Sustained release formulations of opioid and nonopioid analgesics
View Patent ↗The present invention relates to SRSR solid dosage forms for administering pharmaceutical agents, particularly Hydrocodone and acetaminophen, methods for preparing the dosage forms, and methods for providing therapeutic agents to patients in need of treatment.
1. A pharmaceutical composition comprising at least two sustained release subunits:
a first sustained release subunit that comprises acetaminophen and hydrocodone or an equivalent amount of another acceptable salt or free base of hydrocodone thereof;
a second sustained release subunit that comprises acetaminophen and hydrocodone or an equivalent amount of another acceptable salt or free base of hydrocodone thereof;
wherein each of the sustained release subunits are in a monoeximic dosage form selected from the group consisting of an osmotic system and a matrix system,
wherein each monoexemic osmotic system contains only one membrane to control the rate of drug release, and
wherein the sustained release subunits release the drugs contained therein over a period of longer than two hours.
2. The pharmaceutical composition of claim 1 , wherein the composition contains acetaminophen between about 20 and about 100 times by weight of hydrocodone bitartrate or an equivalent amount of another acceptable salt or free base of hydrocodone thereof.
3. The pharmaceutical composition of claim 1 , wherein the first subunit and the second subunit each contain a single rate controlling mechanism.
4. The pharmaceutical composition of claim 3 , wherein the single rate controlling mechanism comprises at least one pharmaceutically acceptable hydrophobic rate controlling material, a pharmaceutically acceptable hydrophilic rate controlling material, a non-polymer rate controlling material or any combinations thereof.
5. The pharmaceutical composition of claim 1 , wherein the first and second subunit each comprise a monoeximic dosage form.
6. The pharmaceutical composition of claim 5 , wherein the first and second subunits comprise the same type of monoeximic dosage forms or different types of monoeximic dosage forms.
7. The pharmaceutical composition of claim 6 , wherein each of the monoeximic dosage forms comprises a matrix system.
8. The pharmaceutical composition of claim 6 , wherein each of the monoeximic dosage forms comprises an osmotic system.
9. The pharmaceutical composition of claim 6 , wherein one of the monoeximic dosage forms comprises a matrix system and the other monoeximic dosage forms comprises an osmotic system.
10. The pharmaceutical composition of claim 1 , wherein the composition is capable of reducing pain intensity in a patient within about 1 hour.
11. The pharmaceutical composition of claim 10 , wherein the composition releases at least 90% of the hydrocodone and acetaminophen in vitro within 12 hours.
12. The pharmaceutical composition of claim 10 , wherein the composition releases at least 90% of the hydrocodone and acetaminophen in vitro within about 8 hours.
13. The pharmaceutical composition of claim 1 , wherein the dosage form is adapted to release about 19% to 49% of the hydrocodone and acetaminophen in vitro within 0.75 hours.
14. The pharmaceutical composition of claim 13 , wherein the dosage form releases at least 90% of the hydrocodone and acetaminophen within 12 hours.
15. The pharmaceutical composition of claim 13 , wherein the dosage releases at least 90% of the hydrocodone and acetaminophen within about 8 hours.
16. The pharmaceutical composition of claim 1 , wherein the dosage form comprises about 500 mg of acetaminophen and about 15 mg of hydrocodone bitartrate.
17. The pharmaceutical composition of claim 1 , wherein the human in which the AUC and Cmax for both hydrocodone and acetaminophen is measured is a non-poor CYP2D6 metabolizer, and
wherein the dosage form produces a Cmax for hydromorphone in the human of between about 0.12 ng/ml and about 0.35 ng/ml after a single dose of 30 mg of hydrocodone bitartrate.
18. The pharmaceutical composition of claim 1 , wherein the plasma concentration for hydrocodone 12 hours after a single 30 mg dose of hydrocodone bitartrate is between about 11.0 ng/ml and about 27.4 ng/ml.
19. The pharmaceutical composition of claim 1 , wherein when a single 1000 mg dose of acetaminophen is administered to the human, the plasma concentration for acetaminophen 12 hours after administration is between about 0.7 μg/ml and about 2.5 μg/ml.
20. The pharmaceutical composition of claim 1 , wherein when a single 1000 mg dose of acetaminophen is administered to the human, the plasma concentration for acetaminophen 12 hours after administration is between about 0.7 μg/ml and about 2.5 μg/ml.
21. The pharmaceutical composition of claim 1 , wherein after a single dose of 30 mg of hydrocodone bitartrate, the plasma concentration profile exhibits a width at half height for hydrocodone of between about 6.4 hours and about 19.6 hours.
22. The pharmaceutical composition of claim 1 , wherein after a single dose of 30 mg of hydrocodone bitartrate, the plasma concentration profile exhibits a width at half height for hydrocodone of between about 8.4 hours and about 19.6 hours.
23. The sustained pharmaceutical composition of claim 1 , wherein after a single does of 1000 mg of acetaminophen, the plasma concentration profile exhibits a width at half height for acetaminophen of between about 0.8 hours and about 12.3 hours.