ABUSE DETERRENT COMPOSITIONS AND METHODS OF USE

1 . An orally administrable pharmaceutical composition comprising a drug, wherein the composition is configured such that when the pharmaceutical composition is administered intranasally in physically compromised form to a subject, the area under the curve (AUC) of drug after a period of time is less than 200% of the AUC of the drug achieved after oral administration of an intact form of the pharmaceutical composition after the same period of time.

2 . The orally administrable pharmaceutical composition of claim 1 , wherein the area under the curve (AUC) of drug after a period of time is less than 175% of the AUC of the drug achieved after oral administration of an intact form of the pharmaceutical composition after the same period of time.

3 . The orally administrable pharmaceutical composition of claim 1 , wherein the area under the curve (AUC) of drug after a period of time is less than 150% of the AUC of the drug achieved after oral administration of an intact form of the pharmaceutical composition after the same period of time.

4 . The orally administrable pharmaceutical composition of claim 1 , wherein the period of time is selected from the group consisting of: 0.5 hour, 1 hour, and 2 hours.

5 . The orally administrable pharmaceutical composition of claim 1 , wherein the AUC 0-t of drug after a period of time is about 100% to about 200% of the AUC 0-t of the drug achieved after oral administration of an intact form of the pharmaceutical composition after the same period of time.

6 . The orally administrable pharmaceutical composition of claim 1 , wherein the composition comprises a drug, a pH-dependent agent, and a pH-independent agent, wherein about 60% or more of the total amount of drug in the pharmaceutical composition is released after 60 minutes under the following dissolution conditions: 0.1 N HCl, 500 mL, USP Apparatus 2 (paddle), 50 rpm, 37° C.; and wherein about 25% or less of the total amount of drug in the pharmaceutical composition is released after 60 minutes under the following dissolution conditions: DI water, 500 mL, USP Apparatus 2 (Paddle), 50 rpm, 37° C.

7 . The orally administrable composition of claim 1 , wherein the composition comprises a drug, a pH-dependent agent, and a pH-independent agent, wherein no more than 50% of the total amount of drug in the pharmaceutical composition is released within 1 hour and about 50% or more of the total amount of drug in the pharmaceutical composition is released after 8 hours under the following dissolution conditions: 0.1 N HCl, 500 mL, USP Apparatus 2 (paddle), 50 rpm, 37° C.; and wherein about 25% or less of the total amount of drug in the pharmaceutical composition is released after 60 minutes under the following dissolution conditions: DI water, 500 mL, USP Apparatus 2 (Paddle), 50 rpm, 37° C.

8 . The orally administrable composition of claim 1 , wherein the drug is selected from the group consisting of: central nervous stimulants, opioids, barbiturates, benzodiazepines, and sedatives.

9 . The orally administrable pharmaceutical composition of claim 1 , wherein the drug is selected from the group consisting of alfentanil, allylprodine, alphaprodine, anileridine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, desomorphine, dextromoramide, dezocine, diampromide, diamorphone, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene, hydrocodone, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, methadone, metopon, morphine, myrophine, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, nalbuphene, normorphine, norpipanone, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, piminodine, piritramide, propheptazine, promedol, properidine, propoxyphene, sufentanil, tilidine, and tramadol.

10 . The orally administrable pharmaceutical composition of claim 1 , wherein the drug is morphine.

11 . An orally administrable pharmaceutical composition comprising 60 mg of morphine or a salt thereof, wherein the composition is configured such that when the pharmaceutical composition is administered intranasally in physically compromised form to a subject, the area under the curve (AUC) of the morphine after a period of time is less than about 400 ng·h/mL.

12 . The orally administrable pharmaceutical composition of claim 11 , wherein the composition is configured such that when the pharmaceutical composition is administered intranasally in physically compromised form to a subject, the AUC 0-t is less than about 400 ng·h/mL.

13 . The orally administrable pharmaceutical composition of claim 11 , wherein the composition is configured such that when the pharmaceutical composition is administered intranasally in physically compromised form to a subject, the AUC 0-t of the morphine is about 50 to about 300 ng·h/mL.

14 . The orally administrable composition of claim 11 , wherein the composition is configured such that when the pharmaceutical composition is administered intranasally in physically compromised form to a subject, the AUC 0-t of the morphine is about 100 to about 200 ng·h/mL.

15 . The orally administrable composition of claim 11 , wherein the composition is configured such that when the pharmaceutical composition is administered intranasally in physically compromised form to a subject, the AUC of the morphine at 0.5 hour is about 0.5 to about 8 ng·h/mL.

16 . The orally administrable composition of claim 11 , wherein the composition is configured such that when the pharmaceutical composition is administered intranasally in physically compromised form to a subject, the AUC of the morphine at 1 hour is about 2.5 to about 25 ng·h/mL.

17 . The orally administrable composition of claim 11 , wherein the composition is configured such that when the pharmaceutical composition is administered intranasally in physically compromised form to a subject, the AUC of the morphine at 2 hours is about 5 to about 75 ng·h/mL.

18 . The orally administrable composition of claim 11 , wherein the composition comprises morphine or a salt thereof, a pH-dependent agent, and a pH-independent agent, wherein about 60% or more of the total amount of drug in the pharmaceutical composition is released after 60 minutes under the following dissolution conditions: 0.1 N HCl, 500 mL, USP Apparatus 2 (paddle), 50 rpm, 37° C.; and wherein about 25% or less of the total amount of drug in the pharmaceutical composition is released after 60 minutes under the following dissolution conditions: DI water, 500 mL, USP Apparatus 2 (Paddle), 50 rpm, 37° C.

19 . The orally administrable composition of claim 11 , wherein the composition comprises morphine or a salt thereof, a pH-dependent agent, and a pH-independent agent, wherein no more than 50% of the total amount of drug in the pharmaceutical composition is released within 1 hour and about 50% or more of the total amount of drug in the pharmaceutical composition is released after 8 hours under the following dissolution conditions: 0.1 N HCl, 500 mL, USP Apparatus 2 (paddle), 50 rpm, 37° C.; and wherein about 25% or less of the total amount of drug in the pharmaceutical composition is released after 60 minutes under the following dissolution conditions: DI water, 500 mL, USP Apparatus 2 (Paddle), 50 rpm, 37° C.

20 . An orally administrable pharmaceutical composition comprising morphine or a salt thereof, wherein the composition is configured such that when the pharmaceutical composition is administered intranasally in physically compromised form to a subject, the area under the curve (AUC) of morphine after a period of time is less than about 10 ng·h/mL/mg (ng·h/mL per mg of morphine).

21 . The orally administrable composition of claim 20 , wherein the composition is configured such that when the pharmaceutical composition is administered intranasally in physically compromised form to a subject, the AUC 0-t of morphine is about 1 to about 8 ng·h/mL/mg (ng·h/mL per mg of morphine).

22 . The orally administrable composition of claim 20 , wherein the composition comprises morphine or a salt thereof, a pH-dependent agent, and a pH-independent agent, wherein about 60% or more of the total amount of drug in the pharmaceutical composition is released after 60 minutes under the following dissolution conditions: 0.1 N HCl, 500 mL, USP Apparatus 2 (paddle), 50 rpm, 37° C.; and wherein about 25% or less of the total amount of drug in the pharmaceutical composition is released after 60 minutes under the following dissolution conditions: DI water, 500 mL, USP Apparatus 2 (Paddle), 50 rpm, 37° C.

23 . The orally administrable composition of claim 20 , wherein the composition comprises morphine or a salt thereof, a pH-dependent agent, and a pH-independent agent, wherein no more than 50% of the total amount of drug in the pharmaceutical composition is released within 1 hour and about 50% or more of the total amount of drug in the pharmaceutical composition is released after 8 hours under the following dissolution conditions: 0.1 N HCl, 500 mL, USP Apparatus 2 (paddle), 50 rpm, 37° C.; and wherein about 25% or less of the total amount of drug in the pharmaceutical composition is released after 60 minutes under the following dissolution conditions: DI water, 500 mL, USP Apparatus 2 (Paddle), 50 rpm, 37° C.

24 . An orally administrable pharmaceutical composition comprising a drug, wherein the composition is configured such that when the pharmaceutical composition is administered intranasally in physically compromised form to a subject, the ratio of the area under the curve (AUC) of the drug to the AUC of a major metabolite of the drug (drug:major metabolite) achieved after a period of time is less than about 25 times the ratio of the AUC of the drug to the AUC of the major metabolite (drug:major metabolite) achieved after the same period of time after oral administration of the pharmaceutical composition in an intact form.

25 . The orally administrable pharmaceutical composition of claim 24 , wherein the AUC 0-t of the drug to the AUC 0-t of a major metabolite of the drug (drug:major metabolite) is less than about 10 times the ratio of the AUC 0-t of the drug to the AUC 0-t of the major metabolite (drug:major metabolite) after oral administration of the pharmaceutical composition in an intact form.

26 . The orally administrable composition of claim 24 , wherein the drug is selected from the group consisting of: central nervous stimulants, opioids, barbiturates, benzodiazepines, and sedatives.

27 . The orally administrable pharmaceutical composition of claim 24 , wherein the drug is selected from the group consisting of alfentanil, allylprodine, alphaprodine, anileridine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, desomorphine, dextromoramide, dezocine, diampromide, diamorphone, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene, hydrocodone, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, methadone, metopon, morphine, myrophine, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, nalbuphene, normorphine, norpipanone, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, piminodine, piritramide, propheptazine, promedol, properidine, propoxyphene, sufentanil, tilidine, and tramadol.

28 . The orally administrable pharmaceutical composition of claim 24 , wherein the drug is morphine.

29 . The orally administrable composition of claim 24 , wherein the composition comprises a drug, a pH-dependent agent, and a pH-independent agent, wherein about 60% or more of the total amount of drug in the pharmaceutical composition is released after 60 minutes under the following dissolution conditions: 0.1 N HCl, 500 mL, USP Apparatus 2 (paddle), 50 rpm, 37° C.; and wherein about 25% or less of the total amount of drug in the pharmaceutical composition is released after 60 minutes under the following dissolution conditions: DI water, 500 mL, USP Apparatus 2 (Paddle), 50 rpm, 37° C.

30 . The orally administrable composition of claim 24 , wherein the composition comprises a drug, a pH-dependent agent, and a pH-independent agent, wherein no more than 50% of the total amount of drug in the pharmaceutical composition is released within 1 hour and about 50% or more of the total amount of drug in the pharmaceutical composition is released after 8 hours under the following dissolution conditions: 0.1 N HCl, 500 mL, USP Apparatus 2 (paddle), 50 rpm, 37° C.; and wherein about 25% or less of the total amount of drug in the pharmaceutical composition is released after 60 minutes under the following dissolution conditions: DI water, 500 mL, USP Apparatus 2 (Paddle), 50 rpm, 37° C.