Rapid disperse dosage form
A high dose rapidly dispersing three-dimensionally printed dosage form comprising a high dose of water soluble drug in a porous matrix that disperses in water within a period of less than about 15 seconds is disclosed. Also disclosed are methods of preparing the dosage form and of treating a condition, disease or disorder that is therapeutically responsive to the drug.
1. A rapidly dispersible solid dosage form comprising a three-dimensionally-printed, porous, uncompressed and bound matrix, the matrix comprising 50-80% wt of water soluble drug, 3-35% wt of a disintegrant selected from the group consisting of microcrystalline cellulose (MCC), cross-linked polyvinylpyrrolidone, croscarmellose, sodium starch glycolate, and a combination thereof, glycerin in an amount ranging from 0.05-5% by weight of the matrix, and 0.5-20% wt of water soluble, aqueous fluid soluble, partially water soluble or partially aqueous fluid soluble binder, wherein the matrix comprises particles bound by at least one of the binder and the water-soluble drug, wherein the matrix disperses in about 15 sec or less in a volume of about 15 ml or less of water or saliva, and wherein the matrix has sufficient hardness to endure handling and storage.
2. The dosage form of claim 1 , wherein the matrix further comprises 0.005 to about 5.0% wt of antioxidant.
3. The dosage form of claim 1 , wherein the matrix comprises 0.1% or less of an oxidative degradant of the drug after being stored at 21° C. for six months at 75% RH.
4. The dosage form of claim 1 . wherein the matrix comprises an interior and an exterior and the exterior of the matrix is harder than the interior of the matrix.
5. The dosage form of claim 2 , wherein:
the matrix further comprises one or more surfactants, and optionally one or more of the following: one or more glidants, one or more flavorants, and one or more preservatives.
6. The dosage form of claim 5 wherein a) the one or more surfactant is present in an amount ranging from about 0.05 to about 1% wt based upon the final weight of the dosage form; b) the one or more antioxidant is present in an amount ranging from 0.005 to about 5.0% wt based upon the final weight of the dosage form; c) the one or more glidants is present in an amount ranging from about 0.1 to about 2.0% wt, based upon the final weight of the dosage form; and d) the matrix comprises about 250 to about 1000 mg of the drug.
7. The dosage form of claim 1 , wherein the dosage form comprises the 60-70% wt of the water soluble drug, 20-25% wt of the disintegrant, 10-15% wt of the binder, 0.5-2% wt sweetener, 0.1-1.5% wt glidant, 0.1-5% wt of the glycerin, 0.05-1.5% wt surfactant, and 0-0.5% wt flavor, wherein the binder is water soluble, aqueous fluid soluble, partially water soluble or partially aqueous fluid soluble.
8. The dosage form of claim 1 , wherein the hardness of the matrix ranges from about 2 to about 6 kp.
9. The dosage form of claim 1 , wherein the dosage form is preservative free.
10. The dosage form of claim 1 , wherein the dosage form has a shelf-life of at least one year.
11. The dosage form of claim 1 , wherein the matrix comprises about 250 mg to about 1000 mg of the drug.
12. The dosage form of claim 1 , wherein the dosage form comprises not more than 10% wt and not less 0.1% moisture as determined by loss on drying at 120° C.
13. The dosage form of claim 1 , wherein the drug is present in a form selected from the group consisting of hydrate, hemi-hydrate, crystalline, amorphous, anhydrate or a combination thereof.
14. The dosage form of claim 5 , wherein the matrix comprises an interior and an exterior and the exterior of the matrix is harder than the interior of the matrix.
15. The dosage form of claim 1 , wherein the hardness of the matrix ranges from about 3 to about 9 kp.
16. The dosage form of claim 1 , wherein the binder is introduced into the bound matrix by way of printing fluid used to form the matrix.
17. The dosage form of claim 1 , wherein the binder is introduced into the bound matrix by way of bulk powder used to form the matrix.
18. The dosage form of claim 1 , wherein the bound matrix comprises 15 to 50 printed incremental layers and the thickness of an incremental layer ranges from 0.008 to 0.012 inches.
19. The dosage form of claim 1 , wherein the dosage form has a diameter ranging from 13-14 mm to about 20-25 mm and a height ranging from 5-6 mm to about 8-10 mm.