Matrix-based pulse release pharmaceutical formulation
View Patent ↗The present invention relates to an oral pulse release pharmaceutical composition, which comprises a polymer matrix core, wherein at least one pharmaceutically active ingredient is distributed within the core and on the outer surface of the core. Amphetamine salts, among a number of other pharmaceutically active ingredients, can be formulated as a pharmaceutical composition described herein. The present invention also provides a method for preparing an immediate release component on a solid pharmaceutical formulation.
1. An oral pharmaceutical composition consisting of (i) a polymer matrix consisting of a mixture of at least one enteric polymer, at least one sustained release polymer, an optional plasticizer, an optional binder, and a first pharmaceutically active ingredient distributed substantially uniformly throughout the polymer matrix, and (ii) a population of discrete particles adhering to the outer surface of the polymer matrix, the population of discrete particles consisting of a second pharmaceutically active ingredient and having a size from about 500 nanometers to about 800 microns, wherein the oral pharmaceutical composition has a pulse release profile.
2. The oral pharmaceutical composition of claim 1 wherein the first and second pharmaceutically active ingredients are the same.
3. The oral pharmaceutical composition of claim 1 , wherein the discrete particles adhering to the outer surface of the polymer matrix range from about 50 microns to about 200 microns.
4. The oral pharmaceutical composition of claim 1 , wherein the at least one enteric polymer is present in an amount from about 30% w/w to about 80% w/w of the polymer matrix.
5. The oral pharmaceutical composition of claim 4 , wherein the amount of the at least one enteric polymer is about 55% w/w of the polymer matrix.
6. The oral pharmaceutical composition of claim 1 , wherein the at least one sustained release polymer is present in an amount from about 5% w/w to about 80% w/w of the polymer matrix.
7. The oral pharmaceutical composition of claim 6 , wherein the amount of the at least one sustained release polymer is about 5% w/w of the polymer matrix.
8. The oral pharmaceutical composition of claim 1 , wherein the at least one enteric polymer is selected from the group consisting of hydroxypropyl methylcellulose acetate succinate (HPMCAS), hydroxypropyl methylcellulose phthalate (HPMCP), polyvinyl acetate phthalate, cellulose acetate phthalate, cellulose acetate trimellitate, shellac, polymethacrylates containing carboxyl groups, amylose acetate phthalate, styrene maleic acid copolymer, cellulose acetate succinate, and combinations thereof.
9. The oral pharmaceutical composition of claim 8 , wherein the at least one enteric polymer is HPMCAS.
10. The oral pharmaceutical composition of claim 1 , wherein the at least one sustained release polymer is selected from the group consisting of ethyl cellulose, trimethylammoniumethyl methacrylate chloride, 30% by weight dispersion of poly(ethylacrylat-methylmethacrylat), hydroxypropyl methylcellulose (HPMC), hydroxyethyl cellulose (HEC), polyvinylpyrrolidone (PVP), and combinations thereof.
11. The oral pharmaceutical composition of claim 10 , wherein the at least one sustained release polymer is ethyl cellulose.
12. The oral pharmaceutical composition of claim 2 , wherein the first and second pharmaceutically active ingredients in combination are present in the composition in the amount of about 25% w/w.
13. The oral pharmaceutical composition of claim 2 , wherein the first and second pharmaceutically active ingredients are amphetamine salts or the first and second pharmaceutically active ingredients are opiate drugs.
14. The oral pharmaceutical composition of claim 13 , wherein the first and second pharmaceutically active ingredients are a mixture of amphetamine salts.
15. The oral pharmaceutical composition of claim 14 , wherein the mixture of amphetamine salts is a mixture of neutral salts of dextroamphetamine sulfate, amphetamine sulfate, the dextro isomer of amphetamine saccharate, and d, l-amphetamine aspartate.
16. The oral pharmaceutical composition of claim 1 , wherein about 50% by weight of the total amount of the first and second pharmaceutically active ingredients is present in the polymer matrix and about 50% by weight of the total amount of the first and second pharmaceutically active ingredients is present in the population of discrete particles adhering to the outer surface of the polymer matrix.
17. The oral pharmaceutical composition of claim 16 , wherein the first and second pharmaceutically active ingredients are the same.
18. The oral pharmaceutical composition of claim 17 , wherein the first and second pharmaceutically active ingredients are a mixture of amphetamine salts.
19. The oral pharmaceutical composition of claim 18 , wherein the mixture of amphetamine salts includes a mixture of neutral salts of dextroamphetamine sulfate, amphetamine sulfate, the dextro isomer of amphetamine saccharate, and d, l-amphetamine aspartate.
20. The oral pharmaceutical composition of claim 2 , wherein the optional plasticizer and the optional binder are present in the polymer matrix.
21. The oral pharmaceutical composition of claim 20 , wherein the plasticizer is selected from the group consisting of acetyltriethyl citrate, triethyl citrate, acetyltributyl citrate; dibutylsebacate, triacetin, polyethylene glycols, propylene glycol, and combinations thereof.
22. The oral pharmaceutical composition of claim 21 , wherein the plasticizer is triethyl citrate.
23. The oral pharmaceutical composition of claim 20 , wherein the binder is selected from the group consisting of citric acid, acacia, alginic acid, carboxymethylcellulose sodium, microcrystalline cellulose, dextrin, ethylcellulose, gelatine, glucose, guar gum, hydroxypropyl methylcellulose, methylcellulose, polyethylene oxide, povidone, pregelatinised starch, syrup, polyvinylpyrrolidone, polyvinylpyrrolidone/vinyl acetate copolymer, and combinations thereof.
24. The oral pharmaceutical composition of claim 23 , wherein the binder is methylcellulose.
25. The oral pharmaceutical composition of claim 1 , wherein the outer surface of the polymer matrix is treated with a granulating solvent prior to depositing the second pharmaceutically active ingredient as the population of discrete particles thereon.
26. The oral pharmaceutical composition of claim 25 , wherein the granulating solvent is a hydroalcoholic solvent.
27. The oral pharmaceutical composition of claim 16 , wherein the hydroalcoholic solvent contains about 80% ethanol and about 20% water.