Orally disintegrating tablet compositions of lamotrigine
View Patent ↗The compositions of the present invention composition comprise a therapeutically effective amount of particles comprising lamotrigine, in combination with granules comprising a disintegrant, and a sugar alcohol and/or a saccharide. These compositions are useful in treating epilepsy and bipolar disorder, particularly for patients with dysphagia, and to improve compliance with bipolar patients.
1. An ODT composition consisting essentially of:
a therapeutically effective amount of lamotrigine microcapsules comprising 25 or 200 mg of lamotrigine crystals having an average particle size of about 1-50 μm, coated with a taste-masking layer;
a disintegrant; and
a sugar alcohol, a saccharide, or both a sugar alcohol and a saccharide;
wherein after a single oral administration said ODT composition provides:
a C max in the range of 0.276 to 0.482 ng/mL of lamotrigine,
an AUC 0-24 in the range of 4.87 to 8.17 ng·hr/mL of lamotrigine, or
both a C max in the range of 0.276 to 0.482 ng/mL of lamotrigine and an AUC 0-24 in the range of 4.87 to 8.17 ng·hr/mL of lamotrigine,
if the total amount of lamotrigine in the ODT is 25 mg, or
a C max in the range of 2.21 to 3.95 ng/mL of lamotrigine,
an AUC 0-24 in the range of 36.0 to 63.6 ng·hr/mL of lamotrigine, or
both a C max in the range of 2.21 to 3.95 ng/mL of lamotrigine and an AUC 0-24 in the range of 36.0 to 63.6 ng·hr/mL of lamotrigine,
if the total amount of lamotrigine in the ODT is 200 mg.
2. The ODT composition of claim 1 , wherein the disintegrant is selected from the group consisting of crospovidone, sodium starch glycolate, crosslinked sodium carboxymethyl cellulose, low substituted hydroxypropyl cellulose, and mixtures thereof.
3. The ODT composition of claim 1 , wherein the sugar alcohol is selected from the group consisting of arabitol, isomalt, erythritol, glycerol, lactitol, mannitol, sorbitol, xylitol, maltitol, and mixtures thereof.
4. The ODT composition of claim 1 , wherein the saccharide is selected from the group consisting of glucose, fructose, lactose, ribose, sucrose, maltose, trehalose, cellobiose, and mixtures thereof.
5. The ODT composition of claim 1 , wherein the ODT composition consists essentially of the lamotrigine microcapsules, the disintegrant, and a sugar alcohol, wherein the sugar alcohol is selected from the group consisting of arabitol, isomalt, erythritol, glycerol, lactitol, mannitol, sorbitol, xylitol, maltitol, and mixtures thereof.
6. The ODT composition of claim 2 consisting essentially of the lamotrigine microcapsules, the disintegrant, and a sugar alcohol, wherein the sugar alcohol is selected from the group consisting of arabitol, isomalt, erythritol, glycerol, lactitol, mannitol, sorbitol, xylitol, maltitol, and mixtures thereof.
7. The ODT composition of claim 1 , wherein the ODT composition consists essentially of the lamotrigine microcapsules, the disintegrant, and a saccharide, wherein the saccharide is selected from the group consisting of glucose, fructose, lactose, ribose, sucrose, maltose, trehalose, cellobiose, and mixtures thereof.
8. The ODT composition of claim 2 , wherein the ODT composition consists essentially of the lamotrigine microcapsules, the disintegrant, and a saccharide, wherein the saccharide is selected from the group consisting of glucose, fructose, lactose, ribose, sucrose, maltose, trehalose, cellobiose, and mixtures thereof.
9. The ODT composition of claim 1 , wherein the ODT composition substantially disintegrates within about 60 seconds after administration in the oral cavity of the patient.
10. The ODT composition of claim 9 , wherein the ODT composition substantially disintegrates within about 30 seconds after administration in the oral cavity of the patient.
11. The ODT composition of claim 1 , wherein the ODT composition disintegrates within about 30 seconds when tested by the <USP 701> Disintegration Test.
12. The ODT composition of claim 1 , wherein the ODT composition releases about 70% or more of the total dose of lamotrigine upon entering the stomach of a patient.
13. The ODT composition of claim 1 , further comprising additional pharmaceutically acceptable ingredients selected from the group consisting of a filler, a flavor, a sweetener, a colorant, and combinations thereof.
14. The ODT composition of claim 1 , wherein the ODT composition provides a C max in the range of 0.276 to 0.482 ng/mL of lamotrigine, if the total amount of lamotrigine in the ODT is 25 mg.
15. The ODT composition of claim 1 , wherein the ODT composition provides an AUC 0-24 in the range of 4.87 to 8.17 ng·hr/mL of lamotrigine, if the total amount of lamotrigine in the ODT is 25 mg.
16. The ODT composition of claim 1 , wherein the ODT composition provides a C max in the range of 0.276 to 0.482 ng/mL of lamotrigine and an AUC 0-24 in the range of 4.87 to 8.17 ng·hr/mL of lamotrigine, if the total amount of lamotrigine in the ODT is 25 mg.
17. The ODT composition of claim 1 , wherein the ODT composition provides a C max in the range of 2.21 to 3.95 ng/mL of lamotrigine, if the total amount of lamotrigine in the ODT is 200 mg.
18. The ODT composition of claim 1 , wherein the ODT composition provides an AUC 0-24 in the range of 36.0 to 63.6 ng·hr/mL of lamotrigine, if the total amount of lamotrigine in the ODT is 200 mg.
19. The ODT composition of claim 1 , wherein the ODT composition provides a C max in the range of 2.21 to 3.95 ng/mL of lamotrigine and an AUC 0-24 in the range of 36.0 to 63.6 ng·hr/mL of lamotrigine, if the total amount of lamotrigine in the ODT is 200 mg.
20. An ODT composition consisting essentially of:
a therapeutically effective amount of lamotrigine microcapsules comprising 25 or 200 mg of lamotrigine crystals having an average particle size of about 1-50 μm, coated with a taste-masking layer comprising a pharmaceutically acceptable water-insoluble polymer and a pharmaceutically acceptable water-soluble or gastro-soluble pore-former in a ratio of about 95/5 to about 50/50;
a disintegrant; and
a sugar alcohol, a saccharide, or both a sugar alcohol and a saccharide;
wherein after a single oral administration said ODT composition provides:
a C max in the range of 0.276 to 0.482 ng/mL of lamotrigine, an AUC 0-24 in the range of 4.87 to 8.17 ng·hr/mL of lamotrigine, or
both a C max in the range of 0.276 to 0.482 ng/mL of lamotrigine and an AUC 0-24 in the range of 4.87 to 8.17 ng·hr/mL of lamotrigine, if the total amount of lamotrigine in the ODT is 25 mg, or
a C max in the range of 2.21 to 3.95 ng/mL of lamotrigine, an AUC 0-24 in the range of 36.0 to 63.6 ng·hr/mL of lamotrigine, or
both a C max in the range of 2.21 to 3.95 ng/mL of lamotrigine and an AUC 0-24 in the range of 36.0 to 63.6 ng·hr/mL of lamotrigine, if the total amount of lamotrigine in the ODT is 200 mg; and
wherein the ODT composition releases about 70% or more of the total amount of lamotrigine in 30 min when tested for dissolution using United States Pharmacopeia Apparatus 2 (paddles@ 75 rpm in 900 mL of 0.01 N HCl buffer).