Immediate release dosage form
An improved immediate release solid dosage form of naproxen with a certain particle size distribution for the intragranular portion, and a certain particle size distribution for the carbonate portion that allows naproxen to remain in solution and achieves fast dissolution and fast absorption of naproxen. The invention provides a naproxen dosage form that when administered to a human in a fasted state provides an average blood plasma naproxen concentration of at least 15-20 μg/ml in 10 minutes or less. The invention also provides a naproxen dosage form that when administered to a human in a fed state provides an average blood plasma naproxen concentration of at least 15-20 μg/ml in 50 minutes or less.
1. An immediate release solid dosage form comprising an intragranular portion and a carbonate portion, wherein the intragranular portion comprises 220 mg naproxen sodium, as well as compression filler, binder and disintegrant, wherein the carbonate portion comprises an effective amount of soluble carbonate at a particle size from about 50 microns to 200 microns so as to raise the pH and facilitate dissolution and absorption of the naproxen sodium to begin in a human's stomach in a fasted state, wherein the particle size of the intragranular portion is from about 200 microns to 400 microns, wherein the immediate release solid dosage form provides a blood plasma naproxen concentration of at least 15-20 μg/ml in 10 minutes or less, and wherein the solid dosage form does not include any other drug besides naproxen sodium.
2. The immediate release solid dosage form of claim 1 wherein the soluble carbonate is selected from the group consisting of sodium carbonate, sodium bicarbonate, calcium carbonate, magnesium carbonate, ammonium carbonate, ammonium bicarbonate, potassium bicarbonate, sodium glycine carbonate, disodium glycine carbonate, arginine carbonate and lysine carbonate.
3. The immediate release solid dosage form of claim 1 wherein the particle size of the soluble carbonate is from about 75 microns to 100 microns.
4. The immediate release solid dosage form of claim 1 wherein the amount of soluble carbonate present in the dosage form is from about 300 mg to 500 mg.
5. The immediate release solid dosage form of claim 1 wherein at least 50% of the naproxen sodium is dissolved from the immediate release solid dosage form within 300 seconds in USP dissolution apparatus 2 with 900 mL 0.0033 N hydrochloric acid at 30 rpm and 37° C.
6. The immediate release solid dosage form of claim 1 wherein at least 50% of the naproxen sodium is dissolved from the immediate release solid dosage form within 300 seconds in USP dissolution apparatus 2 with 900 mL of pH 7.4 phosphate buffer at 50 rpm and 37° C.
7. The immediate release solid dosage form of claim 1 wherein at least 75% of the naproxen sodium is dissolved from the immediate release solid dosage form within 600 seconds in USP dissolution apparatus 2 with 900 mL of pH 7.4 phosphate buffer at 50 rpm and 37° C.
8. The immediate release solid dosage form of claim 6 wherein the particle size of the intragranular portion is from about 200 microns to 300 microns.
9. The immediate release solid dosage form of claim 6 wherein the bulk density of the intragranular portion is from about 0.5 g/cc to about 0.9 g/cc.
10. The immediate release solid dosage form of claim 1 wherein the dosage form has a hardness of from about 10 kiloponds to about 17 kiloponds.