Gastroretentive drug formulation and delivery systems and their method of preparation using functionalized calcium carbonate

Patent metadata

Field	Value
Publication number	US-9993428-B2
Application number	US-201314429492-A
Country	US
Kind code	B2
Filing date	Oct 10, 2013
Priority date	Oct 12, 2012
Publication date	Jun 12, 2018
Grant date	Jun 12, 2018

Abstract

An instantly floating gastroretentive drug formulation comprising at least one functionalized natural and/or synthetic calcium carbonate-comprising mineral and at least one pharmaceutically active ingredient and at least one formulating aid wherein said functionalized natural or synthetic calcium carbonate is a reaction product of natural or synthetic calcium carbonate with carbon dioxide and one or more acids, wherein the carbon dioxide is formed in situ by the acid treatment and/or is supplied from an external source.

First claim

The invention claimed is:

1. An instantly floating gastroretentive formulation comprising at least one functionalized natural and/or synthetic calcium carbonate comprising pores containing air that promote flotation of the formulation in gastric fluid, at least one pharmaceutically active ingredient, and at least one film forming excipient, wherein the functionalized natural or synthetic calcium carbonate is a reaction product of natural or synthetic calcium carbonate with carbon dioxide and one or more acids, wherein the carbon dioxide is formed in situ by the acid treatment and/or is supplied from an external source, wherein the functionalized natural or synthetic calcium carbonate is made before the formulation is prepared, wherein the formulation comprises 30 to 95 weight percent of the at least one functionalized natural and/or synthetic calcium carbonate based on the total weight of the formulation, wherein the formulation comprises 1 to 60 wt % of the at least one film forming excipient based on the total weight of the formulation, and wherein the formulation prior to administration has a density that is below the density of gastric fluid.

2. The formulation according to claim 1 , wherein the functionalized calcium carbonate (FCC) is prepared from natural calcium carbonate selected from the group consisting of marble, calcite, chalk, limestone, dolomite, and any mixture thereof.

3. The formulation according to claim 1 , wherein the functionalized calcium carbonate (FCC) is prepared from synthetic calcium carbonate that is precipitated calcium carbonate (PCC) having one or more aragonitic, vateritic, prismatic, rhombohedral or scalenohedral forms.

4. The formulation according to claim 1 , wherein the one or more acids is selected from the group consisting of hydrochloric acid, sulfuric acid, sulfurous acid, hydrosulfate, phosphoric acid, phosphoric acid in combination with acetic, formic or citric acid or acid salts thereof, and any mixture thereof.

5. The formulation according to claim 1 , wherein the one or more acids is phosphoric acid.

6. The formulation according to claim 1 , wherein the functionalized natural or synthetic calcium carbonate has a BET specific surface area of from 5 m 2 /g to 200 m 2 /g, measured using nitrogen and the BET method according to ISO 9277:2010.

7. The formulation according to claim 1 , wherein the functionalized natural or synthetic calcium carbonate has a BET specific surface area of from 20 m 2 /g to 150 m 2 /g, measured using nitrogen and the BET method according to ISO 9277:2010.

8. The formulation according to claim 1 , wherein the functionalized natural or synthetic calcium carbonate has a BET specific surface area of from 40 m 2 /g to 100 m 2 /g, measured using nitrogen and the BET method according to ISO 9277:2010.

9. The formulation according to claim 1 , wherein the functionalized natural or synthetic calcium carbonate has a weight median grain diameter of from 0.1 to 50 μm, measured using Malvern Mastersizer X long bed.

10. The formulation according to claim 1 , wherein the functionalized natural or synthetic calcium carbonate has a weight median grain diameter of from 0.5 to 25 μm, measured using Malvern Mastersizer X long bed.

11. The formulation according to claim 1 , wherein the functionalized natural or synthetic calcium carbonate has a weight median grain diameter of from 0.8 to 20 μm, measured using Malvern Mastersizer X long bed.

12. The formulation according to claim 1 , wherein the functionalized natural or synthetic calcium carbonate has a weight median grain diameter of from 1 to 15 μm, measured using Malvern Mastersizer X long bed.

13. The formulation according to 36, wherein the least one pharmaceutically active ingredient is an active agent or an inactive precursor that is synthetic-, semi-synthetic or of natural origin or any combination thereof.

14. The formulation according to claim 1 , wherein the at least one film forming excipient is selected from the group consisting of hydrophilic film forming excipients, lipophilic film forming excipients, and any combination thereof.

15. The formulation according to claim 1 , wherein the at least one film forming excipient is a hydrophilic film forming excipient selected from group consisting of water soluble polyethylene glycols, polyethylene oxides, polypropylene glycols, polypropylene oxides or any combination thereof, polymers having a weight average molecular weight from 2,000 Da to 20,000,000 Da, chitosan, polymers of acrylic acid, polyvinylpyrrolidon, insoluble cross-linked polyvinylpyrollidones, homopolymers of N-vinyl-2-pyrrolidone, modified cellulose gums, starch glycolates, pregelatinized starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, alkyl-, hydroxyalkyl-, carboxyalkyl-cellulose esters, hydroxpropyl methyl cellulose phthalate, carboxymethylcellulose salts, alginates, ion exchange resins, gums, chitin, clays, gellan gum, crosslinked polacrillin copolymers, agar, gelatin, dextrines, shellac, and any combination thereof.

16. The formulation according to claim 1 , wherein the at least one film forming excipient is a lipophilic film forming excipient selected from the group consisting of hydrogenated vegetable, castor oils, mineral oils, waxes fatty acids and fatty acid salts with a carbon chain lengths from C6 to C20, being branched, un-branched, unsaturated, partially saturated, and any combination thereof, magnesium and/or calcium stearate, paraffin, cetyl alcohol, cetyl stearyl alcohol, glyceril monostearate, lanolin, lanolin alcohols, polyethylene glycol ethers of n-alkanols, polyoxyethylene castor oil derivates, polyoxyethylene sorbitan fatty acid esters, polyethylene stearates, sorbitan esters, stearyl alcohol, glycerol dibehenate, sodium stearyl fumarate, glycerol distearate, and any combination thereof.

17. The formulation according to claim 1 , further comprising a water soluble solid acid.

18. The formulation according to claim 17 , wherein the water soluble solid acid is selected from the group consisting of citric acid, fumaric acid, tartaric acid, malic acid, and any combination thereof.

19. A tablet, granule, capsule or pellet comprising the instantly floating gastroretentive formulation of claim 1 .

20. The formulation according to claim 1 , comprising 3 to 60 wt % of the least one film forming excipient based on the total weight of the formulation.

21. The formulation according to claim 1 , comprising 5 to 60 wt % of the least one film forming excipient based on the total weight of the formulation.

Assignees

• Omya Int Ag

Inventors

• Gerard Daniel E
• Schoelkopf Joachim
• Gane Patrick A C
• Eberle Veronika Anna
• Alles Rainer
• Puchkov Maxim
• Huwyler Jörg

Classifications

• A61K9/2013

  Organic compounds, e.g. phospholipids, fats · CPC title

• A61K9/1611 Primary

  Inorganic compounds · CPC title

• A61K9/2054

  Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose · CPC title

• A61K9/1641

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers · CPC title

• A61K9/1652

  Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin (homeopathic globules A61K9/1623) · CPC title