Cellulosic gel material as a pharmaceutical excipient
A method of making a pharmaceutical tablet comprises (a) combining (i) an aqueous networked cellulose gel with (ii) filler and (iii) an active agent to form a mixture thereof; (b) casting the mixture to form a wet tablet; (c) drying the wet tablet to form a dry pharmaceutical tablet; and then (d) optionally coating the tablet (e.g., with an enteric coating). Pharmaceutical tablets produced by such methods are also described.
1. A method of making a pharmaceutical tablet, comprising:
(a) producing an aqueous networked cellulose gel by: (i) hydrolyzing cellulose in an acidic dissolution media at a temperature of 5 to 40° C. for 10 to 60 minutes to form a first mixture; (ii) precipitating said hydrolyzed cellulose by combining said first mixture with an antisolvent, and then, in any order; (iii) separating said cellulose precipitate from said antisolvent and acidic dissolution media; (iv) adjusting or neutralizing the pH of said cellulose precipitate to a pH of from 4 to 9; and (v) washing said cellulose precipitate with water to form said aqueous networked cellulose gel;
(b) combining (i) said aqueous networked cellulose gel with (ii) water insoluble particulate filler and (iii) a water soluble active agent to form a mixture thereof;
(c) casting said mixture to form a wet tablet;
(d) drying said wet tablet to form a dry pharmaceutical tablet; and then
(e) optionally coating said tablet.
2. The method of claim 1 , wherein said water insoluble filler comprises microcrystalline cellulose.
3. The method of claim 1 , wherein said dry pharmaceutical tablet does not fracture under a force of 50 Newtons as applied by a tablet press.
4. The method of claim 1 , wherein said pharmaceutical tablet shrinks less than 40 percent in diameter during said drying step.
5. The method of claim 1 , wherein said casting step is carried out at atmospheric pressure.
6. The method of claim 1 , wherein said drying step is carried out by air drying at room temperature, by heating, by vacuum drying, or a combination thereof.
7. The method of claim 1 , wherein said active agent is selected from the group consisting of paracetamol, aspirin, ibuprofen, naproxen, Atorvastatin, Clopidogrel, Esomeprazole, Amlodipine, Olanzapine, Valsartan, Risperidone, Venlafaxine, Pantoprazole, Montelukast, Quetiapine, Rosiglitazone, Pioglitazone, Simvastatin, Escitalopram, Donepezil, Irbesartan, Rosuvastatin, Aripiprazole, Candesartan, Sildenafil, Levofloxacin, Duloxetine, Methylphenidate, and pharmaceutically acceptable salts thereof.
8. The method of claim 1 , said dry pharmaceutical tablet comprising:
(a) from 2 to 80 percent by weight of networked cellulose;
(b) from 10 to 95 percent by weight of filler;
(c) from 0.1 to 20 percent by weight of an active agent; and
(d) optionally, from 0.05 to 10 percent by weight of an enteric coating.
9. A pharmaceutical tablet produced by the process of claim 1 .
10. The pharmaceutical table of claim 9 , comprising:
(a) from 2 to 80 percent by weight of networked cellulose;
(b) from 10 to 95 percent by weight of filler;
(c) from 0.1 to 20 percent by weight of an active agent; and
(d) optionally, from 0.05 to 10 percent by weight of a coating.
11. The tablet of claim 10 , wherein said water insoluble filler comprises microcrystalline cellulose.
12. The tablet of claim 10 , wherein said dry pharmaceutical tablet does not fracture under a force of 50 Newtons.
13. The tablet of claim 10 , wherein said tablet does not fracture under a force of 150 Newtons.
14. The tablet of claim 10 , wherein said active agent is selected from the group consisting of paracetamol, aspirin, ibuprofen, naproxen, Atorvastatin, Clopidogrel, Esomeprazole, Amlodipine, Olanzapine, Valsartan, Risperidone, Venlafaxine, Pantoprazole, Montelukast, Quetiapine, Rosiglitazone, Pioglitazone, Simvastatin, Escitalopram, Donepezil, Irbesartan, Rosuvastatin, Aripiprazole, Candesartan, Sildenafil, Levofloxacin, Duloxetine, Methylphenidate, and pharmaceutically acceptable salts thereof.
15. The tablet of claim 10 , wherein said active agent is included in an amount of from 0.01 to 4000 milligrams per tablet.
16. A pharmaceutical tablet of claim 10 consisting essentially of:
(a) from 2 to 80 percent by weight of networked cellulose;
(b) from 10 to 95 percent by weight of filler;
(c) from 0.1 to 20 percent by weight of an active agent selected from the group consisting of paracetamol, aspirin, ibuprofen, naproxen, Atorvastatin, Clopidogrel, Esomeprazole, Amlodipine, Olanzapine, Valsartan, Risperidone, Venlafaxine, Pantoprazole, Montelukast, Quetiapine, Rosiglitazone, Pioglitazone, Simvastatin, Escitalopram, Donepezil, Irbesartan, Rosuvastatin, Aripiprazole, Candesartan, Sildenafil, Levofloxacin, Duloxetine, Methylphenidate, and pharmaceutically acceptable salts thereof; and
(d) optionally, from 0.05 to 10 percent by weight of a coating;
wherein said tablet does not fracture under a force of 50 Newtons.
17. The tablet of claim 16 , wherein said water insoluble filler comprises microcrystalline cellulose.
18. The method of claim 1 , wherein:
said dry pharmaceutical tablet does not fracture under a force of 50 Newtons as applied by a tablet press; and
said pharmaceutical tablet shrinks less than 40 percent in diameter during said drying step.
19. The method of claim 1 , wherein said antisolvent is ethanol or water.
20. The method of claim 1 , wherein:
said dry pharmaceutical tablet does not fracture under a force of 50 Newtons as applied by a tablet press;
said pharmaceutical tablet shrinks less than 40 percent in diameter during said drying step;
said casting step is carried out at atmospheric pressure;
said drying step is carried out by air drying at room temperature, by heating, by vacuum drying, or a combination thereof;
said active agent is selected from the group consisting of paracetamol, aspirin, ibuprofen, naproxen, Atorvastatin, Clopidogrel, Esomeprazole, Amlodipine, Olanzapine, Valsartan, Risperidone, Venlafaxine, Pantoprazole, Montelukast, Quetiapine, Rosiglitazone, Pioglitazone, Simvastatin, Escitalopram, Donepezil, Irbesartan, Rosuvastatin, Aripiprazole, Candesartan, Sildenafil, Levofloxacin, Duloxetine, Methylphenidate, and pharmaceutically acceptable salts thereof;
said dry pharmaceutical tablet comprising: (a) from 2 to 80 percent by weight of networked cellulose; (b) from 10 to 95 percent by weight of filler; (c) from 0.1 to 20 percent by weight of an active agent; and (d) optionally, from 0.05 to 10 percent by weight of an enteric coating.
21. The method of claim 20 , wherein said active agent is paracetamol.
22. A pharmaceutical tablet of claim 16 , wherein said active agent is paracetamol.