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Last Updated: August 11, 2022

Claims for Patent: 9,775,808


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Summary for Patent: 9,775,808
Title:Tamper resistant dosage forms
Abstract: The present invention relates to pharmaceutical dosage forms, for example to a tamper resistant dosage form including an opioid analgesic, and processes of manufacture, uses, and methods of treatment thereof.
Inventor(s): McKenna; William H. (Yonkers, NY), Mannion; Richard O. (Furlong, PA), O'Donnell; Edward P. (Basking Ridge, NJ), Huang; Haiyong H. (Princeton, NJ)
Assignee: PURDUE PHARMA L.P. (Stamford, CT) PURDUE PHARMACEUTICALS L.P. (Wilson, NC)
Application Number:15/413,635
Patent Litigation and PTAB cases: See patent lawsuits and PTAB cases for patent 9,775,808
Patent Claims: 1. A pharmaceutical composition comprising: at least one active agent comprising oxycodone or a pharmaceutically acceptable salt thereof; at least one high molecular weight polyethylene oxide (PEO), having an approximate molecular weight of from 1 million to 15 million; at least one of an additive and a film coating; and optionally at least one low molecular weight PEO having an approximate molecular weight of less than 1,000,000; wherein (a) the active agent and high molecular weight PEO are combined in a solid oral extended release dosage form that is (i) compression shaped, (ii) air cured by heated air, without compression, for at least about 5 minutes at a temperature above the softening temperature of the high molecular weight PEO, (iii) cooled, and (iv) hardened; (b) the high molecular weight PEO comprises at least about 30% (by weight) of the dosage form; (c) the molecular weight of each PEO is based on rheological measurements; and (d) the total weight of the dosage form is calculated by excluding the combined weight of said film coatings.

2. A pharmaceutical composition according to claim 1, wherein the high molecular weight PEO is at least partially melted upon curing.

3. A pharmaceutical composition according to claim 1, wherein the curing temperature is from about 70.degree. C. to about 85.degree. C. and the curing time is from about 10 minutes to about 10 hours.

4. A pharmaceutical composition according to claim 1, wherein the curing temperature is at least about 60.degree. C. and the curing time is at least about 10 minutes.

5. A pharmaceutical composition according to claim 4, wherein the curing temperature does not exceed about 90.degree. C. and the curing time does not exceed about 24 hours.

6. A pharmaceutical composition according to claim 5, wherein the curing time does not exceed about 10 hours.

7. A pharmaceutical composition according to claim 5, wherein the active agent is present in a dosage amount selected from 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, and 80 mg.

8. A pharmaceutical composition according to claim 7, wherein the dosage form is expanded upon curing, as measured by a decrease in density of at least about 1%, and the dosage form provides a hardness of at least about 439 N.

9. A pharmaceutical composition according to claim 8, wherein the low molecular weight PEO is present, has an approximate molecular weight of from 100,000 to 900,000, and comprises at least about 10% (by weight) of the dosage form.

10. A pharmaceutical composition according to claim 8, wherein the dosage form is a tablet, at least one film coating is present; at least one additive is present; and the additive is selected from at least one of an anti-tacking agent, an antioxidant, an immediate release component, and a retardant.

11. A pharmaceutical composition comprising: at least one active agent comprising oxycodone hydrochloride; at least one high molecular weight polyethylene oxide (PEO) having an approximate molecular weight of from 1 million to 8 million; at least one additive comprising an anti-tacking agent, an antioxidant, an immediate release component, or a retardant; optionally a film coating; and optionally at least one low molecular weight PEO having an approximate molecular weight of less than 1,000,000; wherein (a) the active agent and high molecular weight PEO are combined in a solid oral extended release dosage form that is (i) compression shaped, (ii) air cured by heated air, without compression, for a curing time of at least about 10 minutes at a curing temperature of at least about 60.degree. C., (iii) cooled, and (iv) hardened; (b) the high molecular weight PEO comprises at least about 50% (by weight) of the dosage form; (c) the active agent comprises at least about 5% (by weight) of the dosage form; (d) the molecular weight of each PEO is based on rheological measurements; and (e) the total weight of the dosage form is calculated by excluding the combined weight of said film coatings.

12. A pharmaceutical composition according to claim 11, wherein the dosage form is a tablet; at least one additive comprises an anti-tacking agent; the compression shaped tablet is cured and cooled in a convection curing device provided with inlet air, exhaust air, and a bed of free flowing tablets; the tablet is cured by air having a curing temperature of about 60.degree. C. to about 90.degree. C., for a curing time of about 10 minutes to about 10 hours, and is cooled by air having a cooling temperature below about 50.degree. C.; and each of the curing temperature and the cooling temperature is one of (a) the temperature of the inlet air, or (b) the temperature of the exhaust air.

13. A pharmaceutical composition according to claim 12, wherein the high molecular weight PEO comprises at least about 65% (by weight) of the tablet; and the active agent is present in a twice-daily dosage amount selected from 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, and 80 mg.

14. A pharmaceutical composition according to claim 13, wherein the high molecular weight PEO has an approximate molecular weight selected from 4 million and 7 million.

15. A pharmaceutical composition according to claim 13, wherein the curing temperature is from about 70.degree. C. to about 85.degree. C.

16. A pharmaceutical composition according to claim 13, wherein the tablet is expanded upon curing, as measured by a decrease in tablet density of at least about 2%, and has a hardness of at least about 439 N.

17. A pharmaceutical composition according to claim 16, wherein the curing temperature is from about 70.degree. C. to about 85.degree. C.

18. A pharmaceutical composition according to claim 16, wherein the high molecular weight PEO comprises at least about 79% (by weight) of the dosage form.

19. A pharmaceutical composition according to claim 16, wherein the high molecular weight PEO comprises at least about 85% (by weight) of the dosage form.

20. A pharmaceutical composition according to claim 16, wherein at least one of the additive and the film coating comprises at least one of butylated hydroxytoluene (BHT), magnesium stearate, talc, silica, fumed silica, colloidal silica dioxide, calcium stearate, carnauba wax, stearic acid, stearyl alcohol, mineral oil, paraffin, micro crystalline cellulose, glycerin, propylene glycol, polyethylene glycol, lactose, povidone, triacetin, and hydroxypropyl cellulose.

21. A pharmaceutical composition according to claim 16, wherein the low molecular weight PEO is present, has an approximate molecular weight of from 100,000 to 900,000, and comprises at least about 10% (by weight) of the dosage form.

22. A pharmaceutical composition according to claim 16, wherein the convection curing device is a coating pan and the curing temperature and cooling temperature are each the exhaust temperature of the coating pan.

23. A pharmaceutical composition according to claim 22, wherein the curing temperature has a plateau-like temperature profile.

24. A pharmaceutical composition according to claim 22, wherein the cooling temperature is from about 30.degree. C. to about 34.degree. C.

25. A pharmaceutical composition according to claim 16, wherein the high molecular weight PEO has an approximate molecular weight selected from 4 million and 7 million.

26. A pharmaceutical composition according to claim 25, wherein at least one of the additive and the film coating comprises at least one of butylated hydroxytoluene (BHT), magnesium stearate, talc, silica, fumed silica, colloidal silica dioxide, calcium stearate, carnauba wax, stearic acid, stearyl alcohol, mineral oil, paraffin, micro crystalline cellulose, glycerin, propylene glycol, polyethylene glycol, lactose, povidone, triacetin, and hydroxypropyl cellulose.

27. A pharmaceutical composition according to claim 16, wherein the tablet, when subjected to about 15,000 pounds of applied pressure from a hydraulic press, provides a flattened tablet that is flattened without breaking apart; has a thickness that is no more than about 60% of the thickness of the non-flattened tablet; and provides a dissolution of active agent, with ethanol, that deviates no more than about 20% points from the dissolution of a non-flattened reference tablet, without ethanol; wherein dissolution is measured (i) as a percent amount of active agent released at selected time points up to and including at least a 2 hour period; (ii) using a USP Apparatus 1 (basket) at 37.degree. C. and 100 rpm, in 900 ml simulated gastric fluid without enzymes (SGF) for the non-flattened tablet, and further comprising 40% ethanol for the flattened tablet.

28. A pharmaceutical composition according to claim 27, wherein the deviation in dissolution upon flattening is no more than about 15% points.

29. A pharmaceutical composition according to claim 16, wherein the tablet, when measured (a) without an antioxidant additive and (b) as the average of at least 10 of 100 tablet samples stored at 40.degree. C. and 75% relative humidity for at least 3 months; provides a dissolution of the active agent that deviates no more than about 10% points from the dissolution of a reference tablet before storage; wherein dissolution is measured (i) as a percent amount of active agent released at selected time points up to and including at least a 12 hour period; (ii) using a USP Apparatus 1 (basket) at 37.degree. C. and 100 rpm, in 900 ml simulated gastric fluid without enzymes (SGF).

30. A pharmaceutical composition according to claim 29, wherein the deviation in dissolution upon storage is no more than 5% points.

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Serving leading biopharmaceutical companies globally:

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