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 oral dosage form comprising:
preparing a mixture comprising oxycodone or a pharmaceutically acceptable salt thereof, a copolymer comprising trimethyl ammonioethyl methacrylate, and a gelling agent comprising polyethylene oxide and microcrystalline cellulose;
formulating the mixture into a matrix;
coating the matrix with a mixture comprising an aminoalkyl methacrylate copolymer, sodium lauryl sulfate, talc and simethicone;
wherein the oxycodone or pharmaceutically acceptable salt thereof is the sole active agent in the dosage form,
the abuse deterrent dosage form forming 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 oxycodone or pharmaceutically acceptable salt thereof from about 8:1 to about 1:8; and
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 gelling agent is in an effective amount to impart a viscosity of about 10 cP or more to the gel.
3. The method of claim 1 , wherein the gelling agent is in an effective amount to impart a viscosity of about 60 cP or more to the gel.
4. The method of claim 1 , wherein the gelling agent is in an effective amount to impart a viscosity of about 120 cP or more to the gel.
5. The method of claim 1 , wherein the gelling agent is in an effective amount to impart a viscosity of about 2,000 cP or more to the gel.
6. The method of claim 1 , wherein the dosage form subjected to tampering is unsuitable for injection with an insulin syringe.
7. The method of claim 1 , wherein the dosage form subjected to tampering is difficult to pull into an insulin syringe.
8. The method of claim 1 , wherein the dosage form subjected to tampering cannot be filled into an insulin syringe without picking up pockets of air.
9. The method of claim 1 , wherein the dosage form subjected to tampering has a milk like color.
10. The method of claim 1 , wherein the aqueous liquid is water.
11. The method of claim 1 , 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.
12. The method of claim 3 , wherein the gel is formed when the dosage form is subjected to tampering comprising crushing and dissolution in the aqueous liquid.
13. The method of claim 1 , wherein the gel is formed when the dosage form is subjected to tampering comprising dissolution in the aqueous liquid at ambient temperature.
14. The method of claim 1 , 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.
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. The method of claim 1 , wherein the ratio of gelling agent to oxycodone or pharmaceutically acceptable salt thereof is from about 1:1 to about 8:1.
19. A method of preparing an abuse deterrent controlled release oral dosage form comprising:
preparing a mixture comprising oxycodone or a pharmaceutically acceptable salt thereof, a copolymer comprising trimethyl ammonioethyl methacrylate, and a gelling agent comprising polyethylene oxide and microcrystalline cellulose;
formulating the mixture into a matrix;
coating the matrix with a mixture comprising an aminoalkyl methacrylate copolymer, sodium lauryl sulfate, talc and simethicone;
wherein the oxycodone or pharmaceutically acceptable salt thereof is the sole active agent in the dosage form,
the abuse deterrent dosage form forming 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 oxycodone or pharmaceutically acceptable salt thereof from about 1:1 to about 1:8; and
the dosage form providing a therapeutic effect for about 12 hours or longer when orally administered to a human patient.
20. The method of claim 19 , wherein the gelling agent is in an effective amount to impart a viscosity of about 60 cP or more to the gel.
21. The method of claim 19 , wherein the polyethylene oxide has a weight average molecular weight from about 100,000 daltons to about 1,000,000 daltons.
22. The method of claim 19 , wherein the polyethylene oxide has a weight average molecular weight from about 1,000,000 daltons to about 10,000,000 daltons.