Methods and compositions for self-regulated release of active pharmaceutical ingredient
An abuse deterrent pharmaceutical composition including a pharmaceutically active ingredient; an acid soluble ingredient; and a buffering ingredient; wherein the acid soluble ingredient and the buffering ingredient retard release of the active pharmaceutical ingredient when the composition is ingested in excess of an intended dosage.
1. An abuse deterrent pharmaceutical composition comprising:
a particle portion, wherein the particle portion comprises:
a. a pharmaceutically active ingredient;
b. an acid soluble ingredient comprising one or more of calcium carbonate, dibasic calcium phosphate, tribasic calcium phosphate, and magnesium hydroxide; and
c. a buffering ingredient; and
a pH modifying ingredient,
wherein the pH modifying ingredient is present in an amount sufficient to inhibit dissolution of the particle portion when the abuse deterrent pharmaceutical composition is ingested in excess of a dosage appropriate to provide a therapeutic effect.
2. The abuse deterrent pharmaceutical composition of claim 1 , wherein the pH modifying ingredient is present in an amount sufficient to raise the gastrointestinal pH to greater than about 4 when the abuse deterrent pharmaceutical composition is ingested in excess of a dosage appropriate to provide a therapeutic effect.
3. The abuse deterrent pharmaceutical composition of claim 1 , wherein the pharmaceutically active ingredient comprises a drug susceptible to abuse.
4. The abuse deterrent pharmaceutical composition of claim 3 , wherein the drug susceptible to abuse comprises an opioid, a stimulant, and/or a sedative.
5. The abuse deterrent pharmaceutical composition of claim 4 , wherein the drug susceptible to abuse comprises an opioid selected from hydrocodone, hydromorphone, morphine, oxycodone, and/or salts thereof.
6. The abuse deterrent pharmaceutical composition of claim 1 , wherein the acid soluble ingredient and the pH modifying ingredient are the same ingredient.
7. The abuse deterrent pharmaceutical composition of claim 1 , wherein the pH modifying ingredient comprises one or more of aluminum hydroxide, bismuth aluminate, bismuth carbonate, bismuth subcarbonate, bismuth subgallate, bismuth subnitrate, calcium carbonate, calcium phosphate, dibasic calcium phosphate, tribasic sodium phosphate, dihydroxyaluminum aminoacetate, dihydroxyaluminum sodium carbonate, glycine, magnesium glycinate, magnesium hydroxide, magnesium oxide, potassium bicarbonate, sodium bicarbonate, sodium potassium tartrate, tricalcium phosphate, and magnesium hydroxide.
8. The abuse deterrent pharmaceutical composition of claim 1 , further comprising a disintegrant.
9. The abuse deterrent pharmaceutical composition of claim 8 , wherein the disintegrant comprises sodium starch glycolate.
10. The abuse deterrent pharmaceutical composition of claim 1 , further comprising a lubricant.
11. The abuse deterrent pharmaceutical composition of claim 10 , wherein the lubricant comprises one or more of stearic acid, magnesium stearate, hydrogenated oil, sodium stearyl fumarate, and polyethylene glycol.
12. The abuse deterrent pharmaceutical composition of claim 1 , further comprising a cationic copolymer comprising dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate.
13. The abuse deterrent pharmaceutical composition of claim 12 , wherein the cationic copolymer is soluble in acid and insoluble above pH 5.
14. The abuse deterrent pharmaceutical composition of claim 1 , wherein the acid soluble ingredient and the pH modifying ingredient retard release of the pharmaceutically active ingredient when the composition is ingested in excess of a dosage appropriate to provide a therapeutic effect.
15. The abuse deterrent pharmaceutical composition of claim 14 , wherein the abuse deterrent composition is in the form of a unit dose.
16. The abuse deterrent pharmaceutical composition of claim 15 , wherein the unit dose is a capsule.
17. The abuse deterrent pharmaceutical composition of claim 15 , wherein the unit dose is a tablet.
18. The abuse deterrent pharmaceutical composition of claim 15 , wherein excess of a dosage appropriate to provide a therapeutic effect is three unit doses or greater.
19. The abuse deterrent pharmaceutical composition of claim 1 , wherein the acid soluble ingredient sequesters the pharmaceutically active ingredient from the pH modifying ingredient.
20. The abuse deterrent pharmaceutical composition of claim 19 , wherein the acid soluble ingredient sequesters the pharmaceutically active ingredient from the pH modifying ingredient by coating the pharmaceutically active ingredient.
21. The abuse deterrent pharmaceutical composition of claim 1 , wherein the particle portion is sequestered from the pH modifying ingredient by a polymeric coating comprising a copolymer based on methyl methacrylate.
22. The abuse deterrent pharmaceutical composition of claim 1 , wherein the particle portion further comprises a cationic copolymer.
23. The abuse deterrent pharmaceutical composition of claim 22 , wherein the cationic copolymer comprises a methyl methacrylate copolymer.