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 method of treating pain comprising administering to a patient in need thereof, a solid oral dosage form comprising:
a heat-labile gelling agent;
a thermal stabilizer comprising an anionic polymer in a neutral pH aqueous solution; and
an analgesic drug susceptible to abuse,
wherein the solid oral dosage form releases at least about 85% of the drug susceptible to abuse 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.
2. The method of claim 1 , wherein the heat-labile gelling agent is a polymer.
3. The method of claim 2 , wherein the polymer is a polysaccharide.
4. The method of claim 3 , wherein the polysaccharide is a microbial polysaccharide.
5. The method of claim 4 , wherein the microbial polysaccharide is xanthan gum.
6. The method of claim 1 , wherein the thermal stabilizer is a polyacrylic acid.
7. The method of claim 6 , wherein the polyacrylic acid is a carbomer homopolymer.
8. The method of claim 1 , wherein the heat-labile gelling agent is xanthan gum and wherein the thermal stabilizer is a carbomer homopolymer.
9. The method of claim 1 , further comprising a pH-modifying agent.
10. The method of claim 9 , wherein the pH-modifying agent 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.
11. The method of claim 1 , further comprising a disintegrant.
12. The method of claim 1 , further comprising a filler.
13. The method of claim 1 , wherein the filler is selected from the group consisting of lactose, dextrose, mannitol, microcrystalline cellulose and a mixture thereof.
14. The method of claim 1 , comprising the heat-labile gelling agent in an amount from 0.25% to about 75% (w/w) of the dosage form.
15. The method of claim 1 , comprising the thermal stabilizer in an amount from about 0.25% to about 90% (w/w) of the dosage form.
16. The method of claim 1 , further comprising an aversive agent.
17. The method of claim 16 , wherein the aversive agent is an irritant comprising one or more of a surfactant, capsaicin or a capsaicin analog.
18. The method of claim 1 , wherein the analgesic drug is an opioid agonist selected from the group consisting of codeine, morphine, oxycodone, oxymorphone, hydrocodone, hydromorphone, pharmaceutically acceptable salts thereof, and mixtures thereof.
19. The method of claim 1 , wherein the ratio of the heat-labile gelling agent to the thermal stabilizer is from about 1:5 to about 5:1 (w/w).
20. The method of claim 1 , wherein the ratio of the analgesic drug to the heat-labile gelling agent is from about 1:40 to about 40:1 (w/w).