Tamper resistant pharmaceutical formulations
Disclosed in certain embodiments is a solid oral dosage form comprising a heat-labile gelling agent; a thermal stabilizer; and a drug susceptible to abuse.
1. A solid oral dosage form comprising a
a heat-labile gelling agent;
a thermal stabilizer;
hydrocodone or a pharmaceutically acceptable salt thereof;
acetaminophen; and
a pH-modifying agent that provides a pH of between about 5.5 and 8.5 to a viscous solution obtained when the dosage form is crushed and mixed with 5 mL of distilled water.
2. The solid oral dosage form of claim 1 , wherein the heat-labile gelling agent is a polymer.
3. The solid oral dosage form of claim 2 , wherein the polymer is a polysaccharide.
4. The solid oral dosage form of claim 3 , wherein the polysaccharide is a microbial polysaccharide.
5. The solid oral dosage form of claim 4 , wherein the microbial polysaccharide is xanthan gum.
6. The solid oral dosage form of claim 1 , wherein the thermal stabilizer is a gelling agent different than the heat-labile gelling agent.
7. The solid oral dosage form of claim 6 , wherein the thermal stabilizer gelling agent is a polymer.
8. The solid oral dosage form of claim 7 , wherein the thermal stabilizer gelling agent polymer is an anionic polymer in a neutral pH aqueous solution.
9. The solid oral dosage form of claim 8 , wherein the anionic polymer is a polyacrylic acid.
10. The solid oral dosage form of claim 9 , wherein the polymer is carbomer homopolymer.
11. The solid oral dosage form of claim 10 , wherein the heat-labile gelling agent is a polysaccharide.
12. The solid oral dosage form of claim 11 , wherein the polysaccharide is a microbial polysaccharide.
13. The solid oral dosage form of claim 1 , wherein the heat-labile gelling agent is xanthan gum and the thermal stabilizer is carbomer homopolymer.
14. The solid oral dosage form of claim 1 , wherein the viscosity of the solid oral dosage form after crushing and mixing with from about 0.5 to about 10 ml of distilled water prevents the hydrocodone or a pharmaceutically acceptable salt thereof from being systemically absorbed, or reduces the ability of the hydrocodone or a pharmaceutically acceptable salt thereof to be systemically absorbed, when administered by the parenteral or nasal route.
15. The solid oral dosage form of claim 1 , wherein the dosage form releases at least about 85% of the hydrocodone or a pharmaceutically acceptable salt thereof within 45 minutes as measured by in-vitro dissolution in a USP Apparatus 2 (paddle) at 50 rpm in 500 ml SGF at 37° C.
16. The solid oral dosage form of claim 1 , comprising hydrocodone bitartrate.
17. The solid oral dosage form of claim 15 , comprising from about 2.5 mg to about 15 mg hydrocodone or a pharmaceutically acceptable salt thereof and from about 325 mg to about 650 mg acetaminophen.