Pharmaceutical multiple unit particulate formulation in the form of coated cores

• US 5,958,458 A
• Filed: 08/01/1995
• Issued: 09/28/1999
• Est. Priority Date: 06/15/1994
• Status: Expired due to Term

• Current Assignee: Actavis Group (Abbvie Incorporated)
• Original Assignee: A/S Dumex
• Inventors: Jensen, Lone Norgaard, Norling, Tomas, Hansen, Jens
• Primary Examiner(s): Webman, Edward J.
• Application Number:
  US08/509,107
• Time in Patent Office: 1,519 Days
• Field of Search: 424/422, 424/458-462, 424/469-470, 424/489-502, 424/421, 424/687, 424/466, 424/471, 514/951, 514/952
• US Class Current: 424/490
• CPC Class Codes: A61K 9/0007 Effervescent A61K9/0065 takes precedence
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61K 9/1611 Inorganic compounds
• CPC Class Codes: A61K 9/1676 having a drug-free core with discrete complete coating layer containing drug adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50
• CPC Class Codes: A61K 9/5015 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5047 Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5078 with drug-free core

Abstract

A pharmaceutical multiple unit particulate formulation in the form of coated cores which includes a pharmaceutically acceptable carrier selected from calcium carbonate, calcium silicate, calcium magnesium silicate, calcium phosphate, kaolin, sodium hydrogen carbonate, sodium sulfate, barium carbonate, barium sulfate, magnesium sulfate, magnesium carbonate, and activated carbon, and an active substance in a layer on the outer surface of the cores.

Claims

1. A pharmaceutical multiple unit particulate formulation comprising individual units in the form of coated cores, wherein at least 50% w/w of the cores before coating have a particle size within a range of about 90-225 μ

m, when tested as described herein, each coated core comprising

i) a pharmaceutically acceptable inert carrier which is present in the core in a first concentration of at least about 20% w/w calculated on the total weight of the core, and which is selected from the group consisting of calcium carbonate, calcium silicate, calcium magnesium silicate, calcium phosphate, kaolin, sodium hydrogen carbonate, sodium sulfate, barium carbonate, barium sulfate, magnesium sulfate, magnesium carbonate, and activated carbon, and

ii) an active drug substance being present in a layer on the outer surface of the cores,

the pharmaceutically acceptable inert carrier being such a material which--when formulated into uncoated cores containing the pharmaceutically acceptable inert carrier optionally in combination with a binder and with a second concentration of the inert carrier of at least 80% w/w calculated on the total weight of the uncoated core--has a friability (weight loss in % w/w) of at the most about 20%, when tested as described herein, and the cores have a flow angle--when tested according to method A described herein using a diameter of the disc outlet of 9 mm--of at the most 30°

.

2. A pharmaceutical particulate formulation according to claim 1, wherein the second concentration of the pharmaceutically acceptable inert carrier in said uncoated cores containing the inert carrier optionally in combination with a binder is at least 85% w/w, calculated on the total weight of the uncoated core.

3. A pharmaceutical particulate formulation according to claim 1, wherein said uncoated cores containing the inert carrier optionally in combination with a binder have a friability (weight loss in % w/w) of at the most about 15%, when tested as described herein.

4. A pharmaceutical particulate formulation according to claim 1, wherein the first concentration of the inert carriers is at least about 50% w/w.

5. A pharmaceutical particulate formulation according to claim 4, wherein at least 50% w/w of the cores before coating have a particle size within a range of about 90-225 μ

m, when tested as described herein.

6. A pharmaceutical particulate formulation according to claim 1, wherein at least 70% w/w of the cores before coating have a particle size within the range of about 90-225 μ

m, when tested as described herein.

7. A pharmaceutical particulate formulation according to claim 1, wherein at least 50% w/w of the cores before coating have a particle size of at the most 180 μ

m, when tested as described herein.

8. A pharmaceutical particulate formulation according to claim 1, wherein the pharmaceutically acceptable inert carrier and the active substance are in admixture.

9. A pharmaceutical particulate formulation according to claim 1, wherein the coating on the cores is selected from the group consisting of modified release coatings, film coatings, bioadhesive coatings, and sugar coatings.

10. A pharmaceutical particulate formulation according to claim, 1, wherein the inert carrier is calcium carbonate.

11. A pharmaceutical particulate formulation according to claim, 1, further comprising a pharmaceutically acceptable excipient.

12. A pharmaceutical particulate formulation according to claim 11 wherein the pharmaceutically acceptable excipient is selected from the group consisting of fillers, binders, disintegrants, glidants, and lubricants.

13. A pharmaceutical formulation according to claim 1, adapted for oral, buccal, mucosal, nasal, rectal, topical, or wound administration.

14. A solid dosage form comprising a pharmaceutical particulate formulation according to claim 13.

15. A solid dosage form according to claim 14 in unit dosage form.

16. A solid dosage form according to claim 14, wherein the unit dosage form is selected from the group consisting of tablets, capsules, effervescent tablets, chewable tablets, lozenges, immediate release tablets, modified release tablets, suppositories, vagitories, implants, and plasters.

17. A solid dosage form according to claim 14 adapted for oral, buccal, mucosal, nasal, rectal, vaginal, or topical administration, or administration to wounds.

18. A solid dosage form according to claim 14 which is coated with a coating selected from the group consisting of a film coating, a sugar coating, a bioadhesive coating, and a modified release coating.

19. A pharmaceutical multiple unit particulate formulation comprising individual units in the form of coated cores, wherein at least 50% w/w or the cores before coating have a particle size within a range of about 90-225 μ

m, when tested as described herein, each coated core comprising

i) a pharmaceutically acceptable inert carrier which is present in the core in a first concentration of at least about 20% w/w calculated on the total weight of the core, and which is selected from the group consisting of calcium carbonate, calcium silicate, calcium magnesium silicate, calcium phosphate, kaolin, sodium hydrogen carbonate, sodium sulfate, barium carbonate, barium sulfate, magnesium sulfate, magnesium carbonate, and activated carbon, and

ii) an active drug substance,

the pharmaceutically acceptable inert carrier being such a material which--when formulated into uncoated cores containing the pharmaceutically acceptable inert carrier optionally in combination with a binder and with a second concentration of the inert carrier of at least 80% w/w calculated on the total weight of the uncoated core--has a friability (weight loss in % w/w) of at the most about 20%, when tested as described herein, and the cores have a flow angle--when tested according to method A described herein using a diameter of the disc outlet of 9 mm--of at the most 30°

, and

the coating of the coated cores comprising a first and a second layer, the first layer comprising the active drug substance.

20. A pharmaceutical multiple unit particulate formulation comprising individual units in the form of coated cores, wherein at least 50% w/w of the cores before coating have a particle size of at the most 250 μ

m, when tested as described herein, each coated core comprising

i) a pharmaceutically acceptable inert carrier which is present in the core in a first concentration of at least about 20% w/w calculated on the total weight of the core, and which is selected from the group consisting of calcium carbonate, calcium silicate, calcium magnesium silicate, calcium phosphate, kaolin, sodium sulfate, barium carbonate, barium sulfate, magnesium sulfate, magnesium carbonate, and activated carbon, and

ii) an active drug substance,

the pharmaceutically acceptable inert carrier being such a material which--when formulated into uncoated cores containing the pharmaceutically acceptable inert carrier optionally in combination with a binder and with a second concentration of the inert carrier of at least 80% w/w calculated on the total weight of the uncoated core--has a friability (weight loss in % w/w) of at the most about 20%, when tested as described herein, and the cores have a flow angle--when tested according to method A described herein using a diameter of the disc outlet of 9 mm--of at the most 30°

, and

the coating of the coated cores comprising a first and a second layer, the second layer comprising the active drug substance.