Opioid abuse deterrent dosage forms
Described herein are oral abuse deterrent pharmaceutical compositions, methods for making the same, and methods for treating pain by administering the pharmaceutical composition to a subject in need thereof. In particular, an oral abuse deterrent pharmaceutical composition comprising a soft capsule and a controlled release matrix comprising oxycodone are described.
1. A method for treating, reducing the symptoms of, or retarding the onset of pain comprising administering to a subject in need thereof of an oral pharmaceutical composition comprising about 35% to about 70% by mass glyceryl monolinoleate, about 20% to about 50% by mass polyethylene oxide having a molecular weight (M v ) of about 1,000,000 to about 7,000,000, and oxycodone or a salt thereof.
2. The method of claim 1 , wherein the pharmaceutical composition comprises:
(a) about 50% to about 70% by mass glyceryl monolinoleate;
(b) about 25% to about 40% by mass polyethylene oxide having a molecular weight (M v ) of about 1,000,000 to about 7,000,000; and
(c) about 1% to about 20% by mass of oxycodone or a salt thereof.
3. The method of claim 1 , wherein the pain arises from one or more of diabetic neuropathy, chronic arthritis, osteoarthritis, rheumatoid arthritis, acute tendonitis, bursitis, headaches, migraines, chronic neuropathies, shingles, premenstrual symptoms, sports injuries, malignancy, radiculopathy, sciatica/sciatic pain, sarcoidosis, necrobiosis, lipoidica, granuloma annulare, trauma, cancer, or a combination thereof.
4. The method of claim 1 , wherein upon ingestion by the subject the composition is capable of achieving one or more of the following pharmacokinetic parameters:
(a) a mean plasma oxycodone T max of about 1 hours to about 8 hours;
(b) a mean plasma oxycodone C max of about 10 ng/mL to about 150 ng/mL; or
(c) a mean plasma oxycodone AUC 0→∞ of about 100 h·ng/mL to about 1000 h·ng/mL.
5. The method of claim 1 , wherein the pharmaceutical composition forms an abuse deterrent elastic semi-solid composition after having been heated at a temperature of about 50° C. to about 80° C. for about 10 min to about 180 min, and cooled to room temperature.
6. The method of claim 1 , wherein the pharmaceutical composition comprises a mass ratio of polyethylene oxide to glyceryl monolinoleate of about 1:2.
7. The method of claim 1 , wherein the pharmaceutical composition comprises a mass ratio range of oxycodone to polyethylene oxide of about 1:1 to about 1:20.
8. The method of claim 1 , wherein the oxycodone comprises about 0.5% to about 20% of the composition by mass.
9. The method of claim 1 , wherein the composition further comprises one or more antioxidants.
10. The method of claim 9 , wherein the antioxidant comprises about 0.05% to about 0.5% of the composition by mass.
11. The method of claim 1 , wherein the polyethylene oxide comprises a polyethylene oxide having an average molecular weight (M v ) of about 4,000,000.
12. The method of claim 1 , wherein the oxycodone comprises about 5 mg, about 10 mg, about 15 mg, about 20 mg, about 30 mg, or about 40 mg of oxycodone hydrochloride.
13. The method of claim 1 , wherein the composition is encapsulated in a capsule.
14. A method for delivering about 40 mg of oxycodone comprising administering to a subject one or more pharmaceutical dosage forms comprising about 35% to about 70% by mass glyceryl monolinoleate, about 20% to about 50% by mass polyethylene oxide having a molecular weight (M v ) of about 1,000,000 to about 7,000,000, and oxycodone or a salt thereof, the method capable of achieving one or more of the following pharmacokinetic parameters following ingestion by the subject:
(a) a mean plasma oxycodone T max of about 4.5 hours to about 5.0 hours;
(b) a mean plasma oxycodone C max of about 40 ng/mL to about 65 ng/mL;
(c) a mean plasma oxycodone AUC 0→τ of about 400 h·ng/mL to about 500 h·ng/mL;
(d) a mean plasma oxycodone AUC 0→∞ of about 400·h·ng/mL to about 500 h·ng/mL;
(e) a mean oxycodone half-life (t 1/2 ) of about 4.4 hours to about 4.6 hours; or
(f) a mean oxycodone overall elimination rate constant (λ z ) of about 0.14 h −1 to about 0.17 h −1 .
15. The method of claim 14 , wherein the pharmaceutical dosage form exhibits an in vitro dissolution rate at pH 1.2 of about 50% after about 90 minutes.
16. The method of claim 14 , wherein the dosage form comprises a capsule encapsulating an abuse deterrent elastic semi-solid composition comprising:
(a) about 35% to about 70% by mass glyceryl monolinoleate;
(b) about 20% to about 50% by mass polyethylene oxide having a molecular weight (M v ) of about 1,000,000 to about 7,000,000; and
(c) about 1% to about 20% by mass of oxycodone or a salt thereof; and
the dosage form having been heated to about 50° C. to about 80° C. for about 10 min to about 180 min, and cooled to room temperature.
17. A method for inhibiting extraction of oxycodone from a pharmaceutical composition, the method comprising: administering a dosage form comprising a capsule encapsulating a:
(a) about 35% to about 70% by mass glyceryl monolinoleate;
(b) about 20% to about 50% by mass polyethylene oxide comprising having a molecular weight (M v ) of about 1,000,000 to about 7,000,000; and
(c) about 1% to about 20% by mass of oxycodone or a salt thereof; and
the dosage form having been heated to about 50° C. to about 80° C. for about 10 min to about 180 min, and cooled to room temperature; and
wherein the dosage form is resistant to crushing, grating, grinding, cutting, solvation, or dissolution in water or alcohol.
18. The method of claim 17 , wherein the capsule comprises a coated soft capsule.