Pharmaceutical formulation containing gelling agent
Disclosed in certain embodiments is a controlled release oral dosage form comprising a therapeutically effective amount of a drug susceptible to abuse together with one or more pharmaceutically acceptable excipients; the dosage form further including a gelling agent in an effective amount to impart a viscosity unsuitable for administration selected from the group consisting of parenteral and nasal administration to a solubilized mixture formed when the dosage form is crushed and mixed with from about 0.5 to about 10 ml of an aqueous liquid; the dosage form providing a therapeutic effect for at least about 12 hours when orally administered to a human patient.
1. A method of preparing an abuse deterrent controlled release dosage form comprising:
preparing a mixture comprising an opioid agonist and a gelling agent comprising polyethylene oxide, polyethylene glycol and hydroxypropylmethylcellulose;
heating the mixture to a temperature to at least soften the mixture;
extruding the heated mixture to form an extrudate;
formulating the extrudate into a tablet; and
coating the tablet with a coating comprising polyvinyl alcohol polyethylene glycol and talc,
wherein the opioid agonist is the sole active agent in the dosage form; and wherein the dosage form forms a gel when subjected to tampering comprising dissolution in from about 0.5 ml to about 10 ml of an aqueous liquid;
the dosage form having a ratio of gelling agent to opioid agonist from about 8:1 to about 1:8;
the dosage form providing a therapeutic effect for about 12 hours or longer when orally administered to a human patient.
2. The method of claim 1 , wherein the mixture further comprises alpha-tocopherol.
3. The method of claim 2 , wherein the dosage form subjected to tampering is unsuitable for injection with an insulin syringe.
4. The method of claim 2 , wherein the dosage form subjected to tampering is difficult to pull into an insulin syringe.
5. The method of claim 2 , wherein the dosage form subjected to tampering cannot be filled into an insulin syringe without picking up pockets of air.
6. The method of claim 2 , wherein the dosage form subjected to tampering has a milk like color.
7. The method of claim 2 , wherein the aqueous liquid is water.
8. The method of claim 2 , wherein the gel is formed when the dosage form is subjected to tampering comprising dissolution in about 1 ml to about 3 ml of aqueous liquid.
9. The method of claim 2 , wherein the gel is formed when the dosage form is subjected to tampering comprising crushing and dissolution in the aqueous liquid.
10. The method of claim 2 , wherein the gel is formed when the dosage form is subjected to tampering comprising dissolution in the aqueous liquid at ambient temperature.
11. The method of claim 2 , wherein the gel is formed when the dosage form is subjected to tampering comprising dissolution in the aqueous liquid with heating greater than 45° C.
12. The method of claim 2 , wherein the gelling agent is in an effective amount to impart a viscosity of about 10 cP or more to the gel.
13. The method of claim 2 , wherein the gelling agent is in an effective amount to impart a viscosity of about 60 cP or more to the gel.
14. The method of claim 2 , wherein the gelling agent is in an effective amount to impart a viscosity of about 120 cP or more to the gel.
15. The method of claim 1 , wherein the gelling agent is in an effective amount to impart a viscosity from about 120 cP to about 5,000 cP to the gel.
16. The method of claim 1 , wherein the polyethylene oxide has a weight average molecular weight from about 100,000 daltons to about 1,000,000 daltons.
17. The method of claim 1 , wherein the polyethylene oxide has a weight average molecular weight from about 1,000,000 daltons to about 10,000,000 daltons.
18. A method of preparing an abuse deterrent controlled release dosage form comprising:
preparing a mixture comprising an opioid agonist and a gelling agent comprising polyethylene oxide, hydroxypropylmethylcellulose and polyethylene glycol; and
heating the mixture to a temperature to at least soften the mixture;
extruding the heated mixture to form an extrudate;
formulating the extrudate into a tablet; and
coating the tablet with a coating comprising polyvinyl alcohol, polyethylene glycol and talc,
wherein the opioid agonist is the sole active agent in the dosage form; and wherein the dosage form forms a gel when subjected to tampering comprising dissolution in from about 0.5 ml to about 10 ml of an aqueous liquid;
the dosage form having a ratio of gelling agent to opioid agonist from about 8:1 to about 1:1;
the dosage form providing a therapeutic effect for about 12 hours or longer when orally administered to a human patient.
19. The method of claim 1 , wherein the ratio of gelling agent to opioid agonist is from about 3:1 to about 1:1.
20. The method of claim 18 , wherein the mixture further comprises alpha-tocopherol.
21. The method of claim 18 , wherein the aqueous liquid is water.
22. The method of claim 21 , wherein the gel is formed when the dosage form is subjected to tampering comprising crushing and dissolution in the water.
23. The method of claim 21 , wherein the gel is formed when the dosage form is subjected to tampering comprising dissolution in the water with heating greater than 45° C.
24. The method of claim 21 , wherein the gelling agent is in an effective amount to impart a viscosity of about 10 cP or more to the gel.