Immediate release dosage forms containing solid drug dispersions
View Patent ↗High loading immediate release dosage forms containing at least 30 wt % of a solid drug dispersion, at least 5 wt % of a disintegrant and a porosigen are disclosed that exhibit excellent strength and aqueous solubility.
1. A high-loading immediate release dosage form comprising:
an immediate release, disintegrable, compressed blend dosage form, comprising
(a) at least 50 wt % of a solid amorphous dispersion, said dispersion comprising a low solubility drug and a concentration-enhancing polymer selected from the group consisting of hydroxypropyl methyl cellulose acetate succinate, hydroxypropyl methyl cellulose phthalate, cellulose acetate phthalate, cellulose acetate trimellitate, carboxymethyl ethyl cellulose, and blends thereof, wherein the amount of drug in crystalline form in said dispersion does not exceed 10 wt %, said polymer being present in said dispersion in an amount of a drug-to-polymer weight ratio greater than 0.05 and less than 2.5,
(b) at least 5 wt % of a disintegrant, and
(c) a porosigen,
wherein said immediate release dosage form has a porosity of at least 0.15, and disintegrates in 10 minutes or less following introduction to an in vitro disintegration medium of deionized water at 37° C.
2. The dosage form of claim 1 wherein said porosigen is present in an amount of at least 10 wt %.
3. The dosage form of claim 1 or 2 wherein said porosigen is selected from the group consisting of microcrystalline cellulose, dibasic calcium phosphate anhydrous, dibasic calcium phosphate dihydrate, tribasic calcium phosphate, monobasic sodium phosphate, dibasic sodium phosphate, calcium carbonate, calcium sulfate dihydrate, calcium sulfate, silicon dioxide, magnesium aluminum silicate, magnesium carbonate, and mixtures thereof.
4. The dosage form of claim 3 wherein said porosigen is selected from the group consisting of dibasic calcium phosphate anhydrous and dibasic calcium phosphate dihydrate.
5. The dosage form of claim 1 or 2 wherein said disintegrant is selected from the group consisting of crospovidone, croscarmellose sodium, lower alkyl-substituted hydroxypropyl cellulose, methyl cellulose, polacrilin potassium, sodium starch glycolate, and mixtures thereof.
6. The dosage form of claim 5 wherein said disintegrant is selected from the group consisting of crospovidone, croscarmellose sodium, and mixtures thereof.
7. The dosage form of claim 1 wherein said dosage form comprises 5 to 20 wt % of said disintegrant.
8. The dosage form of claim 7 wherein said disintegrant is crospovidone and said porosigen is dibasic calcium phosphate anhydrous.
9. The dosage form of claim 1 or 2 further comprising a coating.
10. The dosage form of claim 1 wherein the blend is a tablet having a strength of at least 5 Kp/cm 2 , a porosity of at least 0.15, or both.
11. The dosage form of claim 1 consisting essentially of the immediate release, disintegrable, compressed blend dosage form, which consists essentially of the solid amorphous dispersion, the disintegrant, and the porosigen.
12. The high-loading immediate release dosage form of claim 1 wherein the compressed blend comprises granules with a mean granule size of about 100 μm to 400 μm.
13. A high-loading immediate release dosage form comprising:
an immediate release, disintegrable, compressed blend dosage form, comprising
(a) at least 50 wt % of a solid amorphous dispersion, said dispersion comprising a low solubility drug and a concentration-enhancing polymer selected from the group consisting of hydroxypropyl methyl cellulose acetate succinate, hydroxypropyl methyl cellulose phthalate, cellulose acetate phthalate, cellulose acetate trimellitate, carboxymethyl ethyl cellulose, and blends thereof, wherein the amount of drug in crystalline form in said dispersion does not exceed 10 wt %, said polymer being present in said dispersion in an amount of a drug-to-polymer weight ratio greater than 0.05 and less than 2.5,
(b) at least 5 wt % of a disintegrant, and
(c) a porosigen; and
(d) an enteric coating comprising a pH-sensitive polymer that is soluble or disintegrable at the pH of the duodenum and small intestine,
wherein the compressed blend comprises granules with a mean granule size of about 100 μm to 400 μm, wherein said immediate release dosage form has a porosity of at least 0.15, and wherein the high-loading immediate release dosage form releases at least 70 wt % of the low solubility drug in 15 minutes following introduction to an in vitro dissolution medium comprising phosphate-buffered saline or model fasted duodenal solution at 37° C.
14. The high-loading immediate release dosage form of claim 1 , wherein the immediate release dosage form has a porosity of at least 0.20.
15. The high-loading immediate release dosage form of claim 1 , wherein the immediate release dosage form has a porosity of at least 0.25.
16. The high-loading immediate release dosage form of claim 1 , wherein the immediate release dosage form releases at least 70 wt % of the low solubility drug within 15 minutes following introduction to the disintegration medium.