Abuse-deterrent opioids
Described herein are abuse deterrent controlled release oral pharmaceutical compositions comprising and methods for making the same. In particular, an abuse deterrent controlled release oral pharmaceutical composition comprising a soft capsule and an abuse deterrent controlled release matrix comprising an active pharmaceutical ingredient are described.
1. An abuse deterrent oral pharmaceutical composition comprising a soft gelatin capsule shell encapsulating a tamper resistant, homogenous viscous, yet flowable matrix consisting essentially of:
(a) about 50% to about 70% by mass olive oil, soybean oil, or a combination thereof;
(b) about 3% to about 10% by mass ethylcellulose;
(d) about 2% to about 30% by mass hydroxypropyl methylcellulose;
(e) about 4% to about 11% by mass polyethylene glycol having a molecular weight of about 200 to about 8000;
(f) about 1% to about 35% by mass of one or more active pharmaceutical ingredients that is dissolved in the flowable matrix; and
(g) optionally one or more antioxidants.
2. The composition of claim 1 , wherein the anti-oxidant comprises about 0.05% to about 0.5% by mass.
3. The composition of claim 1 , wherein the composition comprises a mass ratio of active pharmaceutical ingredient to the combined mass of the other components of about 1:100 to about 1:3.
4. The composition of claim 1 , wherein the ethylcellulose is capable of forming a gel at a temperature of about 90° C. to about 120° C.
5. The composition of claim 1 , wherein the ethylcellulose comprises a viscosity value of about 3 cP to about 20 cP.
6. The composition of claim 1 , wherein the hydroxypropylmethylcellulose has a viscosity value of about 50 cP to about 100,000 cP.
7. The composition of claim 1 , wherein the anti-oxidant comprises butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), or a combination thereof.
8. The composition of claim 1 , wherein the active pharmaceutical ingredient comprises at least one of: hydrocodone, morphine, morphine analogues, or morphine antagonists, tapentadol, codeine, morphine, methadone, fentanyl and analogs, hydrocodone hydrochloride, hydrocodone bitartrate, hydromorphone, oxymorphone, oxycodone, meperidine, propoxyphene, flunitrazepam, barbiturates, amytal, nembutal, seconal, phenobarbital; benzodiazepines, zolpidem, zaleplon, eszopiclone, amphetamines, methylphenidate, or a combination thereof.
9. The composition of claim 1 , wherein the active pharmaceutical ingredient comprises hydrocodone or oxycodone.
10. The composition of claim 1 , wherein the tamper resistant, homogenous viscous, yet flowable matrix consists essentially of:
(a) about 50% to about 70% by mass soybean oil;
(b) about 2% to about 7% by mass ethylcellulose;
(c) about 2% to about 15% by mass hydroxypropylmethylcellulose;
(d) about 4% to about 11% by mass polyethylene glycol 400; and
(e) about 10.5% by mass of hydrocodone or oxycodone; and optionally
(f) about 0.25% by mass BHT; and
(g) about 0.1% by mass BHA.
11. The composition of claim 1 , wherein the soft gelatin capsule shell consists essentially of a film forming polymer, a plasticizer, and a solvent, and optionally, an opacifying agent, a coloring agent, or a pharmaceutical excipient.
12. A method for making a tamper resistant homogenous viscous yet flowable semisolid dosage form comprising:
(i) heating soybean oil to about 60° C. and adding ethylcellulose until completely dissolved to form a first clear mixture;
(ii) hydrating hydroxypropylmethylcellulose with polyethylene glycol;
(iii) mixing hydrocodone or oxycodone with the mixture of step (ii) to form a second uniform mixture; and
(iv) adding the second uniform mixture of step (iii) to the first clear mixture of (i) to form a final uniform matrix composition, and
(v) encapsulating the matrix composition of (iv) in a soft gel capsule using rotary die encapsulation.
13. A tamper resistant oral pharmaceutical composition comprising a soft gelatin capsule shell encapsulating a tamper resistant, homogenous viscous, yet flowable matrix consisting essentially of:
(a) about 50% to about 70% by mass soybean oil;
(b) about 2% to about 7% by mass ethylcellulose;
(c) about 2% to about 15% by mass hydroxypropylmethylcellulose;
(d) about 4% to about 11% by mass polyethylene glycol 400; and
(e) about 10.5% by mass of hydrocodone or oxycodone; and optionally
(f) about 0.25% by mass BHT; and
(g) about 0.1% by mass BHA.
14. A method for treating pain in a subject in need thereof, the method comprising administering the composition of claim 13 to the subject.
15. The composition of claim 1 , wherein the soft gelatin capsule shell consist essentially of:
(a) about 25% to about 50% by mass gelatin;
(b) about 15% to about 25% by mass glycerol; and
(c) about 20% to about 40% by mass water.
16. A pharmaceutical dosage form made by the method of claim 12 .
17. The composition of claim 13 , wherein the soft gelatin capsule shell consists essentially of:
(a) about 25% to about 50% by mass gelatin;
(b) about 15% to about 25% by mass glycerol; and
(c) about 20% to about 40% by mass water.