Pharmaceutical composition containing lamotrigine particles of defined morphology

• US 20050238724A1
• Filed: 04/23/2003
• Published: 10/27/2005
• Est. Priority Date: 04/23/2002
• Status: Abandoned Application

• Current Assignee: Teva Pharmaceuticals USA, Inc. (Teva Pharmaceutical Industries Limited)
• Original Assignee: Teva Pharmaceutical Industries Limited
• Inventors: Aronhime, Judith, Samburski, Guy
• Application Number:
  US10/511,987
• Publication Number:
  US 20050238724A1
• Time in Patent Office: Days
• US Class Current: 424/489
• CPC Class Codes: A61K 31/53 having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine melarsoprol A61K31/555 ; with four nitrogen atoms A61K31/495
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• 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 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51

Abstract

The present invention provides a pharmaceutical composition comprising a plurality of lamotrigine particles having a specific surface area of from about two to about three and a half meters per gram. Pharmaceutical compositions falling within the surface area criteria for the lamotrigine particles include those having a particle diameter equal to or less than about 100 μm, preferably about 50 μm, and most preferably 10 μm. The pharmaceutical composition can be formulated into a wide variety of dosage forms.

Claims

1. A plurality of lamotrigine particles having a specific surface area of from about two to about three and a half square meters per gram.

2. The plurality of lamotrigine particles of claim 1 having a specific surface area of about three square meters per gram.

3. The plurality of lamotrigine particles of claim 1 wherein the diameter of all particles in the plurality is equal to or less than about 100 μ

m.

4. The plurality of lamotrigine particles of claim 3 wherein the diameter of all particles in the plurality is equal to or less than about 50 μ

m.

5. The plurality of lamotrigine particles of claim 4 wherein the diameter of all particles in the plurality is equal to or less than about 10 μ

m.

6. A pharmaceutical composition comprising a plurality of lamotrigine particles having a specific surface area of from about two to about three and a half square meters per gram.

7. The pharmaceutical composition of claim 6 having a specific surface area of about three square meters per gram.

8. The pharmaceutical composition of claim 6 wherein the diameter of all particles in the plurality is equal to or less than about 100 μ

m.

9. The pharmaceutical composition of claim 8 wherein the diameter of all particles in the plurality is equal to or less than about 50 μ

m.

10. The pharmaceutical composition of claim 9 wherein the diameter of all particles in the plurality is equal to or less than about 10 μ

m.

11. A dosage form comprising the pharmaceutical composition of claim 6.

12. The dosage form of claim 11 that is a solid oral dosage.

13. The solid oral dosage of claim 12 wherein the pharmaceutical composition comprises at least one pharmaceutically acceptable excipient.

14. The solid oral dosage form of claim 13 wherein the pharmaceutically acceptable excipient is selected from the group consisting of microcrystalline cellulose, microfine cellulose, lactose, starch, pregelatinized starch, calcium carbonate, calcium sulfate, sugar, dextrates, dextrin, dextrose, dibasic calcium phosphate dihydrate, tribasic calcium phosphate, kaolin, magnesium carbonate, magnesium oxide, maltodextrin, mannitol, polymethacrylate, potassium chloride, powdered cellulose, sodium chloride, sorbitol, talc, acacia, alginic acid, carbomer, carboxymethylcellulose sodium, dextrin, ethyl cellulose, gelatin, guar gum, hydrogenated vegetable oil, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, liquid glucose, magnesium aluminum silicate, maltodextrin, methylcellulose, polymethacrylates, povidone, pregelatinized starch, sodium alginate, starch, alginic acid, carboxymethyl cellulose calcium, colloidal silicon dioxide, croscarmellose sodium, crospovidone, guar gum, magnesium aluminum silicate, methyl cellulose, polacrilin potassium, powdered cellulose, pregelatinized starch, sodium alginate and sodium starch glycolate.

15. The solid oral dosage form of claim 12 containing a unit dose of from about 100 to about 400 milligrams of lamotrigine.

16. The dosage form of claim 11 that is a liquid oral dosage.

17. The liquid oral dosage of claim 16 wherein the liquid oral dosage comprises a liquid carrier selected from the group consisting of water, vegetable oil, alcohol, polyethylene glycol, propylene glycol and glycerin.

18. The liquid oral dosage of claim 17 wherein the liquid carrier is water.

19. The liquid oral dosage of claim 16 further comprising at least one excipient selected from the group consisting of gelatin, egg yolk, casein, cholesterol, acacia, tragacanth, chondrus, pectin, methyl cellulose, carbomer, cetostearyl alcohol, cetyl alcohol, alginic acid bentonite, carbomer, carboxymethylcellulose calcium or sodium, ethylcellulose, gelatin guar gum, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, maltodextrin, polyvinyl alcohol, povidone, propylene carbonate, propylene glycol alginate, sodium alginate, sodium starch glycolate, starch tragacanth, xanthan gum, sorbitol, saccharin, sodium saccharin, sucrose, aspartame, fructose, mannitol, invert sugar;

ethyl alcohol, sodium benzoate, butylated hydroxy toluene, butylated hydroxyanisole, ethylenediamine tetraacetic acid, guconic acid, lactic acid, citric acid, acetic acid, sodium guconate, sodium lactate, sodium citrate and sodium acetate.

20. The dosage form of claim 11 that is a liquid parenteral dosage.

21. The liquid parenteral dosage of claim 20 further comprising a tonicity modifier.

22. The liquid parenteral dosage of claim 21 wherein the tonicity modifier is dextrose.

23. The liquid parenteral dosage of claim 22 wherein the dextrose is a 5% solution of dextrose.

24. The liquid parenteral dosage of claim 20 further comprising at least one excipient selected from the group consisting of dextrose, glycerol, lactose, mannitol, sorbitol, acetate, citrate, tartrate, parabens, 1,6-dialkyl substituted phenols, benzalkonium chloride, benzethonium chloride, benzyl alcohol, sodium benzoate, chlorobutanol, phenethyl alcohol, sodium bisulfite, sodium metabisulfite and tocopherol.

25. A method of reducing the incidence of seizures in a patient comprising the step of administering a dosage form of any of claims 12, 16 and 20.

26. The method of claim 25 wherein the dosage form is administered in adjunct with another seizure inhibiting drug.