ABUSE DETERRENT COMPOSITIONS AND METHODS OF USE
Orally administrable pharmaceutical compositions, methods of administration, and methods of making the same are provided. The pharmaceutical compositions provide abuse deterrent properties.
1 . An orally administrable pharmaceutical composition in unit dosage form comprising 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.
2 . The orally administrable pharmaceutical composition of claim 1 , wherein about 70% 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.
3 . The orally administrable pharmaceutical composition of claim 1 , wherein about 80% 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.
4 . The orally administrable pharmaceutical composition of claim 1 , wherein about 15% 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.
5 . The orally administrable pharmaceutical composition of claim 1 , wherein about 10% 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.
6 . The orally administrable pharmaceutical composition of claim 1 , wherein the drug is selected from the group consisting of: central nervous stimulants, opioids, barbiturates, benzodiazepines, and sedatives.
7 . 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, papavereturn, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, piminodine, piritramide, propheptazine, promedol, properidine, propoxyphene, sufentanil, tilidine, and tramadol.
8 . The orally administrable pharmaceutical composition of claim 1 , wherein the pH-independent agent is selected from the group consisting of: hydroxyethyl cellulose polymers, ethylcellulose polymers, methylcellulose polymers, hydroxypropyl methylcellulose polymers; methacrylate/acrylate copolymers with trimethyl-ammonioethyl-amethacylate as a functional group, and neutral polymers of methacrylate/acrylates.
9 . The orally administrable pharmaceutical composition of claim 1 , wherein the pH-dependent agent is selected from the group consisting of: cationic polymers with a dimethylaminoethyl ammonium group and poly(butyl methacrylate-co-(2-demethylaminoeethyl)methacrylate-co-methyl methacrylate), 1:2:1.
10 . The orally administrable pharmaceutical composition of claim 1 , wherein the weight ratio of pH-dependent agent to pH-independent agent (pH-dependent agent:pH-independent agent) is about 50:1 to 1:50.
11 . The orally administrable pharmaceutical composition of claim 1 , wherein the weight ratio of pH-dependent agent to pH-independent agent (pH-dependent agent:pH-independent agent) is about 25:1 to 1:25.
12 . The orally administrable pharmaceutical composition of claim 1 , wherein the weight ratio of pH-dependent agent to pH-independent agent (pH-dependent agent:pH-independent agent) is about 10:1 to 1:1.
13 . The orally administrable pharmaceutical composition of claim 1 , wherein the unit dosage form is selected from the group consisting of: tablets, capsules, microcapsules, granules, pellets, lollipops, and lozenges.
14 . An orally administrable pharmaceutical composition in unit dosage form comprising 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.
15 . The orally administrable pharmaceutical composition of claim 14 , wherein about 60% or more of the total amount of drug in the pharmaceutical composition is released after 8 hours under the following dissolution conditions: 0.1N HCl, 500 mL, USP Apparatus 2 (paddle), 50 rpm, 37° C.
16 . The orally administrable pharmaceutical composition of claim 14 , wherein about 70% or more of the total amount of drug in the pharmaceutical composition is released after 8 hours under the following dissolution conditions: 0.1N HCl, 500 mL, USP Apparatus 2 (paddle), 50 rpm, 37° C.
17 . The orally administrable pharmaceutical composition of claim 14 , wherein about 15% 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.
18 . The orally administrable pharmaceutical composition of claim 14 , wherein about 10% 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 pharmaceutical composition of claim 14 , wherein the drug is selected from the group consisting of: central nervous stimulants, opioids, barbiturates, benzodiazepines, and sedatives.
20 . The orally administrable pharmaceutical composition of claim 14 , 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, papavereturn, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, piminodine, piritramide, propheptazine, promedol, properidine, propoxyphene, sufentanil, tilidine, and tramadol.
21 . The orally administrable pharmaceutical composition of claim 14 , wherein the pH-independent agent is selected from the group consisting of: hydroxyethyl cellulose polymers, ethylcellulose polymers, methylcellulose polymers, hydroxypropyl methylcellulose polymers; methacrylate/acrylate copolymers with trimethyl-ammonioethyl-amethacylate as a functional group, and neutral polymers of methacrylate/acrylates.
22 . The orally administrable pharmaceutical composition of claim 1 , wherein the pH-dependent agent is selected from the group consisting of: cationic polymers with a dimethylaminoethyl ammonium group and poly(butyl methacrylate-co-(2-demethylaminoeethyl)methacrylate-co-methyl methacrylate), 1:2:1.
23 . The orally administrable pharmaceutical composition of claim 14 , wherein the weight ratio of pH-dependent agent to pH-independent agent (pH-dependent agent:pH-independent agent) is about 50:1 to 1:50.
24 . The orally administrable pharmaceutical composition of claim 14 , wherein the weight ratio of pH-dependent agent to pH-independent agent (pH-dependent agent:pH-independent agent) is about 25:1 to 1:25.
25 . The orally administrable pharmaceutical composition of claim 14 , wherein the weight ratio of pH-dependent agent to pH-independent agent (pH-dependent agent:pH-independent agent) is about 10:1 to 1:1.
26 . The orally administrable pharmaceutical composition of claim 14 , wherein the unit dosage form is selected from the group consisting of: tablets, capsules, microcapsules, granules, pellets, lollipops, and lozenges.