Compositions and methods for reducing overdose

1. A unit dose formulation comprising:

at least one active substance;

at least one acid labile coat surrounding said at least one active substance; and

at least one alkalinizing coat surrounding said at least one acid labile coat,

wherein said at least one alkalinizing coat is present in an amount sufficient to raise the pH of the stomach, such that dissolution of said at least one acid labile coat and release of said at least one active substance is inhibited when the number of unit dosage forms ingested exceeds a predetermined number.

2. The unit dose formulation of claim 1 , further comprising a core, the core comprising said at least one active substance; and said at least one acid labile coat surrounding said core.

3. The unit dose formulation of claim 1 , further comprising a core and at least one coat, said at least one coat comprising said at least one active substance; and said at least one acid labile coat surrounding said at least one coat.

4. The unit dose formulation of claim 1 , wherein the predetermined number is less than 20.

5. The unit dose formulation of claim 4 , wherein the predetermined number is 1, 2, 3, 4, or 5.

6. The unit dose formulation of claim 5 , wherein the predetermined number is 1 or 2.

7. The unit dose formulation of claim 1 , wherein, when the number of unit dosage forms ingested exceeds a predetermined number, said at least one alkalinizing coat increases stomach pH to inhibit dissolution of said at least one acid labile substance and inhibit release of said at least one active substance.

8. The unit dose formulation of claim 1 , wherein each of said at least one alkalinizing coat comprises at least one alkalinizing agent.

9. The unit dose formulation of claim 1 , wherein said at least one alkalinizing agent is present in said at least one alkalinizing coat in an amount such that:

when less than a predetermined number of unit dose formulations is ingested, the gastric pH remains sufficiently acidic to dissolve said at least one acid labile coat and/or substance and release said at least one active substance; and

when more than the predetermined number of the unit dose formulations is ingested, the gastric pH is alkalinized sufficiently to inhibit dissolution of said at least one acid labile coat and/or substance and release of said at least one active substance.

10. The unit dose formulation of claim 9 , wherein the predetermined number is 2, 3, 4, or 5.

11. The unit dose formulation of claim 10 , wherein the predetermined number is 2.

12. The unit dose formulation of claim 9 , wherein said at least one alkalinizing agent is selected from the group consisting of alkaline earth metal salts, alkali metal salts, aluminum salts, amino acids, amino acid derivatives, and combinations thereof.

13. The unit dose formulation of claim 9 , wherein said at least one alkalinizing agent is selected from the group consisting of magnesium hydroxide, magnesium trisilicate, aluminum hydroxide, magnesium oxide, calcium carbonate, sodium bicarbonate, sodium citrate, sodium carbonate, sodium acetate, magnesium carbonate, L-arginine, meglumine, and combinations thereof.

14. The unit dose formulation of claim 13 , wherein said at least one alkalinizing agent is magnesium hydroxide.

15. The unit dose formulation of claim 1 , wherein each of said at least one acid labile coat comprises at least one acid labile substance.

16. The unit dose formulation of claim 15 , wherein said at least one acid labile substance is selected from the group consisting of sulfonamide-based polymers and copolymers, amine functional polymers such as polyvinyl pyridine polymers and copolymers, polysaccharides such as chitosan, poly(vinylpyrrolidone-co-dimethylmaleic anhydride) (PVD), dimethylaminoethyl methacrylate copolymers such as Eudragit E, Eudragit E interpolyelectrolyte complex, Eudragit E polyamopholyte complex, Eudragit E interpolyelectrolyte complex with Eudragit L and/or Eudragit S, derivatives thereof, and combinations thereof.

17. The unit dose formulation of claim 15 , wherein said at least one acid labile coat and/or substance comprises Eudragit E.

18. The unit dose formulation of claim 1 , wherein said at least one acid labile coat and/or acid labile substance dissolves in a solution with a pH of less than about 6, 5, 4, 3, 2, or 1.

19. The unit dose formulation of claim 1 , wherein dissolution of said at least one acid labile coat and/or acid labile substance is inhibited in a solution with a pH of greater than about 3, 4, 5, or 6.

20. The unit dose formulation of claim 1 , wherein said at least one acid labile coat and/or said acid labile substance is soluble in stomach pH.

21. The unit dose formulation of claim 1 , wherein said at least one alkalinizing coat has at least one alkalinizing agent in an amount of at least about 1 mg per unit dosage formulation but such that when more unit dosage formulations than prescribed are swallowed at once, the pH of the stomach changes to an alkaline pH and release of said at least one active substance is inhibited.

22. The unit dose formulation of claim 21 , wherein the number of unit dosage formulations than that prescribed is about 1 to about 100 and the stomach pH is less than about 5, the pH of the stomach changes to alkaline pH.

23. The unit dose formulation of claim 2 , wherein the core further comprises at least one disintegrant, at least one Eudragit RL and Eudragit RS, at least one coloring agent, and at least one polyethylene oxide.

24. The unit dose formulation of claim 23 , wherein the core comprises an outer active substance-releasing coat beneath said at least one alkalinizing coat.

25. The unit dose formulation of claim 2 , wherein the core comprises a plurality of compressed granules.

26. The unit dose formulation of claim 2 , further comprising at least one agent selected from the group consisting of an abuse deterrent coloring agent; a controlled release agent; a viscosity imparting agent; a gelling agent; polyethylene oxide; crospovidone; Eudragit RL; Eudragit RS, and combinations thereof.

27. The unit dose formulation of claim 26 , wherein said at least one agent is said at least one abuse deterrent coloring agent.

28. The unit dose formulation of claim 26 , wherein said at least one abuse deterrent coloring agent is brilliant blue.

29. The unit dose formulation of claim 1 , further comprising at least one agent selected from the group consisting of a chewing discouraging agent, a licking discouraging agent, an insufflation discouraging agent, a snorting discouraging agent, an inhalation discouraging agent, and combinations thereof.

30. The unit dose formulation of claim 29 , wherein the discouraging agent is selected from the group consisting of a coloring agent, a tussigenic agent, an irritant, and combinations thereof.

31. The unit dose formulation of claim 1 , wherein said at least one active substance is at least one addictive substance.

32. The unit dose formulation of claim 1 , wherein said at least one active substance is at least one opioid agonist and/or at least one narcotic analgesic.

33. The unit dose formulation of claim 1 , wherein said at least one active substance has an analgesic ceiling effect.

34. The unit dose formulation of claim 1 , in the form of a bead, tablet, capsule, granule, and/or pellet.

35. The unit dose formulation of claim 1 , wherein said at least one active substance is in an amount of from about 0.1 mg to about 1000 mg; said at least one acid labile coat is in an amount of from about 0.5 mg to about 500 mg; and/or said at least one alkalinizing coat is in an amount of from about 0.5 mg to about 500 mg.

36. The unit dose formulation of claim 1 , wherein said at least one acid labile coat is present in an amount of from 0.5 mg/cm 2 to 200 mg/cm 2 or from 1 mg/cm 2 to 100 mg/cm 2 or from 2 mg/cm 2 to 150 mg/cm 2 or from about 4 mg/cm 2 to about 100 mg/cm 2 or from 8 mg/cm 2 to 50 mg/cm 2 .

37. The unit dose formulation of claim 1 , wherein said at least one acid labile substance is present in an amount that yields from about 1% to about 200% weight gain, from about 1% to about 70% or from about 1% to about 50% weight gain.

38. The unit dose formulation of claim 1 , wherein said at least one alkalinizing coat has a thickness of from about 2 mg/cm 2 to about 100 mg/cm 2 , or 15 mg/cm 2 to about 55 mg/cm 2 , or 10 mg/cm 2 to about 40 mg/cm 2 , or 40 mg/cm 2 to about 80 mg/cm 2 , or 80 mg/cm 2 to about 100 mg/cm 2 .

39. The unit dose formulation of claim 1 , wherein said at least one alkalinizing coat is present in an amount that yields from about 1% to about 200% weight gain, from about 5% to about 80%, from about 1% to about 70% weight gain, from about 1% to about 50% or from about 5% to about 50% weight gain.

40. The unit dose formulation of claim 1 , wherein said at least one alkalinizing coat is partially, substantially or completely surrounding.

41. The unit dose formulation of claim 1 , wherein said at least one acid labile coat is substantially or completely surrounding.

42. The unit dose formulation of claim 1 , wherein the unit dose formulation is an immediate release or controlled release medication.

43. The unit dose formulation of claim 1 , wherein the alkalinizing coat contains at least one alkalinizing agent that is capable of undergoing the following neutralization with stomach acid:

MX 2 +2HCl→MCl 2 +2HX or MX 3 +3HCl→MCl 3 +3HX

where M is a metal ion and X is a basic ion.

44. The unit dose formulation of claim 1 , wherein said at least one active.

45. The unit dose formulation of claim 1 , wherein said at least one active comprises multivitamins, Acetominophen, Aspirin, Oxycodone, Hydrocodone, Oxymorphone, Hydromorphone, Morphine, Codeine, and combinations thereof.

46. The unit dose formulation of claim 1 , wherein when more than the recommended dose is ingested at once, an insignificant amount or less of said at least one active substance is released.

47. The unit dose formulation of claim 1 , wherein when more than the recommended dose is ingested at once, there is a lag time before a significant amount of said at least one active substance is released.

48. The unit dose formulation of claim 1 , wherein when between 2 to 10 unit dose forms, or between 11 to 20 unit dose forms, or between 21 to 30 unit dose forms, or between 31 to 40 unit dose forms, or between 41 to 50 unit dose forms, or between 51 to 100 unit dose forms are swallowed intact, the formulation delays, reduces or prevents the instantaneous release of all or significant amounts of said at least one active substance.

49. The formulation of claim 1 , wherein the pharmacokinetic profile on single dosage administration during fasting and/or feed conditions shows a high rate of input of said at least one active substance in the first hour which is at least 5 times the rate of input of said at least one active substance at subsequent hourly intervals.

50. The formulation of claim 1 , wherein said formulation is about 40 mg oxycodone hydrochloride form wherein the pharmacokinetic profile on single dose administration shows a mean plasma concentration per unit of time of between about 15 ng/ml and about 35 ng/ml between about the first hour and about the sixth hour.

51. A capsule comprising the unit dose formulation of claim 1 .

52. The unit dose formulation of claim 1 , wherein said at least one active substance is an over the counter (OTC) medication.