Use of a matrix for orally administering sustained release magnesium, and composition containing said matrix

• US 8,399,017 B2
• Filed: 05/20/2009
• Issued: 03/19/2013
• Est. Priority Date: 05/20/2008
• Status: Active Grant

• Current Assignee: Fabienne Joanny
• Original Assignee: Fabienne Joanny
• Inventors: Joanny, Fabienne
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): YOUNG, MICAH PAUL
• Application Number:
  US12/993,678
• Publication Number:
  US 20110091548A1
• Time in Patent Office: 1,399 Days
• Field of Search: 424464-489
• US Class Current: 424/480
• CPC Class Codes: A61K 33/06 Aluminium, calcium or magnesium; Compounds thereof , e.g. clay
• CPC Class Codes: A61K 36/02 Algae
• CPC Class Codes: A61K 36/15 Pinaceae (Pine family), e.g. pine or cedar
• CPC Class Codes: A61K 36/42 Cucurbitaceae (Cucumber family)
• CPC Class Codes: A61K 36/53 Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
• CPC Class Codes: A61K 36/73 Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
• CPC Class Codes: A61K 36/84 Valerianaceae (Valerian family), e.g. valerian
• CPC Class Codes: A61K 36/899 Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/286 Polysaccharides, e.g. gums; Cyclodextrin
• CPC Class Codes: A61K 9/2886 having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer of the type active core-drug layer-inactive layer A61K9/209
• CPC Class Codes: A61K 9/7015 Drug-containing film-forming compositions, e.g. spray-on
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A tablet for oral administration comprises a matrix of progressive and continuous released magnesium. For the administration of 90 to 110 parts by weight of magnesium, the matrix comprises 180 to 190 parts by weight of hydroxypropylmethylcellulose, 19.8 to 22.2 parts by weight of glyceryl behenate, 10 to 12 parts by weight of lactose and 10 to 12 parts by weight of colloidal silica. A non-enteric protective coating that slows down the gastric dissolution of the magnesium may comprise 15 to 75 parts by weight of shellac, cellulose ether or a mixture thereof. The tablet may be administered to patients in need thereof.

Claims

1. A composition for oral administration, in tablet form, of magnesium with progressive release, comprising:

a matrix constituting a core comprising

(A) 90 to 110 parts by weight of magnesium, the source of magnesium being MgCl₂.9/2H₂O,

(B1) 180 to 190 parts by weight of hydroxypropylmethylcellulose,

(B2) 19.8 to 22.2 parts by weight of glyceryl behenate,

(C1) 10 to 12 parts by weight of lactose, and

(C2) 10 to 12 parts by weight of colloidal silica; and

a film coating of

(D) 15 to 75 parts by weight of a substance selected from shellac, cellulose ethers and mixtures thereof,

wherein the composition exhibits, in vitro after 2 h in a 0.1N HCl medium, a rate of dissolution (δ

) of the magnesium comprised therein of greater than or equal to 20% and less than or equal to 60%.

2. The composition according to claim 1, wherein said coating is one of:

(a) a single-layer film coating of shellac, and

(b) a two-layer film coating, each layer comprising a substance selected from shellac, cellulose ethers and mixtures thereof.

3. The composition according to claim 1, wherein, by determination in vitro in accordance with a dissolution system comprising first treating said composition in a 0.1N HCl medium from T=0 to T=2 h, and then treating it in a buffer at pH 6.8 from T=2 h to T=8 h, the composition exhibits an Mg dissolution rate (δ

), relative to the Mg administered, such that

at T=4 h, δ

is less than or equal to 85%;

at T=6 h, δ

is less than or equal to 98%; and

at T=8 h, δ

is less than or equal to 100%.

4. The composition according to claim 3, wherein the composition exhibits an Mg dissolution rate (δ

), relative to the Mg administered, such that

at T=4 h, δ

is greater than or equal to 40%;

at T=6 h, δ

is greater than or equal to 60%; and

at T=8 h, δ

is greater than or equal to 90%.

5. The composition according to claim 4, wherein the composition exhibits an Mg dissolution rate (δ

), relative to the Mg administered, such that

at T=2 h, δ

is between 25-58%;

at T=4 h, δ

is between 45-82%;

at T=6 h, δ

is between 80-95%; and

at T=8 h, δ

is between 95-99.9%.

6. The composition according to claim 5, wherein the film coating comprises 15-45 parts by weight of a substance selected from shellac, cellulose ether and a mixture thereof.

7. The composition according to claim 6, wherein the cellulose ether is at least one of hydroxypropylmethylcellulose and hydroxypropylcellulose.

8. The composition according to claim 7, wherein the film coating is one of:

(a) a single-layer film coating of shellac, and

(b) a two-layer film coating, each layer comprising a substance selected from shellac, cellulose ethers and mixtures thereof.

9. A method comprising:

orally administering, in tablet form, a therapeutically or cosmetically effective amount of a progressive release magnesium composition to a patient in need thereof, wherein the composition comprises;

a matrix constituting a core containing, for administration of 90 to 110 parts by weight of magnesium, the source of magnesium being MgCl₂.9/2H₂O, the following additional ingredients;

180 to 190 parts by weight of hydroxypropylmethylcellulose, 19.8 to 22.2 parts by weight of glyceryl behenate, 10 to 12 parts by weight of lactose and 10 to 12 parts by weight of colloidal silica, and

a protective coating that slows down gastric dissolution of the magnesium,

wherein the composition exhibits, in vitro after 2 h in a 0.1N HCl medium, a rate of dissolution (δ

) of the magnesium comprised therein of greater than or equal to 20% and less than or equal to 60%.

10. The method according to claim 9, wherein the coating constitutes 1.3% to 7.5% by weight relative to the weight of the matrix.

11. The method according to claim 9, wherein the coating is one of:

(a) a single-layer film coating of shellac, and

(b) a two-layer film coating, each layer comprising a substance selected from shellac, cellulose ethers and mixtures thereof.

12. The method according to claim 9, wherein the composition is administered as a food supplement.

13. The method according to claim 9, wherein the composition is administered as a cosmetic for at least one of:

moisturizing skin and treating or preventing stress of the skin.

14. A progressive release magnesium tablet for oral administration, comprising:

a matrix constituting a core containing a mixture of

90 to 110 parts by weight of magnesium, the source of magnesium being MgCl₂.9/2H₂O,

180 to 190 parts by weight of hydroxypropylmethylcellulose,

19.8 to 22.2 parts by weight of glyceryl behenate,

10 to 12 parts by weight of lactose, and

10 to 12 parts by weight of colloidal silica; and

a film coating containing 15 to 75 parts by weight of a substance selected from shellac, cellulose ethers and a mixture thereof,

wherein the tablet exhibits, in vitro after 2 h in a 0.1N HCl medium, a rate of dissolution (δ

) of the magnesium comprised therein of greater than or equal to 20% and less than or equal to 60%.

15. The tablet according to claim 14, wherein the coating is one of:

(a) a single-layer film coating of shellac, and

(b) a two-layer film coating, each layer comprising a substance selected from shellac, cellulose ether and a mixture thereof.

16. The tablet according to claim 15, wherein, by determination in vitro in accordance with a dissolution system comprising first treating said composition in a 0.1N HCl medium from T=0 to T=2 h, and then treating it in a buffer at pH 6.8 from T=2 h to T=8 h, the tablet exhibits an Mg dissolution rate (δ

), relative to the Mg administered, such that;

at T=2 h, δ

is between 25-58%;

at T=4 h, δ

is between 45-82%;

at T=6 h, δ

is between 80-95%; and

at T=8 h, δ

is between 95-99.9%.

17. The tablet according to claim 14, wherein the coating comprises an inner layer comprised of shellac and an outer layer comprised of a mixture of alkylcelluloses.

18. The tablet according to claim 17, wherein the mixture of alkylcelluloses comprises hydroxypropylmethylcellulose and hydroxypropylcellulose.

19. The tablet according to claim 14, wherein the film coating is 15 to 45 parts by weight.