Pulsed extended-pulsed and extended-pulsed pulsed drug delivery systems
The disclosure is directed to drug delivery devices that provide for combinations of extended and pulsed controlled release delivery of active pharmaceutical ingredient(s) APIs. The described drug delivery devices for oral administration of therapeutic compositions can include two or more populations of unit dosage forms including one or more API's in various combinations of pulsed and delayed/extended delivery formulations. The population of unit dosage forms are provided in a variety of different vehicles such as granules, beads, pellets, or tablets and can be contained within a drug delivery device of the present disclosure.
1. A drug delivery device for oral administration of an active pharmaceutical ingredient (API), the device comprising:
a) a first population of unit dosage forms comprising a core, wherein the core comprises the API and a super-disintegrant and wherein the first population of unit dosage forms is not coated;
b) a second population of unit dosage forms comprising a core, wherein the core comprises the API and at least one of hydroxypropyl methyl cellulose and polyethylene oxide and wherein the second population of unit dosage forms comprises a pH-reactive coat; and
c) a third population of unit dosage forms comprising a core, wherein the core comprises the API and a super-disintegrant and wherein the third population of unit dosage forms comprises a pH-reactive coat, wherein the API is d-threo-methylphenidate hydrochloride and is present in the first population in an amount of 32%, in the second population in an amount of 32% and in the third population in an amount of 16%.
2. The drug delivery device of claim 1 , wherein the hydroxypropyl methyl cellulose is present in an amount of 12%.
3. The drug delivery device of claim 1 , wherein the super-disintegrant is sodium starch glycolate.
4. The drug delivery device of claim 3 , wherein the super-disintegrant is present in the first population in an amount of 1% and in the third population in an amount of 1%.
5. The drug delivery device of claim 1 , wherein each of the first, second, and third populations further comprises lactose, silicone dioxide, microcrystalline cellulose, and magnesium stearate.
6. The drug delivery device of claim 5 , wherein the silicone dioxide is present in each of the first, second, and third populations in an amount of 1%.
7. The drug delivery device of claim 5 , wherein the magnesium stearate is present in each of the first, second, and third populations in an amount of 1%.
8. The drug delivery device of claim 5 , wherein the microcrystalline cellulose is present in the first and third populations in an amount of 20% and in the second population in an amount of 14%.
9. The drug delivery device of claim 1 , wherein the second population is coated to a coverage of 4 mg per cm2.
10. The drug delivery device of claim 1 , wherein the third population is coated to a coverage of 6 mg per cm 2 .
11. The drug delivery device of claim 1 , comprising one member from each of the first, second, and third populations assembled within a holding chamber/reservoir made of hard gelatin or hydroxypropyl methyl cellulose.
12. The drug delivery device of claim 1 , wherein the core of the second population of unit dosage forms comprises hydroxypropyl methyl cellulose.
13. A drug delivery device for oral administration of an active pharmaceutical ingredient (API), the device comprising:
a) a first population of unit dosage forms comprising a core, wherein the core comprises the API and at least one of hydroxypropyl methyl cellulose and polyethylene oxide and wherein the first population of unit dosage forms comprises an immediate release coating comprising the API;
b) a second population of unit dosage forms comprising a core, wherein the core comprises the API and a super-disintegrant and wherein the second population of unit dosage forms comprises a pH-reactive coat, wherein the API is risperidone and is present in the first population in an amount of 3% and in the second population in an amount of 2%.
14. The drug delivery device of claim 13 , wherein 1 mg of the API is blended with the immediate release coating and applied to the first population of unit dosage forms to apply a weight gain of 3%.
15. The drug delivery device of claim 13 , wherein the hydroxypropyl methyl cellulose is present in an amount of 12%.
16. The drug delivery device of claim 13 , wherein the super-disintegrant is cross-linked N-vinyl-2-pyrrolidone.
17. The drug delivery device of claim 16 , wherein the super-disintegrant is present in the second population in an amount of 2%.
18. The drug delivery device of claim 13 , wherein each of the first and second populations further comprises lactose, sodium lauryl sulphate, silicone dioxide, microcrystalline cellulose, and magnesium stearate.
19. The drug delivery device of claim 18 , wherein the silicone dioxide is present in each of the first and second populations in an amount of 1%.
20. The drug delivery device of claim 18 , wherein the magnesium stearate is present in each of the first and second populations in an amount of 1%.
21. The drug delivery device of claim 18 , wherein the microcrystalline cellulose is present in each of the first and second populations in an amount of 20%.
22. The drug delivery device of claim 18 , wherein the sodium lauryl sulphate is present in each of the first and second populations in an amount of 5%.
23. The drug delivery device of claim 13 , wherein the second population is coated to a coverage of 4 mg per cm 2 .
24. The drug delivery device of claim 13 , comprising one member from each of the first and second populations assembled within a holding chamber/reservoir made of hard gelatin or hydroxypropyl methyl cellulose.
25. The drug delivery device of claim 13 , wherein the core of the first population of unit dosage forms comprises hydroxypropyl methyl cellulose.
26. A drug delivery device for oral administration of an active pharmaceutical ingredient (API), the device comprising:
a) a first population of unit dosage forms comprising a core, wherein the core comprises the API and at least one of hydroxypropyl methyl cellulose and polyethylene oxide and wherein the first population of unit dosage forms comprises a pH-reactive coat;
b) a second population of unit dosage forms comprising a core, wherein the core comprises the API, a super-disintegrant, an acid, and a base and wherein the second population of unit dosage forms is not coated, wherein the API is duloxetine and is present in the first population in an amount of 20% and in the second population in an amount of 10%.
27. The drug delivery device of claim 26 , wherein the hydroxypropyl methyl cellulose is present in an amount of 15%.
28. The drug delivery device of claim 26 , wherein the super-disintegrant is cross-linked N-vinyl-2-pyrrolidone.
29. The drug delivery device of claim 28 , wherein the super-disintegrant is present in an amount of 2%.
30. The drug delivery device of claim 26 , wherein the acid comprises citric acid and tartaric acid.
31. The drug delivery device of claim 30 , wherein the citric acid is present in an amount of 2% and the tartaric acid is present in an amount of 4%.
32. The drug delivery device of claim 26 , wherein the base is sodium bicarbonate.
33. The drug delivery device of claim 32 , wherein the base is present in an amount of 6.8%.
34. The drug delivery device of claim 26 , wherein each of the first and second populations further comprises lactose, sodium lauryl sulphate, silicone dioxide, microcrystalline cellulose, and magnesium stearate.
35. The drug delivery device of claim 34 , wherein the silicone dioxide is present in each of the first and second populations in an amount of 1%.
36. The drug delivery device of claim 34 , wherein the magnesium stearate is present in each of the first and second populations in an amount of 1%.
37. The drug delivery device of claim 34 , wherein the microcrystalline cellulose is present in each of the first and second populations in an amount of 20%.
38. The drug delivery device of claim 34 , wherein the sodium lauryl sulphate is present in each of the first and second populations in an amount of 5%.
39. The drug delivery device of claim 26 , wherein the first population is coated to a coverage of 4 mg per cm 2 .
40. The drug delivery device of claim 26 , comprising one member from each of the first and second populations assembled within a holding chamber/reservoir made of hard gelatin or hydroxypropyl methyl cellulose.
41. The drug delivery device of claim 26 , wherein the core of the first population of unit dosage forms comprises hydroxypropyl methyl cellulose.