyl citrate and allyl glycolate.

12. The hot-melt extrusion process according to claim 11 , which comprises conducting hot-melt extrusion of 5-20 wt-% of component (i), 80-95 wt-% of component (ii) and 10-40 wt-% of component (iii).

13. The hot-melt extrusion process according to claim 11 , which comprises conducting hot-melt extrusion of 5-10 wt-% or component (i), 90-95 wt-% of component (ii) and 10-40 wt-% of component (iii).

Assignees

• Dsm Ip Assets Bv

Inventors

• Teleki Alexandra
• Adler Camille

Classifications

• A61K31/015 Primary

  carbocyclic · CPC title

• A61K9/146

  with organic macromolecular compounds · CPC title

• A23P30/20 Primary

  Extruding · CPC title

• A23L29/035

  containing oxygen as heteroatom (gums A23L29/25; sugar or sugar alcohols A23L29/30) · CPC title

• A23K20/10 Primary

  Organic substances · CPC title