Formulations comprising a denatonium salt for preventing malicious drug use

Abstract

Provided herein are pharmaceutical compositions comprising a denatonium salt and a pharmaceutical agent. Also provided herein are methods for reducing a risk of drug abuse comprising use of a denatonium salt to decrease the likelihood of improper ingestion of a pharmaceutical agent. Also provided herein are methods for making the test of a drug less palatable comprising a subclinical dose of a denatonium salt.

Description

[0001] Attorney Docket No.01309-0014-00PCT FORMULATIONS COMPRISING A DENATONIUM SALT FOR PREVENTING MALICIOUS DRUG USE CROSS-REFERENCE TO RELATED APPLICATIONS [1] This application claims the benefit of priority of US Provisional Application No. 63 / 678,417, filed on August 1, 2024, which is incorporated by reference herein in its entirety for all purposes. FIELD OF THE INVENTION [2] The present disclosure provides pharmaceutical compositions comprising a denatonium salt and a pharmaceutical agent. The present disclosure also provides methods for reducing a risk of drug abuse comprising use of a denatonium salt to decrease the likelihood of improper ingestion of a pharmaceutical agent. The present disclosure also provides methods for making the taste of a drug less palatable comprising a subclinical dose of a denatonium salt. INTRODUCTION AND SUMMARY [3] Drug-facilitated sexual assault (DFSA) is a present and ever-growing problem, which spreads in public bars and pubs and other social event venues around the world, whereas these drugs can be used in any context, not just in a dating setting. “Date rape drugs,” (DRDs) are drugs that are slipped into someone's drink without their knowledge or consent. These drugs can cause a variety of effects, including impaired judgment, anterograde amnesia (the inability to form new memories), or sedation, all of which make the victim more vulnerable to sexual assault. [4] Other classes of drugs are also susceptible to abuse. Non-limiting examples include, but are not limited to, agents that cause drowsiness, agents that depress the central nervous system, opioids, and narcotics. [5] Thus, there is a need for pharmaceutical compositions and methods that reduce the risk of drug abuse, drug-facilitated sexual assault (i.e., date rape), and / or other crime, and to decrease the likelihood of improper ingestion of a pharmaceutical agent by, e.g., making the taste of a pharmaceutical agent detectable and / or less palatable. Attorney Docket No.01309-0014-00PCT [6] The present disclosure provides pharmaceutical compositions and methods to meet at least one of the foregoing needs, provide other benefits, or at least provide the public with a useful choice. Accordingly, the disclosure includes the following embodiments. [7] In exemplary embodiments, a denatonium salt is included in a pharmaceutical composition such that the bitter taste of the denatonium salt is detectable when the pharmaceutical composition is surreptitiously added to a drink, food, or other consumable, but the bitter taste is not detectable when the pharmaceutical composition is intentionally self- administered (e.g., by swallowing an oral solid dosage form). [8] Embodiment 1 is a pharmaceutical composition comprising a denatonium salt and a pharmaceutical agent, wherein the pharmaceutical agent is used, or is capable of being used, for drug-facilitated sexual assault or other crime and / or comprises an agent that causes drowsiness, an agent that depresses the central nervous system, an agent that alters consciousness, an agent that impairs decision making, an agent that lowers inhibitions, an opioid, a narcotic, a psychoactive depressant, a sedative, a hypnotic, an anxiolytic, the benzodiazepine or non- benzodiazepine class or z-drug, an anti-psychotic, a stimulant, a hallucinogen, a euphoriant, an anti-cholinergic, an anti-histamine, or an anesthetic. [9] Embodiment 2 is the pharmaceutical composition of any one of the preceding embodiments, wherein the denatonium salt comprises denatonium acetate, denatonium citrate, denatonium tartrate, denatonium maleate, or denatonium saccharide.

[0010] Embodiment 3 is the pharmaceutical composition of any one of the preceding embodiments, wherein the denatonium salt comprises denatonium acetate.

[0011] Embodiment 4 is the pharmaceutical composition of any one of the preceding embodiments, wherein the denatonium salt comprises denatonium acetate monohydrate.

[0012] Embodiment 5 is the pharmaceutical composition of any one of the preceding embodiments, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 50 mg.

[0013] Embodiment 5.1 is the pharmaceutical composition of embodiment 5, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 5 mg. Attorney Docket No.01309-0014-00PCT

[0014] Embodiment 5.2 is the pharmaceutical composition of embodiment 5, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 mg to about 10 mg.

[0015] Embodiment 5.3 is the pharmaceutical composition of embodiment 5, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 mg to about 20 mg.

[0016] Embodiment 5.4 is the pharmaceutical composition of embodiment 5, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20 mg to about 30 mg.

[0017] Embodiment 5.5 is the pharmaceutical composition of embodiment 5, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30 mg to about 40 mg.

[0018] Embodiment 5.6 is the pharmaceutical composition of embodiment 5, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 40 mg to about 50 mg.

[0019] Embodiment 6 is the pharmaceutical composition of any one of the preceding embodiments, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 to 100 parts per million by weight or 0.01 to 0.1 milligrams per milliliter.

[0020] Embodiment 6.1 is the pharmaceutical composition of any one of embodiments 1-5, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.05 to 1 part per million by weight.

[0021] Embodiment 6.2 is the pharmaceutical composition of Embodiment 6.1, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.1 to 1 part per million by weight.

[0022] Embodiment 6.3 is the pharmaceutical composition of Embodiment 6.1, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.1 to 0.5 part per million by weight. Attorney Docket No.01309-0014-00PCT

[0023] Embodiment 6.4 is the pharmaceutical composition of Embodiment 6.1, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.5 to 1 part per million by weight.

[0024] Embodiment 7 is the pharmaceutical composition of embodiment 6, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 part per million by weight.

[0025] Embodiment 8 is the pharmaceutical composition of embodiment 6, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 2 parts per million by weight.

[0026] Embodiment 9 is the pharmaceutical composition of embodiment 6, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 parts per million by weight.

[0027] Embodiment 10 is the pharmaceutical composition of embodiment 6, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 parts per million by weight.

[0028] Embodiment 10.01 is the pharmaceutical composition of embodiment 6, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10-20 parts per million by weight.

[0029] Embodiment 10.02 is the pharmaceutical composition of embodiment 6, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20-30 parts per million by weight.

[0030] Embodiment 10.03 is the pharmaceutical composition of embodiment 6, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30-40 parts per million by weight.

[0031] Embodiment 10.04 is the pharmaceutical composition of embodiment 6, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the Attorney Docket No.01309-0014-00PCT denatonium salt is present in said composition in a dose of about 40-50 parts per million by weight.

[0032] Embodiment 10.05 is the pharmaceutical composition of embodiment 6, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 50-60 parts per million by weight.

[0033] Embodiment 10.06 is the pharmaceutical composition of embodiment 6, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 60-70 parts per million by weight.

[0034] Embodiment 10.07 is the pharmaceutical composition of embodiment 6, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 70-80 parts per million by weight.

[0035] Embodiment 10.08 is the pharmaceutical composition of embodiment 6, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 80-100 parts per million by weight.

[0036] Embodiment 10.09 is the pharmaceutical composition of any one of embodiments 1-5, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 100-200 parts per million by weight.

[0037] Embodiment 11 is the pharmaceutical composition of any one of the preceding embodiments, wherein the denatonium salt is included in a composition comprising a therapeutically effective amount of the pharmaceutical agent.

[0038] Embodiment 12 is the pharmaceutical composition of any one of the preceding embodiments, wherein the pharmaceutical composition comprises a coating.

[0039] Embodiment 13 is the pharmaceutical composition of embodiment 12, wherein the coating comprises a cellulose derivative, a vinyl polymer, or a polymethacrylate. Attorney Docket No.01309-0014-00PCT

[0040] Embodiment 14 is the pharmaceutical composition of embodiment 12 or 13, wherein the coating comprises a cellulose derivative and the cellulose derivative comprises hydroxypropyl methylcellulose, methylcellulose, or hydroxypropyl cellulose.

[0041] Embodiment 15 is the pharmaceutical composition of embodiment 12 or 13, wherein the coating comprises a vinyl polymer and the vinyl polymer comprises polyvinyl alcohol or polyvinylpyrrolidone.

[0042] Embodiment 16 is the pharmaceutical composition of embodiment 12 or 13, wherein the coating comprises a polymethacrylate and the polymethacrylate comprises a copolymer of butyl methacrylate, methacrylate, or methyl methacrylate.

[0043] Embodiment 17 is the pharmaceutical composition of any one of the preceding embodiments, wherein the coating has the property of masking the bitter taste of the denatonium salt when the pharmaceutical composition is taken or used as prescribed or is ingested whole.

[0044] Embodiment 18 is the pharmaceutical composition of any one of the preceding embodiments, wherein the coating has the property of not masking the bitter taste of the denatonium salt when the pharmaceutical composition is crushed, ground, or dissolved in a food or beverage.

[0045] Embodiment 19 is the pharmaceutical composition of any one of the preceding embodiments, wherein the pharmaceutical agent comprises an agent that causes drowsiness, an agent that depresses the central nervous system, an agent that alters consciousness, an agent that impairs decision making, an agent that lowers inhibitions, an opioid, a narcotic, a psychoactive depressant, a sedative, a hypnotic, an anxiolytic, a benzodiazepine, a non-benzodiazepine, a z- drug, an anti-psychotic, a stimulant, a hallucinogen, a euphoriant, an anti-cholinergic, an anti- histamine, or an anesthetic.

[0046] Embodiment 20 is the pharmaceutical composition of any one of embodiments 1-19, wherein the pharmaceutical composition is a solid pharmaceutical composition.

[0047] Embodiment 21 is the pharmaceutical composition of any one of embodiments 1-19, wherein the pharmaceutical composition comprises a tablet, capsule, pellet, or granule.

[0048] Embodiment 22 is the pharmaceutical composition of any one of embodiments 1-19, wherein the denatonium salt is present in the interior of the pharmaceutical composition, optionally wherein the denatonium salt is present in the interior of the tablet, capsule, pellet, or granule. Attorney Docket No.01309-0014-00PCT

[0049] Embodiment 23 is a method for reducing a risk of use of a pharmaceutical agent for drug- facilitated sexual assault or other crime, comprising use of a denatonium salt to decrease the likelihood of improper ingestion by surreptitious administration of a pharmaceutical agent.

[0050] Embodiment 24 is the method of embodiment 23, wherein the denatonium salt comprises denatonium acetate, denatonium citrate, denatonium tartrate, denatonium maleate, or denatonium saccharide.

[0051] Embodiment 25 is the method of embodiment 23 or 24, wherein the denatonium salt comprises denatonium acetate.

[0052] Embodiment 26 is the method of embodiment 23 or 24, wherein the denatonium salt comprises denatonium acetate monohydrate.

[0053] Embodiment 27 is the method of any one of embodiments 23-26, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 50 mg.

[0054] Embodiment 27.1 is the method of embodiment 27, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 5 mg.

[0055] Embodiment 27.2 is the method of embodiment 27, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 mg to about 10 mg.

[0056] Embodiment 27.3 is the method of embodiment 27, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 mg to about 20 mg.

[0057] Embodiment 27.4 is the method of embodiment 27, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20 mg to about 30 mg.

[0058] Embodiment 27.5 is the method of embodiment 27, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30 mg to about 40 mg.

[0059] Embodiment 27.6 is the method of embodiment 27, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 40 mg to about 50 mg. Attorney Docket No.01309-0014-00PCT

[0060] Embodiment 28 is the method of any one of embodiments 23-27, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 to 100 parts per million by weight or 0.01 to 0.1 milligrams per milliliter.

[0061] Embodiment 28.1 is the method of any one of Embodiments 23-27, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.05 to 1 part per million by weight.

[0062] Embodiment 28.2 is the method of Embodiment 28.1, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.1 to 1 part per million by weight.

[0063] Embodiment 28.3 is the method of Embodiment 28.1, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.1 to 0.5 part per million by weight.

[0064] Embodiment 29 is the method of Embodiment 28, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 part per million by weight.

[0065] Embodiment 30 is the method of Embodiment 28, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 2 parts per million by weight.

[0066] Embodiment 31 is the method of Embodiment 28, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 parts per million by weight.

[0067] Embodiment 32 is the method of Embodiment 28, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 parts per million by weight.

[0068] Embodiment 32.01 is the method of embodiment 28, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10-20 parts per million by weight. Attorney Docket No.01309-0014-00PCT

[0069] Embodiment 32.02 is the method of embodiment 28, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20-30 parts per million by weight.

[0070] Embodiment 32.03 is the method of embodiment 28, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30-40 parts per million by weight.

[0071] Embodiment 32.04 is the method of embodiment 28, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 40-50 parts per million by weight.

[0072] Embodiment 32.05 is the method of embodiment 28, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 50-60 parts per million by weight.

[0073] Embodiment 32.06 is the method of embodiment 28, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 60-70 parts per million by weight.

[0074] Embodiment 32.07 is the method of embodiment 28, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 70-80 parts per million by weight.

[0075] Embodiment 32.08 is the method of embodiment 28, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 80-100 parts per million by weight.

[0076] Embodiment 32.09 is the method of any one of embodiments 23-27, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 100-200 parts per million by weight.

[0077] Embodiment 33 is the method of any one of embodiments 23-32, wherein the denatonium salt is included in a composition comprising a therapeutically effective amount of the pharmaceutical agent.

[0078] Embodiment 34 is the method of any one of embodiments 23-33, wherein the denatonium salt and the pharmaceutical agent are present in a pharmaceutical composition that comprises a coating. Attorney Docket No.01309-0014-00PCT

[0079] Embodiment 35 is the method of embodiment 34, wherein the coating comprises a cellulose derivative, a vinyl polymer, or a polymethacrylate.

[0080] Embodiment 36 is the method of embodiment 34 or 35, wherein the coating comprises a cellulose derivative and the cellulose derivative comprises hydroxypropyl methylcellulose, methylcellulose, or hydroxypropyl cellulose.

[0081] Embodiment 37 is the method of embodiment 34 or 35, wherein the coating comprises a vinyl polymer and the vinyl polymer comprises polyvinyl alcohol or polyvinylpyrrolidone.

[0082] Embodiment 38 is the method of embodiment 34 or 35, wherein the coating comprises a polymethacrylate and the polymethacrylate comprises a copolymer of butyl methacrylate, methacrylate, or methyl methacrylate.

[0083] Embodiment 39 is the method of any one of embodiments 23-38, wherein the pharmaceutical agent is comprises an agent that causes drowsiness, an agent that depresses the central nervous system, an agent that alters consciousness, an agent that impairs decision making, an agent that lowers inhibitions, an opioid, a narcotic, a psychoactive depressant, a sedative, a hypnotic, an anxiolytic, a benzodiazepine, a non-benzodiazepine, a z-drug, an anti- psychotic, a stimulant, a hallucinogen, a euphoriant, an anti-cholinergic, an anti-histamine, or an anesthetic.

[0084] Embodiment 40 is a method for reducing a risk of drug abuse, comprising use of a denatonium salt to decrease the likelihood of ingestion of a pharmaceutical agent when dissolved or suspended in a liquid.

[0085] Embodiment 41 is the method of embodiment 40, wherein the ingestion of the drug is unintentional.

[0086] Embodiment 42 is the method of embodiment 40, wherein the denatonium salt comprises denatonium acetate, denatonium citrate, denatonium tartrate, denatonium maleate, or denatonium saccharide.

[0087] Embodiment 43 is the method of embodiment 40 or 42, wherein the denatonium salt comprises denatonium acetate.

[0088] Embodiment 44 is the method of embodiment 40 or 42, wherein the denatonium salt comprises denatonium acetate monohydrate. Attorney Docket No.01309-0014-00PCT

[0089] Embodiment 45 is the method of any one of embodiments 40-44, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 50 mg.

[0090] Embodiment 45.1 is the method of embodiment 45, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 5 mg.

[0091] Embodiment 45.2 is the method of embodiment 45, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 mg to about 10 mg.

[0092] Embodiment 45.3 is the method of embodiment 45, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 mg to about 20 mg.

[0093] Embodiment 45.4 is the method of embodiment 45, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20 mg to about 30 mg.

[0094] Embodiment 45.5 is the method of embodiment 45, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30 mg to about 40 mg.

[0095] Embodiment 45.6 is the method of embodiment 45, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 40 mg to about 50 mg.

[0096] Embodiment 46 is the method of any one of embodiments 40-45, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 to 100 parts per million by weight or 0.01 to 0.1 milligrams per milliliter.

[0097] Embodiment 46.1 is the pharmaceutical composition of any one of Embodiments 40-44, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.05 to 1 part per million by weight.

[0098] Embodiment 46.2 is the pharmaceutical composition of Embodiment 46.1, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the Attorney Docket No.01309-0014-00PCT denatonium salt is present in said composition in a dose of about 0.1 to 1 part per million by weight.

[0099] Embodiment 46.3 is the pharmaceutical composition of Embodiment 46.1, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.1 to 0.5 part per million by weight.

[0100] Embodiment 47 is the method of Embodiment 46, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 part per million by weight.

[0101] Embodiment 48 is the method of Embodiment 46, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 2 parts per million by weight.

[0102] Embodiment 49 is the method of Embodiment 46, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 parts per million by weight.

[0103] Embodiment 50 is the method of Embodiment 46, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 parts per million by weight.

[0104] Embodiment 50.01 is the method of embodiment 46, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10-20 parts per million by weight.

[0105] Embodiment 50.02 is the method of embodiment 46, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20-30 parts per million by weight.

[0106] Embodiment 50.03 is the method of embodiment 46, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30-40 parts per million by weight.

[0107] Embodiment 50.04 is the method of embodiment 46, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 40-50 parts per million by weight. Attorney Docket No.01309-0014-00PCT

[0108] Embodiment 50.05 is the method of embodiment 46, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 50-60 parts per million by weight.

[0109] Embodiment 50.06 is the method of embodiment 46, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 60-70 parts per million by weight.

[0110] Embodiment 50.07 is the method of embodiment 46, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 70-80 parts per million by weight.

[0111] Embodiment 50.08 is the method of embodiment 46, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 80-100 parts per million by weight.

[0112] Embodiment 50.09 is the method of any one of embodiments 40-45, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 100-200 parts per million by weight.

[0113] Embodiment 51 is the method of any one of embodiments 40-50, wherein the denatonium salt is included in a composition comprising a therapeutically effective amount of the pharmaceutical agent.

[0114] Embodiment 52 is the method of any one of embodiments 40-51, wherein the denatonium salt and the pharmaceutical agent are present in a pharmaceutical composition that comprises a coating.

[0115] Embodiment 53 is the method of embodiment 52, wherein the coating comprises a cellulose derivative, a vinyl polymer, or a polymethacrylate.

[0116] Embodiment 54 is the method of embodiment 52 or 53, wherein the coating comprises a cellulose derivative and the cellulose derivative comprises hydroxypropyl methylcellulose, methylcellulose, or hydroxypropyl cellulose.

[0117] Embodiment 55 is the method of embodiment 52 or 53, wherein the coating comprises a vinyl polymer and the vinyl polymer comprises polyvinyl alcohol or polyvinylpyrrolidone. Attorney Docket No.01309-0014-00PCT

[0118] Embodiment 56 is the method of embodiment 52 or 53, wherein the coating comprises a polymethacrylate and the polymethacrylate comprises a copolymer of butyl methacrylate, methacrylate, or methyl methacrylate.

[0119] Embodiment 57 is the method of any one of embodiments 40-56, wherein the pharmaceutical agent comprises an agent that causes drowsiness, an agent that depresses the central nervous system, an agent that alters consciousness, an agent that impairs decision making, an agent that lowers inhibitions, an opioid, a narcotic, a psychoactive depressant, a sedative, a hypnotic, an anxiolytic, a benzodiazepine, a non-benzodiazepine, a z-drug, an anti- psychotic, a stimulant, a hallucinogen, a euphoriant, an anti-cholinergic, an anti-histamine, or an anesthetic.

[0120] Embodiment 58 is a method for making the taste of a pharmaceutical agent less palatable when improperly ingested, comprising adding a subclinical dose of a denatonium salt to a pharmaceutical composition.

[0121] Embodiment 59 is the method of embodiment 58, wherein the denatonium salt comprises denatonium acetate, denatonium citrate, denatonium tartrate, denatonium maleate, or denatonium saccharide.

[0122] Embodiment 60 is the method of embodiment 58 or 59, wherein the denatonium salt comprises denatonium acetate.

[0123] Embodiment 61 is the method of embodiment 58 or 59, wherein the denatonium salt comprises denatonium acetate monohydrate.

[0124] Embodiment 62 is the method of any one of embodiments 58-61, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 50 mg.

[0125] Embodiment 62.1 is the method embodiment 62, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 5 mg.

[0126] Embodiment 62.2 is the method of embodiment 62, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 mg to about 10 mg. Attorney Docket No.01309-0014-00PCT

[0127] Embodiment 62.3 is the method of embodiment 62, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 mg to about 20 mg.

[0128] Embodiment 62.4 is the method of embodiment 62, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20 mg to about 30 mg.

[0129] Embodiment 62.5 is the method of embodiment 62, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30 mg to about 40 mg.

[0130] Embodiment 62.6 is the method of embodiment 62, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 40 mg to about 50 mg.

[0131] Embodiment 63 is the method of any one of embodiments 58-62, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 to 100 parts per million by weight or 0.01 to 0.1 milligrams per milliliter.

[0132] Embodiment 63.1 is the pharmaceutical composition of Embodiment 63, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.05 to 1 part per million by weight.

[0133] Embodiment 63.2 is the pharmaceutical composition of Embodiment 63, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.1 to 1 part per million by weight.

[0134] Embodiment 63.3 is the pharmaceutical composition of Embodiment 63, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.1 to 0.5 part per million by weight.

[0135] Embodiment 64 is the method of embodiment 63, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 part per million by weight. Attorney Docket No.01309-0014-00PCT

[0136] Embodiment 65 is the method of embodiment 63, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 2 parts per million by weight.

[0137] Embodiment 66 is the method of embodiment 63, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 parts per million by weight.

[0138] Embodiment 67 is the method of embodiment 63, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 parts per million by weight.

[0139] Embodiment 67.01 is the method of embodiment 63, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10-20 parts per million by weight.

[0140] Embodiment 67.02 is the method of embodiment 63, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20-30 parts per million by weight.

[0141] Embodiment 67.03 is the method of embodiment 63, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30-40 parts per million by weight.

[0142] Embodiment 67.04 is the method of embodiment 63, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 40-50 parts per million by weight.

[0143] Embodiment 67.05 is the method of embodiment 63, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 50-60 parts per million by weight.

[0144] Embodiment 67.06 is the method of embodiment 63, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 60-70 parts per million by weight.

[0145] Embodiment 67.07 is the method of embodiment 63, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 70-80 parts per million by weight. Attorney Docket No.01309-0014-00PCT

[0146] Embodiment 67.08 is the method of embodiment 63, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 80-100 parts per million by weight.

[0147] Embodiment 67.09 is the method of any one of embodiments 58-62, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 100-200 parts per million by weight.

[0148] Embodiment 68 is the method of any one of embodiments 58-67, wherein the denatonium salt is included in a composition comprising a therapeutically effective amount of the pharmaceutical agent.

[0149] Embodiment 69 is the method of any one of embodiments 58-68, wherein the pharmaceutical composition comprises a coating.

[0150] Embodiment 70 is the method of any one of embodiments 58-69, wherein the pharmaceutical agent comprises an agent that causes drowsiness, an agent that depresses the central nervous system, an agent that alters consciousness, an agent that impairs decision making, an agent that lowers inhibitions, an opioid, a narcotic, a psychoactive depressant, a sedative, a hypnotic, an anxiolytic, a benzodiazepine, a non-benzodiazepine, a z-drug, an anti- psychotic, a stimulant, a hallucinogen, a euphoriant, an anti-cholinergic, an anti-histamine, or an anesthetic.

[0151] Embodiment 71 is a method for making the taste of a pharmaceutical agent less palatable when dissolved or suspended in a liquid, comprising adding a subclinical dose of a denatonium salt to a pharmaceutical composition.

[0152] Embodiment 72 is the method of embodiment 71, wherein the denatonium salt comprises denatonium acetate, denatonium citrate, denatonium tartrate, denatonium maleate, or denatonium saccharide.

[0153] Embodiment 73 is the method of embodiment 71 or 72, wherein the denatonium salt comprises denatonium acetate.

[0154] Embodiment 74 is the method of embodiment 71 or 72, wherein the denatonium salt comprises denatonium acetate monohydrate. Attorney Docket No.01309-0014-00PCT

[0155] Embodiment 75 is the method of any one of embodiments 71-74, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 50 mg.

[0156] Embodiment 75.1 is the method of embodiment 75, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 5 mg.

[0157] Embodiment 75.2 is the method of embodiment 75, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 mg to about 10 mg.

[0158] Embodiment 75.3 is the method of embodiment 75, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 mg to about 20 mg.

[0159] Embodiment 75.4 is the method of embodiment 75, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20 mg to about 30 mg.

[0160] Embodiment 75.5 is the method of embodiment 75, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30 mg to about 40 mg.

[0161] Embodiment 75.6 is the method of embodiment 75, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 40 mg to about 50 mg.

[0162] Embodiment 76 is the method of any one of embodiments 71-75, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 to 100 parts per million by weight or 0.01 to 0.1 milligrams per milliliter.

[0163] Embodiment 76.1 is the pharmaceutical composition of any one of Embodiments 71-75, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.05 to 1 part per million by weight.

[0164] Embodiment 76.2 is the pharmaceutical composition of Embodiment 76.1, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the Attorney Docket No.01309-0014-00PCT denatonium salt is present in said composition in a dose of about 0.1 to 1 part per million by weight.

[0165] Embodiment 76.3 is the pharmaceutical composition of Embodiment 76.1, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.1 to 0.5 part per million by weight.

[0166] Embodiment 77 is the method of Embodiment 76, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 part per million by weight.

[0167] Embodiment 78 is the method of Embodiment 76, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 2 parts per million by weight.

[0168] Embodiment 79 is the method of Embodiment 76, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 parts per million by weight.

[0169] Embodiment 80 is the method of Embodiment 76, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 parts per million by weight.

[0170] Embodiment 80.01 is the method of embodiment 76, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10-20 parts per million by weight.

[0171] Embodiment 80.02 is the method of embodiment 76, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20-30 parts per million by weight.

[0172] Embodiment 80.03 is the method of embodiment 76, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30-40 parts per million by weight.

[0173] Embodiment 80.04 is the method of embodiment 76, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 40-50 parts per million by weight. Attorney Docket No.01309-0014-00PCT

[0174] Embodiment 80.05 is the method of embodiment 76, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 50-60 parts per million by weight.

[0175] Embodiment 80.06 is the method of embodiment 76, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 60-70 parts per million by weight.

[0176] Embodiment 80.07 is the method of embodiment 76, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 70-80 parts per million by weight.

[0177] Embodiment 80.08 is the method of embodiment 76, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 80-100 parts per million by weight.

[0178] Embodiment 80.09 is the method of any one of embodiments 71-75, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 100-200 parts per million by weight.

[0179] Embodiment 81 is the method of any one of embodiments 71-80, wherein the denatonium salt is included in a composition comprising a therapeutically effective amount of the pharmaceutical agent.

[0180] Embodiment 82 is the method of any one of embodiments 71-81, wherein the pharmaceutical composition comprises a coating.

[0181] Embodiment 83 is the method of any one of embodiments 71-82, wherein the pharmaceutical agent comprises an agent that causes drowsiness, an agent that depresses the central nervous system, an agent that alters consciousness, an agent that impairs decision making, an agent that lowers inhibitions, an opioid, a narcotic, a psychoactive depressant, a sedative, a hypnotic, an anxiolytic, a benzodiazepine, a non-benzodiazepine, a z-drug, an anti- psychotic, a stimulant, a hallucinogen, a euphoriant, an anti-cholinergic, an anti-histamine, or an anesthetic.

[0182] Embodiment 84 is a method for making a pharmaceutical composition detectable when dissolved or suspended in a liquid, comprising adding a subclinical dose of a denatonium salt to Attorney Docket No.01309-0014-00PCT a pharmaceutical composition that includes a pharmaceutical agent such that when dissolved in a liquid, the taste of the liquid becomes bitter.

[0183] Embodiment 85 is the method of embodiment 84, wherein the denatonium salt comprises denatonium acetate, denatonium citrate, denatonium tartrate, denatonium maleate, or denatonium saccharide.

[0184] Embodiment 86 is the method of embodiment 84 or 85, wherein the denatonium salt comprises denatonium acetate.

[0185] Embodiment 87 is the method of embodiment 84 or 85, wherein the denatonium salt comprises denatonium acetate monohydrate.

[0186] Embodiment 88 is the method of any one of embodiments 84-87, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 50 mg.

[0187] Embodiment 88.1 is the method of embodiment 88, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 5 mg.

[0188] Embodiment 88.2 is the method of embodiment 88, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 mg to about 10 mg.

[0189] Embodiment 88.3 is the method of embodiment 88, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 mg to about 20 mg.

[0190] Embodiment 8.4 is the method of embodiment 88, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20 mg to about 30 mg.

[0191] Embodiment 8.5 is the method of embodiment 88, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30 mg to about 40 mg.

[0192] Embodiment 8.6 is the method of embodiment 88, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 40 mg to about 50 mg. Attorney Docket No.01309-0014-00PCT

[0193] Embodiment 89 is the method of any one of embodiments 84-88, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 to 100 parts per million by weight or 0.01 to 0.1 milligrams per milliliter.

[0194] Embodiment 89.1 is the pharmaceutical composition of any one of Embodiments 84-88, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.05 to 1 part per million by weight.

[0195] Embodiment 89.2 is the pharmaceutical composition of Embodiment 89.1, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.1 to 1 part per million by weight.

[0196] Embodiment 89.3 is the pharmaceutical composition of Embodiment 89.1, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.1 to 0.5 part per million by weight.

[0197] Embodiment 90 is the method of Embodiment 89, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 part per million by weight.

[0198] Embodiment 91 is the method of Embodiment 89, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 2 parts per million by weight.

[0199] Embodiment 92 is the method of Embodiment 89, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 parts per million by weight.

[0200] Embodiment 93 is the method of Embodiment 89, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 parts per million by weight.

[0201] Embodiment 93.01 is the method of embodiment 89, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10-20 parts per million by weight. Attorney Docket No.01309-0014-00PCT

[0202] Embodiment 93.02 is the method of embodiment 89, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20-30 parts per million by weight.

[0203] Embodiment 93.03 is the method of embodiment 89, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30-40 parts per million by weight.

[0204] Embodiment 93.04 is the method of embodiment 89, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 40-50 parts per million by weight.

[0205] Embodiment 93.05 is the method of embodiment 89, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 50-60 parts per million by weight.

[0206] Embodiment 93.06 is the method of embodiment 89, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 60-70 parts per million by weight.

[0207] Embodiment 93.07 is the method of embodiment 89, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 70-80 parts per million by weight.

[0208] Embodiment 93.08 is the method of embodiment 89, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 80-100 parts per million by weight.

[0209] Embodiment 93.09 is the method of any one of embodiments 84-88, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 100-200 parts per million by weight.

[0210] Embodiment 94 is the method of any one of embodiments 84-93, wherein the denatonium salt is included in a composition comprising a therapeutically effective amount of the pharmaceutical agent.

[0211] Embodiment 95 is the method of any one of embodiments 84-94, wherein the pharmaceutical composition comprises a coating. Attorney Docket No.01309-0014-00PCT

[0212] Embodiment 96 is the method of any one of embodiments 84-95, wherein the pharmaceutical agent comprises an agent that causes drowsiness, an agent that depresses the central nervous system, an agent that alters consciousness, an agent that impairs decision making, an agent that lowers inhibitions, an opioid, a narcotic, a psychoactive depressant, a sedative, a hypnotic, an anxiolytic, a benzodiazepine, a non-benzodiazepine, a z-drug, an anti- psychotic, a stimulant, a hallucinogen, a euphoriant, an anti-cholinergic, an anti-histamine, or an anesthetic.

[0213] Embodiment 97 is a method of making a date rape drug ineffective for drug-facilitated sexual assault, comprising including a denatonium salt in a pharmaceutical composition comprising the date rape drug.

[0214] Embodiment 98 is the method of embodiment 97, wherein the denatonium salt comprises denatonium acetate, denatonium citrate, denatonium tartrate, denatonium maleate, or denatonium saccharide.

[0215] Embodiment 99 is the method of embodiment 97 or 98, wherein the denatonium salt comprises denatonium acetate.

[0216] Embodiment 100 is the method of embodiment 97 or 98, wherein the denatonium salt comprises denatonium acetate monohydrate.

[0217] Embodiment 101 is the method of any one of embodiments 97-100, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 50 mg.

[0218] Embodiment 101.1 is the method of embodiment 101, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 5 mg.

[0219] Embodiment 101.2 is the method of embodiment 101, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 mg to about 10 mg.

[0220] Embodiment 101.3 is the method of embodiment 101, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 mg to about 20 mg. Attorney Docket No.01309-0014-00PCT

[0221] Embodiment 101.4 is the method of embodiment 101, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20 mg to about 30 mg.

[0222] Embodiment 101.5 is the method of embodiment 101, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30 mg to about 40 mg.

[0223] Embodiment 101.6 is the method of embodiment 101, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 40 mg to about 50 mg.

[0224] Embodiment 102 is the method of any one of embodiments 97-101, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 to 100 parts per million by weight or 0.01 to 0.1 milligrams per milliliter.

[0225] Embodiment 102.1 is the pharmaceutical composition of any one of Embodiments 97- 101, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.05 to 1 part per million by weight.

[0226] Embodiment 102.2 is the pharmaceutical composition of Embodiment 102.1, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.1 to 1 part per million by weight.

[0227] Embodiment 102.3 is the pharmaceutical composition of Embodiment 102.1, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.1 to 0.5 part per million by weight.

[0228] Embodiment 103 is the method of Embodiment 102, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 part per million by weight.

[0229] Embodiment 104 is the method of Embodiment 102, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 2 parts per million by weight. Attorney Docket No.01309-0014-00PCT

[0230] Embodiment 105 is the method of Embodiment 102, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 parts per million by weight.

[0231] Embodiment 106 is the method of Embodiment 102, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 parts per million by weight.

[0232] Embodiment 106.01 is the method of embodiment 102, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10-20 parts per million by weight.

[0233] Embodiment 106.02 is the method of embodiment 102, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20-30 parts per million by weight.

[0234] Embodiment 106.03 is the method of embodiment 102, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30-40 parts per million by weight.

[0235] Embodiment 106.04 is the method of embodiment 102, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 40-50 parts per million by weight.

[0236] Embodiment 106.05 is the method of embodiment 102, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 50-60 parts per million by weight.

[0237] Embodiment 106.06 is the method of embodiment 102, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 60-70 parts per million by weight.

[0238] Embodiment 106.07 is the method of embodiment 102, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 70-80 parts per million by weight.

[0239] Embodiment 106.08 is the method of embodiment 102, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 80-100 parts per million by weight. Attorney Docket No.01309-0014-00PCT

[0240] Embodiment 106.09 is the method of any one of embodiments 97-101, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 100-200 parts per million by weight.

[0241] Embodiment 107 is the method of any one of embodiments 97-106, wherein a therapeutically effective amount of the date rape drug is provided.

[0242] Embodiment 108 is the method of any one of embodiments 97-107, wherein the date rape drug is present in a pharmaceutical composition that comprises a coating.

[0243] Embodiment 109 is the method of embodiment 108, wherein the coating comprises a cellulose derivative, a vinyl polymer, or a polymethacrylate.

[0244] Embodiment 110 is the method of embodiment 108 or 109, wherein the coating comprises a cellulose derivative and the cellulose derivative comprises hydroxypropyl methylcellulose, methylcellulose, or hydroxypropyl cellulose.

[0245] Embodiment 111 is the method of embodiment 108 or 109, wherein the coating comprises a vinyl polymer and the vinyl polymer comprises polyvinyl alcohol or polyvinylpyrrolidone.

[0246] Embodiment 112 is the method of embodiment 108 or 109, wherein the coating comprises a polymethacrylate and the polymethacrylate comprises a copolymer of butyl methacrylate, methacrylate, or methyl methacrylate

[0247] Embodiment 113 is the method of any one of embodiments 97-112, wherein the date rape drug is ingested unintentionally by a subject.

[0248] Embodiment 114 is the method of any one of embodiments 97-113, wherein the date rape drug causes an effect in a subject.

[0249] Embodiment 115 is the method of embodiment 114, wherein the effect comprises impaired judgment, or sedation.

[0250] Embodiment 116 is the method of embodiment 114 or 115, wherein the effect makes a subject more vulnerable to sexual assault.

[0251] Embodiment 117 is the pharmaceutical composition of any one of embodiments 23-116, wherein the pharmaceutical composition is a solid pharmaceutical composition.

[0252] Embodiment 118 is the pharmaceutical composition of any one of embodiments 23-117, wherein the pharmaceutical composition comprises a tablet, capsule, pellet, or granule. Attorney Docket No.01309-0014-00PCT

[0253] Embodiment 119 is the pharmaceutical composition of any one of embodiments 23-118, wherein the denatonium salt is present in the interior of the pharmaceutical composition, optionally wherein the denatonium salt is present in the interior of the tablet, capsule, pellet, or granule. DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS

[0254] Reference will now be made in detail to certain embodiments of the invention. While the invention will be described in conjunction with such embodiments, it will be understood that they are not intended to limit the invention to those embodiments. On the contrary, the invention is intended to cover all alternatives, modifications, and equivalents, which may be included within the invention as defined by the appended claims.

[0255] Before describing the present teachings in detail, it is to be understood that the disclosure is not limited to specific compositions or process steps, as such may vary. It should be noted that, as used in this specification and the appended claims, the singular form “a”, “an” and “the” include plural references unless the context clearly dictates otherwise. Thus, for example, reference to “an emulsifier” includes a plurality of emulsifiers, and the like. “Or” is used in the inclusive sense, equivalent to “and / or”, unless the context clearly dictates otherwise.

[0256] Numeric ranges are inclusive of the numbers defining the range. Measured and measurable values are understood to be approximate, taking into account significant digits and the error associated with the measurement. Also, the use of “comprise”, “comprises”, “comprising”, “contain”, “contains”, “containing”, “include”, “includes”, and “including” are not intended to be limiting. It is to be understood that both the foregoing general description and detailed description are exemplary and explanatory only and are not restrictive of the teachings.

[0257] Unless specifically noted in the specification, embodiments in the specification that recite “comprising” various components are also contemplated as “consisting of” or “consisting essentially of” the recited components; embodiments in the specification that recite “consisting of” various components are also contemplated as “comprising” or “consisting essentially of” the recited components; and embodiments in the specification that recite “consisting essentially of” various components are also contemplated as “consisting of” or “comprising” the recited components (this interchangeability does not apply to the use of these terms in the claims). Any Attorney Docket No.01309-0014-00PCT “pharmaceutical composition” described herein is also contemplated as a "composition” or “formulation.”

[0258] The section headings used herein are for organizational purposes and are not to be construed as limiting the disclosed subject matter in any way. In the event that any document or other material incorporated by reference contradicts any explicit content of this specification, including definitions, this specification controls. I. Definitions

[0259] Unless defined otherwise, all technical and scientific terms have the same meaning and is commonly understood by one of ordinary skill in the art to which the embodiments disclosed belongs. In the even that there is a plurality of definitions for terms cited herein, those in this section prevail unless otherwise stated. All patents, applications, published applications, and other publications cited herein are incorporated by reference in their entirety.

[0260] The terms “a” or “an” as used herein refers to “at least one” or “one or more” unless the context clearly indicates otherwise.

[0261] The term “or” as used herein is used in the inclusive sense (equivalent to “and / or”) unless the context requires otherwise.

[0262] Ranges and amounts as used herein can be expressed as “about” a particular value or range. About also includes the exact amount. Hence “about 5 mg” refers to “about 5 mg” and also “5 mg.” Generally, the term “about” includes an amount that would be expected to be within experimental error, such as for example, within 15%, 10%, or 5%.

[0263] The terms “composition” and “formulation” as used herein may be used interchangeably and refer to a combination of elements that is presented together for a given purpose. Such terms are well known to those of ordinary skill in the art. “Formulations” also refers to a composition comprising at least one compound as disclosed herein formulated together with one or more pharmaceutically acceptable carriers, excipients, or diluents. Non-limiting examples of compositions include, but are not limited to tablets, capsules, pellets, granules, oral liquids, parenteral, cutaneous, creams, ointments, gels, pastes, powders, sprays, lotions, foams, subcutaneous, suppositories, and coatings, and may vary in the manner in which the active pharmaceutical ingredient is released, e.g., have an immediate-release or extended-release profile. Attorney Docket No.01309-0014-00PCT

[0264] The term “pharmaceutical agent” as used herein is interchangeable with “drug” and refers to any pharmaceutically active substance in a pharmaceutical composition. Exemplary pharmaceutical agents include, but are not limited to, agents used for drug-facilitated sexual assault or other crime an agent that causes drowsiness; agents that depress the central nervous system; agents that alter consciousness; agents that impair decision making; agents that lower inhibitions; opioids; narcotics; psychoactive depressants; sedatives; hypnotics; anxiolytics; the benzodiazepine or non-benzodiazepine classes; z-drugs; anti-psychotics; stimulants; hallucinogens; euphoriants; anti-cholinergics; anti-histamines; or anesthetics.

[0265] The terms “comprising” (and any form of comprising, such as “comprise”, “comprises”, and “comprised”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”), or “containing” (and any form of containing, such as “contains” and “contain”) as used herein are inclusive or open-ended and do not exclude additional, unrecited elements, or method steps.

[0266] The term “date rape drug” as used herein refers to a drug that acts as a nervous system depressant, which can produce feelings of euphoria, relaxation, or sociability. Further, a “date rape drug” refers to any drug that incapacitates another person or renders that person vulnerable to sexual assault, including rape. Examples of date rape drugs include, but are not limited to, gamma-hydroxybutyrate (also known as “GHB”), flunitrazepam (i.e., Rohypnol), ketamine, alcohol, 4-hydroxybutanoic acid, 4-hydroxypentanoic acid, zolpidem, benzodiazepine drugs (such as Valium, Xanax, Halcion, Ativan, or Klonopin), non-benzodiazepine hypnotics, opioids, scopolamine, anticholinergic drugs (such as Benadryl, Tylenol PM, Advil PM, Unisom SleepGels, Dimetapp, Dramamine, or Unisom SleepTabs), and diazepam..

[0267] The term “z-drug” as used herein refers to the non-benzodiazepine class of hypnotics. Examples of z-drugs include Eszopiclone (also known as Lunesta), Zaleplon (also known as Sonata), and Zolpidem (also known as Ambien, Ambien CR, Edluar, Zolpimist).

[0268] The term “agents that cause drowsiness” as used herein refers to agents that cause sleepiness in a subject. Common agents that cause drowsiness include, but are not limited to, allergy medications, antidepressants, anxiety medications, blood pressure medications, cancer treatment, gut medications, muscle relaxants, opioid pain medications, and seizure or epilepsy medications. Attorney Docket No.01309-0014-00PCT

[0269] The term “agents that depress the central nervous system” as used herein refers to drugs that slow down brain activity and can cause muscles to relax, also known as sedatives or tranquilizers.

[0270] The term “narcotics” as used herein refers to any psychoactive compound with numbing or paralyzing properties. Narcotics include, but are not limited to, opiates and opioids, commonly opium, morphine, and heroin, as well as derivatives of many of the compounds found within raw opium latex. The term “narcotics” also refers to a variety of substances that dull the senses and relieve pain. Examples include, but are not limited to, the illicit drug heroin and prescription drugs like OxyContin, Vicodin, codeine, morphine, methadone, and fentanyl.

[0271] The term “therapeutically effective amount” as used herein refers to an amount sufficient to provide a therapeutic benefit (e.g., treating, preventing, and / or ameliorating an indication in a subject, or inhibiting protein-protein interactions in a subject, at a reasonable benefit / risk ratio applicable to any medical treatment) in the treatment of a disease, disorder, or conditions, or to delay or minimize one or more symptoms associated with the disease, disorder, or condition. A therapeutically effective amount of a compound means an amount of therapeutic agent, alone or in combination with other therapies, which provides a therapeutic benefit in the treatment of the disease, disorder, or condition. The term “therapeutically effective amount” can encompass an amount that improves overall therapy, reduces or avoids symptoms or causes of disease or condition, or enhances the therapeutic efficacy of another therapeutic agent.

[0272] The term “subclinical dose” as used herein refers to a dose that is not detectable or producing effects that are not detectable by the usual clinical tests.

[0273] The term “less palatable” as used herein refers to something that is made less agreeable, less pleasant, less tolerable, or less edible for ingestion.

[0274] The term “improper ingestion” as used herein refers to any unwanted, unsolicited, or non- prescribed ingestion. Improper ingestion can include poisoning. Poisoning can be intentional (on purpose) or unintentional (accidental). Poison exposure can be acute (a single event, short-term) or chronic (longer-term).

[0275] The term “coating” refers to a substance added to an oral dosage form that can impact both its appearance and its pharmacokinetics making it an important process in making the final pharmaceutical composition. Types of coatings include, but are not limited to, film coatings, non-functional coatings, functional coatings, organic solvent-based coatings, aqueous coatings, Attorney Docket No.01309-0014-00PCT and solvent-free coatings. A film coating is a thin polymer-based coat that is typically sprayed onto solid pharmaceutical dosage forms, such as tablets, capsules, pellets, or granules. A non- functional coating involves changes made to the aesthetic of the oral dosage form. Such changes affect an oral dosage form's appearance, organoleptic properties, swallowing properties, or provide protection against harsh environmental conditions that can damage the active pharmaceutical ingredient. These changes are conducted to improve the compliance and effects of the oral dosage form. A functional film coating provides the same properties as non-functional film coating, but also has added properties that affect drug release. These changes alter the region in the gastrointestinal tract where the final pharmaceutical composition is released. An organic solvent-based coating is typically used to incorporate protective coatings to the oral dosage form, which aids in increasing the shelf life of the final pharmaceutical composition. An aqueous film coating uses water to aid in the film coating process instead of organic solvents. A solvent-free coating is most commonly used in coating heat sensitive drugs due to the benefit of not requiring a drying phase. The end result of this type of film coating is an inert film coating that does not react with the active pharmaceutical ingredients. Some methods to create a solvent- free film coating include, but are not limited to, injection molding coating, hot-melt coating, and spray congealing.

[0276] Examples of film coatings include, but are not limited to, cellulose derivatives (such as hydroxypropyl methylcellulose, methylcellulose, hydroxypropyl cellulose), vinyl polymers (such as polyvinyl alcohol, polyvinylpyrrolidone), polymethacrylates (such as copolymers of butyl methacrylate, methacrylate, methyl methacrylate), other polymers (such as modified starches, polysaccharides), or any additional film coating formula constructed from polymers, plasticizers, surfactants or other appropriate additives that serve purposes including pharmaceutical composition protection, masking of taste of odors, improving mechanical strength, or facilitating product handling.

[0277] The term “anterograde amnesia” refers to the inability to form new memories.

[0278] Section headings are provided solely for the convenience of the reader and do not limit the disclosure. II. Pharmaceutical Formulations

[0279] Provided herein is a pharmaceutical composition comprising a denatonium salt and a pharmaceutical agent, wherein the pharmaceutical agent is used, or is capable of being used, for Attorney Docket No.01309-0014-00PCT drug-facilitated sexual assault or other crime and / or comprises an agent that causes drowsiness, an agent that depresses the central nervous system, an agent that alters consciousness, an agent that impairs decision making, an agent that lowers inhibitions, an opioid, a narcotic, a psychoactive depressant, a sedative, a hypnotic, an anxiolytic, a benzodiazepine, a non- benzodiazepine, a z-drug, an anti-psychotic, a stimulant, a hallucinogen, a euphoriant, an anti- cholinergic, an anti-histamine, or an anesthetic. A. Denatonium Salts

[0280] Denatonium, e.g., as denatonium benzoate (under trade names such as Denatrol, BITTERANT-b, BITTER+PLUS, Bitrex, Bitrix, or Aversion) and as denatonium saccharide (BITTERANT-s), is an extremely bitter chemical compound, with bitterness thresholds of 0.05 ppm for the benzoate and 0.01 ppm for the saccharide. Denatonium salts are usually colorless and odorless solids but are often in solution. Denatonium is recognized by eight distinct bitter taste receptors in humans: TAS2R4, TAS2R8, TAS2R10, TAS2R39, TAS2R43, TAS2R16, TAS2R46, and TAS2R47.

[0281] Denatonium salts are the most bitter tastants among tens of thousands of natural or synthesized bitter compounds, with a bitterness detection threshold of 0.05 parts per million (ppm). Bitter taste receptors (TAS2Rs) are expressed in various tissues and organs including the mouth, nasal cavity, gastrointestinal (GI) tract, pancreas, adipose tissue, lung, trachea, skin, and central nervous system (CNS). Beyond their role in taste perception, these receptors are involved in multiple physiological functions, including the regulation of metabolic and inflammatory processes, highlighting their importance in overall human physiology. Upon release in the gut, the drug binds to TAS2Rs and stimulates enteroendocrine cells to release multiple peptide hormones involved in hunger control, acting in an autocrine / paracrine manner to regulate hunger, metabolism, and inflammation.

[0282] Upon contact with the tissues in the mouth, denatonium acetate monohydrate immediately induces an extremely aversive bitter taste. This has been found to be useful in the context of a method of reducing the risk of drug abuse, drug-facilitated sexual assault (i.e., date rape), and / or other crime, and to decrease the likelihood of improper ingestion of a pharmaceutical agent by, e.g., making the taste of a pharmaceutical agent detectable and / or less palatable or alerting an unsuspecting recipient that the drink has been adulterated. Attorney Docket No.01309-0014-00PCT

[0283] Denatonium acetate monohydrate (DAM) has been shown to have beneficial therapeutic effects. Specifically, denatonium acetate monohydrate is shown to be gut restricted (>99%) with minimal systemic exposure (~1%), thus avoiding off-target toxicities, an attribute highly desirable in the development of safe drugs suitable for chronic treatment (Niethammer, et al., Clin Pharmacol Drug Dev, 2022, 11(8), pages 997-1006). It is also not known to pose any long- term health risks.

[0284] Denatonium is a quaternary ammonium cation. It is generally provided as a salt with any of several anions, such as benzoate or saccharinate. It can be obtained by the quaternization of lidocaine, a popular anesthetic, with benzyl chloride or a similar reagent. To obtain other salts, like the benzoate, the formed denatonium chloride is subjected to an anion exchange reaction with sodium benzoate, or first sodium hydroxide to make denatonium hydroxide followed by neutralization with benzoic acid.

[0285] Denatonium acetate monohydrate (DAM) may be prepared by a process comprising the steps of contacting an equivalent of DAA (denatonium acetate, anhydrous) with a lower alkyl isobutyl ketone, such as methyl isobutyl ketone, and water such that the water concentration is above 10 weight percent, recovering the resultant solid phase, and removing the solid therefrom. Step 1: Synthesis of Denatonium Hydroxide from Lidocaine

[0286] To a reflux apparatus, 25 g of lidocaine, 60 ml of water, and 17.5 g of benzyl chloride are added, with stirring and heating in 70-90 °C. The solution is heated and stirred in the before given value for 24h, then cooled down to 30 °C. The unreacted reagents are removed with 3×10 mL of toluene. With stirring, 65 g of sodium hydroxide is added into 65 mL of cold water and then added to the aqueous solution with stirring over the course of 3 h. The mixture is filtered, washed with some water, and dried in open air. The mixture is then recrystallized in hot chloroform or hot ethanol. Step 2: Preparation of Denatonium Acetate, anhydrous (DAA) from Denatonium Hydroxide

[0287] To a reflux apparatus, 10 g of denatonium hydroxide (MW: 342.475 g / mol, 0.029 mol), 20 mL of acetone, and 2 g of acetic acid glacial (0.033 mol) dissolved in 15 mL of acetone is added, the mixture is stirred and heated to 35 °C for 3 h, then evaporated to dryness and recrystallized in hot acetone.

[0288] DAA was maintained in an organic layer and was distilled under vacuum until the temperature reached 65-67 °C at <150 torr. Methyl isobutyl ketone was added and refluxed Attorney Docket No.01309-0014-00PCT under vacuum to remove water via azeotropic distillation to form DAM. DAM was crystalized by adding isopropyl alcohol. Residual salts were removed. The mixture was distilled under vacuum. Next, methyl isobutyl ketone was added and then water. The temperature was lowered to <10 °C. The remaining solid was isolated and washed with methyl isobutyl ketone to produce the final DAM (denatonium acetate monohydrate).

[0289] In some embodiments, the denatonium salt comprises denatonium acetate, denatonium citrate, denatonium tartrate, denatonium maleate, or denatonium saccharide. In some embodiments, the denatonium salt comprises denatonium acetate, e.g., denatonium acetate monohydrate.

[0290] In some embodiments, the denatonium salt is denatonium acetate. In some embodiments, the denatonium salt is denatonium acetate monohydrate. In some embodiments, the denatonium salt is denatonium citrate. In some embodiments, the denatonium salt is denatonium tartrate. In some embodiments, the denatonium salt is denatonium maleate. In some embodiments, the denatonium salt is denatonium saccharide. B. Pharmaceutical Composition

[0291] Provided herein is a pharmaceutical composition comprising a denatonium salt and a pharmaceutical agent, wherein the pharmaceutical agent is used, or is capable of being used, for drug-facilitated sexual assault or other crime and / or comprises an agent that causes drowsiness, an agent that depresses the central nervous system, an agent that alters consciousness, an agent that impairs decision making, an agent that lowers inhibitions, an opioid, a narcotic, a psychoactive depressant, a sedative, a hypnotic, an anxiolytic, the benzodiazepine or non- benzodiazepine class or z-drug, an anti-psychotic, a stimulant, a hallucinogen, a euphoriant, an anti-cholinergic, an anti-histamine, or an anesthetic.

[0292] A pharmaceutical composition may be present as an oral solid dosage (“OSD”) form. OSD products come in different forms including, but not limited to tablets, capsules, pellets, and granules.

[0293] In some embodiments, the denatonium salt comprises denatonium acetate, denatonium citrate, denatonium tartrate, denatonium maleate, or denatonium saccharide.

[0294] In some embodiments, the denatonium salt comprises denatonium acetate.

[0295] In some embodiments, the denatonium salt comprises denatonium acetate monohydrate. Attorney Docket No.01309-0014-00PCT

[0296] In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 50 mg.

[0297] In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 to 100 parts per million by weight. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.05 part per million by weight, about 0.1 part per million by weight, or about 0.5 parts per million by weight. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 part per million by weight, about 2 parts per million by weight, about 3 parts per million by weight, about 4 parts per million by weight, about 5 parts per million by weight, about 6 parts per million by weight, about 7 parts per million by weight, about 8 parts per million by weight, about 9 parts per million by weight, or about 10 parts per million by weight. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1-10 parts per million by weight, e.g., about 1-2 parts per million by weight, about 2-3 parts per million by weight, about 3-4 parts per million by weight, about 4- 5 parts per million by weight, about 5-6 parts per million by weight, about 6-7 parts per million by weight, about 7-8 parts per million by weight, about 8-9 parts per million by weight, or about 9-10 parts per million by weight.

[0298] In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 to 100 parts per million by weight or 0.01 to 0.1 milligrams per milliliter.

[0299] In some embodiments, the denatonium salt is included in a composition comprising a therapeutically effective amount of the pharmaceutical agent.

[0300] In some embodiments, the pharmaceutical composition comprises a coating.

[0301] In some embodiments, the coating comprises a cellulose derivative, a vinyl polymer, or a polymethacrylate.

[0302] In some embodiments, the cellulose derivative comprises hydroxypropyl methylcellulose, methylcellulose, or hydroxypropyl cellulose. Attorney Docket No.01309-0014-00PCT

[0303] In some embodiments, the vinyl polymer comprises polyvinyl alcohol or polyvinylpyrrolidone.

[0304] In some embodiments, the polymethacrylate comprises a copolymer of butyl methacrylate, methacrylate, or methyl methacrylate.

[0305] In some embodiments, the coating comprises a cellulose derivative and the cellulose derivative comprises hydroxypropyl methylcellulose, methylcellulose, or hydroxypropyl cellulose.

[0306] In some embodiments, the coating comprises a vinyl polymer and the vinyl polymer comprises polyvinyl alcohol or polyvinylpyrrolidone.

[0307] In some embodiments, the coating comprises a polymethacrylate and the polymethacrylate comprises a copolymer of butyl methacrylate, methacrylate, or methyl methacrylate.

[0308] In some embodiments, the coating has the property of masking the bitter taste of the denatonium salt when the pharmaceutical composition is taken or used as prescribed or is ingested whole.

[0309] In some embodiments, the coating has the property of not masking the bitter taste of the denatonium salt when the pharmaceutical composition is crushed, ground, or dissolved in a food or beverage.

[0310] In some embodiments, the pharmaceutical agent comprises an agent that causes drowsiness, an agent that depresses the central nervous system, an agent that alters consciousness, an agent that impairs decision making, an agent that lowers inhibitions, an opioid, a narcotic, a psychoactive depressant, a sedative, a hypnotic, an anxiolytic, a benzodiazepine, a non-benzodiazepine, a z-drug, an anti-psychotic, a stimulant, a hallucinogen, a euphoriant, an anti-cholinergic, an anti-histamine, or an anesthetic.

[0311] In some embodiments, the pharmaceutical composition is a solid pharmaceutical composition.

[0312] In some embodiments, the pharmaceutical composition comprises a tablet, capsule, pellet, or granule.

[0313] In some embodiments, the denatonium salt is present in the interior of the pharmaceutical composition, optionally wherein the denatonium salt is present in the interior of the tablet, capsule, pellet, or granule. Attorney Docket No.01309-0014-00PCT

[0314] In some embodiments, the denatonium salt is included in a composition comprising a therapeutically effective amount of the pharmaceutical agent. C. Methods of Treatment

[0315] Provided herein is a method for reducing a risk of use of a pharmaceutical agent for drug- facilitated sexual assault or other crime, comprising use of a denatonium salt to decrease the likelihood of improper ingestion by surreptitious administration of a pharmaceutical agent.

[0316] Also provided herein is a method for reducing a risk of drug abuse, comprising use of a denatonium salt to decrease the likelihood of ingestion of a pharmaceutical agent when dissolved or suspended in a liquid.

[0317] In some embodiments, the ingestion of the drug is unintentional.

[0318] Also provided herein is a method for making the taste of a pharmaceutical agent less palatable when improperly ingested, comprising adding a subclinical dose of a denatonium salt to a pharmaceutical composition.

[0319] Also provided herein is a method for making the taste of a pharmaceutical agent less palatable when dissolved or suspended in a liquid, comprising adding a subclinical dose of a denatonium salt to a pharmaceutical composition.

[0320] Also provided herein is a method for making a pharmaceutical composition detectable when dissolved or suspended in a liquid, comprising adding a subclinical dose of a denatonium salt to a pharmaceutical composition that includes a pharmaceutical agent such that when dissolved in a liquid, the taste of the liquid becomes bitter.

[0321] In some embodiments, the denatonium salt comprises denatonium acetate, denatonium citrate, denatonium tartrate, denatonium maleate, or denatonium saccharide.

[0322] In some embodiments, the denatonium salt comprises denatonium acetate.

[0323] In some embodiments, the denatonium salt comprises denatonium acetate monohydrate.

[0324] In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 50 mg.

[0325] In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 to 100 parts per million by weight or 0.01 to 0.1 milligrams per milliliter. Attorney Docket No.01309-0014-00PCT

[0326] In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 to 100 parts per million by weight. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.05 part per million by weight, about 0.1 part per million by weight, or about 0.5 parts per million by weight. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 part per million by weight, about 2 parts per million by weight, about 3 parts per million by weight, about 4 parts per million by weight, about 5 parts per million by weight, about 6 parts per million by weight, about 7 parts per million by weight, about 8 parts per million by weight, about 9 parts per million by weight, or about 10 parts per million by weight. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1-10 parts per million by weight, e.g., about 1-2 parts per million by weight, about 2-3 parts per million by weight, about 3-4 parts per million by weight, about 4- 5 parts per million by weight, about 5-6 parts per million by weight, about 6-7 parts per million by weight, about 7-8 parts per million by weight, about 8-9 parts per million by weight, or about 9-10 parts per million by weight.

[0327] In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 part per million by weight.

[0328] In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 2 parts per million by weight.

[0329] In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 parts per million by weight.

[0330] In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 parts per million by weight. Attorney Docket No.01309-0014-00PCT

[0331] In some embodiments, the denatonium salt is included in a composition comprising a therapeutically effective amount of the pharmaceutical agent.

[0332] In some embodiments, the denatonium salt and the pharmaceutical agent are present in a pharmaceutical composition that comprises a coating.

[0333] In some embodiments, the coating comprises a cellulose derivative, a vinyl polymer, or a polymethacrylate.

[0334] In some embodiments, the coating comprises a cellulose derivative and the cellulose derivative comprises hydroxypropyl methylcellulose, methylcellulose, or hydroxypropyl cellulose.

[0335] In some embodiments, the coating comprises a vinyl polymer and the vinyl polymer comprises polyvinyl alcohol or polyvinylpyrrolidone.

[0336] In some embodiments, the coating comprises a polymethacrylate and the polymethacrylate comprises a copolymer of butyl methacrylate, methacrylate, or methyl methacrylate.

[0337] In some embodiments, the pharmaceutical agent is comprises an agent that causes drowsiness, an agent that depresses the central nervous system, an agent that alters consciousness, an agent that impairs decision making, an agent that lowers inhibitions, an opioid, a narcotic, a psychoactive depressant, a sedative, a hypnotic, an anxiolytic, a benzodiazepine, a non-benzodiazepine, a z-drug, an anti-psychotic, a stimulant, a hallucinogen, a euphoriant, an anti-cholinergic, an anti-histamine, or an anesthetic.

[0338] Also provided herein is a method of making a date rape drug ineffective for drug- facilitated sexual assault, comprising including a denatonium salt in a pharmaceutical composition comprising the date rape drug.

[0339] In some embodiments, a therapeutically effective amount of the date rape drug is provided.

[0340] In some embodiments, the date rape drug is ingested unintentionally by a subject.

[0341] In some embodiments, the date rape drug causes an effect in a subject.

[0342] In some embodiments, the effect comprises impaired judgment, or sedation.

[0343] In some embodiments, the effect makes a subject more vulnerable to sexual assault.

[0344] In some embodiments, the pharmaceutical composition is a solid pharmaceutical composition. Attorney Docket No.01309-0014-00PCT

[0345] In some embodiments, the pharmaceutical composition comprises a tablet, capsule, pellet, or granule.

[0346] In some embodiments, the denatonium salt is present in the interior of the pharmaceutical composition, optionally wherein the denatonium salt is present in the interior of the tablet, capsule, pellet, or granule. D. Pharmaceutical Agents

[0347] In some embodiments, the pharmaceutical agent is used, or is capable of being used, for drug-facilitated sexual assault or other crime. The pharmaceutical agent can be an agent that causes drowsiness, an agent that depresses the central nervous system, an agent that alters consciousness, an agent that impairs decision making, an agent that lowers inhibitions, an opioid, a narcotic, a psychoactive depressant, a sedative, a hypnotic, an anxiolytic, a benzodiazepine, a non-benzodiazepine, a z-drug, an anti-psychotic, a stimulant, a hallucinogen, a euphoriant, an anti-cholinergic, an antihistamine, or an anesthetic.

[0348] In some embodiments, the pharmaceutical agent is used for drug-facilitated sexual assault or other crime. In some embodiments, the pharmaceutical agent is an agent that causes drowsiness. In some embodiments, the pharmaceutical agent is an agent that depresses the central nervous system. In some embodiments, the pharmaceutical agent is an agent that alters consciousness. In some embodiments, the pharmaceutical agent is an agent that impairs decision making. In some embodiments, the pharmaceutical agent is an agent that lowers inhibitions. In some embodiments, the pharmaceutical agent is an opioid. In some embodiments, the pharmaceutical agent is a narcotic. In some embodiments, the pharmaceutical agent is a psychoactive depressant. In some embodiments, the pharmaceutical agent is a sedative. In some embodiments, the pharmaceutical agent is a hypnotic. In some embodiments, the pharmaceutical agent is an anxiolytic. In some embodiments, the pharmaceutical agent is a benzodiazepine. In some embodiments, the pharmaceutical agent is a non-benzodiazepine. In some embodiments, the pharmaceutical agent is a z-drug. In some embodiments, the pharmaceutical agent is an anti- psychotic. In some embodiments, the pharmaceutical agent is a stimulant. In some embodiments, the pharmaceutical agent is a hallucinogen. In some embodiments, the pharmaceutical agent is a euphoriant. In some embodiments, the pharmaceutical agent is an anti-cholinergic. In some embodiments, the pharmaceutical agent is an antihistamine. In some embodiments, the pharmaceutical agent is an anesthetic. Attorney Docket No.01309-0014-00PCT

[0349] Exemplary pharmaceutical agents include gamma-hydroxybutyrate (also known as “GHB”), flunitrazepam (e.g., Rohypnol), ketamine, alcohol, 4-hydroxybutanoic acid, 4- hydroxypentanoic acid, zolpidem, diazepam (e.g., Valium), alprazolam (e.g., Xanax), triazolam (e.g., Halcion), lorazepam (e.g., Ativan), clonazepam (e.g., Klonopin), non-benzodiazepine hypnotics, opioids, scopolamine, diphenhydramine (e.g., Benadryl), diphenhydramine HCl (e.g., Tylenol PM, Dimetapp), diphenhydramine citrate (e.g., Advil PM), diphenhydramine hydrochloride (e.g., Unisom SleepGels), dimenhydrinate (e.g., Dramamine), doxylamine (e.g., Unisom SleepTabs), diazepam, eszopiclone (e.g., Lunesta), zaleplon (e.g., Sonata), or zolpidem (e.g., Ambien, Ambien CR, Edluar, Zolpimist). III. Dosing

[0350] In some embodiments, a denatonium salt is included in a composition comprising a pharmaceutical agent, which can be any of those described elsewhere herein.

[0351] In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 50 mg.

[0352] In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 5 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 10 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 15 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 20 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 25 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 30 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 35 mg. In some embodiments, the denatonium salt is included in a composition Attorney Docket No.01309-0014-00PCT comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 40 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 45 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 mg to about 10 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 mg to about 15 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 mg to about 20 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 mg to about 25 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 mg to about 30 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 mg to about 35 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 mg to about 40 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 mg to about 45 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 mg to about 50 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 mg to about 15 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 mg to about 20 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 mg to about 25 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is Attorney Docket No.01309-0014-00PCT present in said composition in a dose of about 10 mg to about 30 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 mg to about 35 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 mg to about 40 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 mg to about 45 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 mg to about 50 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 15 mg to about 20 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 15 mg to about 25 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 15 mg to about 30 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 15 mg to about 35 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 15 mg to about 40 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 15 mg to about 45 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 15 mg to about 50 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20 mg to about 25 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20 mg to about 30 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20 mg to about Attorney Docket No.01309-0014-00PCT 35 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20 mg to about 40 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20 mg to about 45 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20 mg to about 50 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 25 mg to about 30 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 25 mg to about 35 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 25 mg to about 40 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 25 mg to about 45 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 25 mg to about 50 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30 mg to about 35 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30 mg to about 40 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30 mg to about 45 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30 mg to about 50 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 35 mg to about 40 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 35 mg to about 45 mg. In some embodiments, the denatonium salt is included in a Attorney Docket No.01309-0014-00PCT composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 35 mg to about 50 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 40 mg to about 45 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 40 mg to about 50 mg. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 45 mg to about 50 mg.

[0353] In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 to 100 parts per million by weight or 0.01 to 0.1 milligrams per milliliter.

[0354] In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.05 part per million by weight. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.1 part per million by weight. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.5 parts per million by weight.

[0355] In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 part per million by weight. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 2 parts per million by weight. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 parts per million by weight. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 parts per million by weight. Attorney Docket No.01309-0014-00PCT

[0356] In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 to 100 parts per million.

[0357] In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 to 20 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 to 30 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 to 40 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 to 50 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 to 60 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 to 70 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 to 80 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 to 90 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20 to 30 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20 to 40 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20 to 50 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20 to 60 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the Attorney Docket No.01309-0014-00PCT pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20 to 70 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20 to 80 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20 to 90 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 20 to 100 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30 to 40 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30 to 50 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30 to 60 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30 to 70 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30 to 80 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30 to 90 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 30 to 100 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 40 to 50 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 40 to 60 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 40 to 70 parts per million. In some embodiments, the denatonium Attorney Docket No.01309-0014-00PCT salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 40 to 80 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 40 to 90 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 40 to 100 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 50 to 60 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 50 to 70 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 50 to 80 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 50 to 90 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 50 to 100 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 60 to 70 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 60 to 80 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 60 to 90 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 60 to 100 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 70 to 80 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about Attorney Docket No.01309-0014-00PCT 70 to 90 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 70 to 100 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 80 to 90 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 80 to 100 parts per million. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 90 to 100 parts per million.

[0358] In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.01 to 0.1 milligrams per milliliter.

[0359] In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.01 to 0.02 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.01 to 0.03 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.01 to 0.04 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.01 to 0.05 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.01 to 0.06 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.01 to 0.07 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.01 to 0.08 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said Attorney Docket No.01309-0014-00PCT composition in a dose of about 0.01 to 0.09 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.02 to 0.03 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.02 to 0.04 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.02 to 0.05 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.02 to 0.06 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.02 to 0.07 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.02 to 0.08 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.02 to 0.09 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.02 to 0.1 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.03 to 0.04 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.03 to 0.05 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.03 to 0.06 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.03 to 0.07 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.03 to 0.08 milligrams per Attorney Docket No.01309-0014-00PCT milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.03 to 0.09 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.03 to 0.1 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.04 to 0.05 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.04 to 0.06 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.04 to 0.07 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.04 to 0.08 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.04 to 0.09 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.04 to 0.1 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.05 to 0.06 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.05 to 0.07 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.05 to 0.08 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.05 to 0.09 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.05 to 0.1 milligrams per milliliter. In some embodiments, the denatonium salt is included in a Attorney Docket No.01309-0014-00PCT composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.06 to 0.07 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.06 to 0.08 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.06 to 0.09 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.06 to 0.1 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.07 to 0.08 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.07 to 0.09 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.07 to 0.1 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.08 to 0.09 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.08 to 0.1 milligrams per milliliter. In some embodiments, the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 0.09 to 0.1 milligrams per milliliter. IV. Coatings

[0360] When manufacturing pharmaceutical compositions such as finished tablet dosage forms, a film coating is often applied as an aqueous or solvent-based polymer system in coating pans or in a fluid-bed. The function of the coating may include improving esthetics, providing taste masking, and / or modifying drug release.

[0361] Examples of film coatings include, but are not limited to, cellulose derivatives (such as hydroxypropyl methylcellulose, methylcellulose, hydroxypropyl cellulose), vinyl polymers (such as polyvinyl alcohol, polyvinylpyrrolidone), polymethacrylates (such as copolymers of butyl Attorney Docket No.01309-0014-00PCT methacrylate, methacrylate, methyl methacrylate), other polymers (such as modified starches, polysaccharides), or any additional film coating formula constructed from polymers, plasticizers, surfactants or other appropriate additives that serve purposes including pharmaceutical composition protection, masking of taste of odors, improving mechanical strength, or facilitating product handling.

[0362] In some embodiments, the denatonium salt and the pharmaceutical agent are present in a pharmaceutical composition that comprises a coating. In some embodiments, the pharmaceutical composition comprises a coating. In some embodiments, the date rape drug is present in a pharmaceutical composition that comprises a coating.

[0363] In some embodiments, the coating has the property of masking the bitter taste of the denatonium salt when the pharmaceutical composition is taken or used as prescribed or is ingested whole.

[0364] In some embodiments, the coating has the property of not masking the bitter taste of the denatonium salt when the pharmaceutical composition is crushed, ground, or dissolved in a food or beverage.

[0365] In some embodiments, the coating is a film coating.

[0366] In some embodiments, the film coating comprises a cellulose derivative (such as hydroxypropyl methylcellulose, methylcellulose, hydroxypropyl cellulose), a vinyl polymer (such as polyvinyl alcohol, polyvinylpyrrolidone), or a polymethacrylate (such as a copolymer of butyl methacrylate, methacrylate, methyl methacrylate). In other embodiments, the film coating comprises other polymers (such as modified starches, polysaccharides), or any additional film coating formula constructed from polymers, plasticizers, surfactants or other appropriate additives that serve purposes including pharmaceutical composition protection, masking of taste of odors, improving mechanical strength, or facilitating product handling.

[0367] In some embodiments, the film coating comprises a cellulose derivative (such as hydroxypropyl methylcellulose, methylcellulose, hydroxypropyl cellulose).

[0368] In some embodiments, the film coating comprises a vinyl polymer (such as polyvinyl alcohol, polyvinylpyrrolidone).

[0369] In some embodiments, the film coating comprises a polymethacrylate (such as copolymers of butyl methacrylate, methacrylate, methyl methacrylate).

[0370] In some embodiments, the film coating comprises a modified starch or polysaccharide. Attorney Docket No.01309-0014-00PCT

[0371] In some embodiments, the film coating comprises a film coating formula constructed from polymers, plasticizers, surfactants or other appropriate additives that serve purposes including pharmaceutical composition protection, masking of taste of odors, improving mechanical strength, or facilitating product handling. V. Methods of Reducing Risk

[0372] Provided herein is a method for reducing a risk of use of a pharmaceutical agent for drug- facilitated sexual assault or other crime, comprising use of a denatonium salt to decrease the likelihood of improper ingestion by surreptitious administration of a pharmaceutical agent.

[0373] Also provided herein is a method for reducing a risk of drug abuse, comprising use of a denatonium salt to decrease the likelihood of ingestion of a pharmaceutical agent when dissolved or suspended in a liquid.

[0374] In some embodiments, the ingestion of the drug is unintentional.

[0375] Such methods can comprise incorporating the denatonium salt into a pharmaceutical composition with the pharmaceutical agent. The denatonium salt and the pharmaceutical agent can be any of those described elsewhere herein. VI. Methods of Making

[0376] Provided herein is a method for making the taste of a pharmaceutical agent less palatable when improperly ingested, comprising adding a subclinical dose of a denatonium salt to a pharmaceutical composition.

[0377] Also provided herein is a method for making the taste of a pharmaceutical agent less palatable when dissolved or suspended in a liquid, comprising adding a subclinical dose of a denatonium salt to a pharmaceutical composition.

[0378] Also provided herein is a method for making a pharmaceutical composition detectable when dissolved or suspended in a liquid, comprising adding a subclinical dose of a denatonium salt to a pharmaceutical composition that includes a pharmaceutical agent such that when dissolved in a liquid, the taste of the liquid becomes bitter.

[0379] Also provided herein is a method of making a date rape drug ineffective for sexual assault, comprising including a denatonium salt in a pharmaceutical composition of the date rape drug. Attorney Docket No.01309-0014-00PCT

[0380] The denatonium salt and the pharmaceutical agent can be any of those described elsewhere herein. EXAMPLES Example 1: Bitter Taste Aversion

[0381] A study was performed with two participants, in which dilutions of denatonium acetate monohydrate (DAM), at concentrations between 1.0 and 10.0 ppm in water or an electrolyte beverage, were assessed by taste. The water and electrolyte beverage were undrinkable due to significant bitter taste upon addition of DAM at 1-10 ppm. This represents between 0.5 and 5.0 mg of DAM in a 500 mL beverage such that even if the entire drink was consumed, the full dose of DAM would result in an undetectable systemic exposure (~1%) at a fraction (1 / 1600th to 1 / 160th) of the maximum clinical dose of 800 mg / day. Materials and Methods

[0382] The drug substance is denatonium acetate monohydrate. It is a small molecule TAS2R agonist.

[0383] Chemical Structure and Properties of DAM Drug Substance:

[0384] IUPAC chemical name: N-Benzyl-2-(2,6-dimethylanilino)-N,N-diethyl-2-oxoethan-1- aminium acetate (monohydrate).

[0385] Molecular formula: C23H32N2O3•H2O.

[0386] Molecular weight: 402.53 g / mol.

[0387] The DAM drug substance is a white to almost white to light yellow crystalline solid. It is freely soluble in purified water, ethanol (200 proof), isopropyl alcohol (IPA), and slightly soluble in acetone. Compound Formulation

[0388] DAM was stored at room temperature pending use in formulation and was formulated immediately before the study at concentrations between 1.0 and 10.0 ppm, using a correction Attorney Docket No.01309-0014-00PCT factor (for the salt form) of 1.23. The vehicles used for administration of DAM were filtered water or Gatorade. Study Design

[0389] Starting at approximately 10 AM on the afternoon of testing, patients withheld consumption of food or beverages, resulting in an approximately 4-hour fast prior to testing. At 2 PM the test solutions were formulated, and taste testing began at 2:15 PM. Tasting of the test solutions was performed in a random order. After each taste test, subjects rinsed frequently with untreated beverages and ate a variety of foods for 5-10 minutes to alleviate the persistent bitter taste. Table 1. Study Design Subject Sex Vehicle Dose Dose Dose Dose Subjective (oral Volume Conc. Frequency Endpoints

[0390] Bitterness was detected immediately after tasting with dose-dependent intensity and a threshold of extreme bitterness at approximately 2 ppm. One subject noted that the Gatorade + DAM solutions were slightly less bitter at concentrations less than 5 ppm, however still not drinkable. In all cases, bitterness was detected immediately after drinking, and persisted for 5 - 10 minutes. Table 2. Results from Bitter Taste Aversion Study Subject Treatment Bitter Taste Subjective Measures P t P Milli n n Attorney Docket No.01309-0014-00PCT 2 Water Not bitter, Very bitter, Extreme Extreme Extreme would drink would not bitter, bitter, bitter, a ain drink a ain would not would not would not n n f DAM were aversive and characterized by strong and persistent bitter taste that continued for 5- 10 minutes after tasting.

Claims

Attorney Docket No.01309-0014-00PCT CLAIMS What is claimed is:

1. A pharmaceutical composition comprising a denatonium salt and a pharmaceutical agent, wherein the pharmaceutical agent is used, or is capable of being used, for drug-facilitated sexual assault or other crime and / or comprises an agent that causes drowsiness, an agent that depresses the central nervous system, an agent that alters consciousness, an agent that impairs decision making, an agent that lowers inhibitions, an opioid, a narcotic, a psychoactive depressant, a sedative, a hypnotic, an anxiolytic, the benzodiazepine or non- benzodiazepine class or z-drug, an anti-psychotic, a stimulant, a hallucinogen, a euphoriant, an anti-cholinergic, an anti-histamine, or an anesthetic.

2. The pharmaceutical composition of any one of the preceding claims, wherein the denatonium salt comprises denatonium acetate, denatonium citrate, denatonium tartrate, denatonium maleate, or denatonium saccharide.

3. The pharmaceutical composition of any one of the preceding claims, wherein the denatonium salt comprises denatonium acetate.

4. The pharmaceutical composition of any one of the preceding claims, wherein the denatonium salt comprises denatonium acetate monohydrate.

5. The pharmaceutical composition of any one of the preceding claims, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 50 mg.

6. The pharmaceutical composition of any one of the preceding claims, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 to 100 parts per million by weight or 0.01 to 0.1 milligrams per milliliter.

7. The pharmaceutical composition of claim 6, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 part per million by weight.

8. The pharmaceutical composition of claim 6, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 2 parts per million by weight.Attorney Docket No.01309-0014-00PCT 9. The pharmaceutical composition of claim 6, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 parts per million by weight.

10. The pharmaceutical composition of claim 6, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 parts per million by weight.

11. The pharmaceutical composition of any one of the preceding claims, wherein the denatonium salt is included in a composition comprising a therapeutically effective amount of the pharmaceutical agent.

12. The pharmaceutical composition of any one of the preceding claims, wherein the pharmaceutical composition comprises a coating.

13. The pharmaceutical composition of claim 12, wherein the coating comprises a cellulose derivative, a vinyl polymer, or a polymethacrylate.

14. The pharmaceutical composition of claim 12 or 13, wherein the coating comprises a cellulose derivative and the cellulose derivative comprises hydroxypropyl methylcellulose, methylcellulose, or hydroxypropyl cellulose.

15. The pharmaceutical composition of claim 12 or 13, wherein the coating comprises a vinyl polymer and the vinyl polymer comprises polyvinyl alcohol or polyvinylpyrrolidone.

16. The pharmaceutical composition of claim 12 or 13, wherein the coating comprises a polymethacrylate and the polymethacrylate comprises a copolymer of butyl methacrylate, methacrylate, or methyl methacrylate.

17. The pharmaceutical composition of any one of the preceding claims, wherein the coating has the property of masking the bitter taste of the denatonium salt when the pharmaceutical composition is taken or used as prescribed or is ingested whole.

18. The pharmaceutical composition of any one of the preceding claims, wherein the coating has the property of not masking the bitter taste of the denatonium salt when the pharmaceutical composition is crushed, ground, or dissolved in a food or beverage.

19. The pharmaceutical composition of any one of the preceding claims, wherein the pharmaceutical agent comprises an agent that causes drowsiness, an agent that depresses the central nervous system, an agent that alters consciousness, an agent that impairs decision making, an agent that lowers inhibitions, an opioid, a narcotic, a psychoactive depressant, aAttorney Docket No.01309-0014-00PCT sedative, a hypnotic, an anxiolytic, a benzodiazepine, a non-benzodiazepine, a z-drug, an anti-psychotic, a stimulant, a hallucinogen, a euphoriant, an anti-cholinergic, an anti- histamine, or an anesthetic.

20. The pharmaceutical composition of any one of claims 1-19, wherein the pharmaceutical composition is a solid pharmaceutical composition.

21. The pharmaceutical composition of any one of claims 1-19, wherein the pharmaceutical composition comprises a tablet, capsule, pellet, or granule.

22. The pharmaceutical composition of any one of claims 1-19, wherein the denatonium salt is present in the interior of the pharmaceutical composition, optionally wherein the denatonium salt is present in the interior of the tablet, capsule, pellet, or granule.

23. A method for reducing a risk of use of a pharmaceutical agent for drug-facilitated sexual assault or other crime, comprising use of a denatonium salt to decrease the likelihood of improper ingestion by surreptitious administration of a pharmaceutical agent.

24. The method of claim 23, wherein the denatonium salt comprises denatonium acetate, denatonium citrate, denatonium tartrate, denatonium maleate, or denatonium saccharide.

25. The method of claim 23 or 24, wherein the denatonium salt comprises denatonium acetate.

26. The method of claim 23 or 24, wherein the denatonium salt comprises denatonium acetate monohydrate.

27. The method of any one of claims 23-26, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 mg to about 50 mg.

28. The method of any one of claims 23-27, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 to 100 parts per million by weight or 0.01 to 0.1 milligrams per milliliter.

29. The method of claim 28, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 1 part per million by weight.

30. The method of claim 28, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 2 parts per million by weight.Attorney Docket No.01309-0014-00PCT 31. The method of claim 28, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 5 parts per million by weight.

32. The method of claim 28, wherein the denatonium salt is included in a composition comprising the pharmaceutical agent, and the denatonium salt is present in said composition in a dose of about 10 parts per million by weight.

33. The method of any one of claims 23-32, wherein the denatonium salt is included in a composition comprising a therapeutically effective amount of the pharmaceutical agent.

34. The method of any one of claims 23-33, wherein the denatonium salt and the pharmaceutical agent are present in a pharmaceutical composition that comprises a coating.

35. The method of claim 34, wherein the coating comprises a cellulose derivative, a vinyl polymer, or a polymethacrylate.

36. The method of claim 34 or 35, wherein the coating comprises a cellulose derivative and the cellulose derivative comprises hydroxypropyl methylcellulose, methylcellulose, or hydroxypropyl cellulose.

37. The method of claim 34 or 35, wherein the coating comprises a vinyl polymer and the vinyl polymer comprises polyvinyl alcohol or polyvinylpyrrolidone.

38. The method of claim 34 or 35, wherein the coating comprises a polymethacrylate and the polymethacrylate comprises a copolymer of butyl methacrylate, methacrylate, or methyl methacrylate.

39. The method of any one of claims 23-38, wherein the pharmaceutical agent is comprises an agent that causes drowsiness, an agent that depresses the central nervous system, an agent that alters consciousness, an agent that impairs decision making, an agent that lowers inhibitions, an opioid, a narcotic, a psychoactive depressant, a sedative, a hypnotic, an anxiolytic, a benzodiazepine, a non-benzodiazepine, a z-drug, an anti-psychotic, a stimulant, a hallucinogen, a euphoriant, an anti-cholinergic, an anti-histamine, or an anesthetic.

40. A method for reducing a risk of drug abuse, comprising use of a denatonium salt to decrease the likelihood of ingestion of a pharmaceutical agent when dissolved or suspended in a liquid.Attorney Docket No.01309-0014-00PCT 41. A method for making the taste of a pharmaceutical agent less palatable when improperly ingested, comprising adding a subclinical dose of a denatonium salt to a pharmaceutical composition.

42. A method for making the taste of a pharmaceutical agent less palatable when dissolved or suspended in a liquid, comprising adding a subclinical dose of a denatonium salt to a pharmaceutical composition.

43. A method for making a pharmaceutical composition detectable when dissolved or suspended in a liquid, comprising adding a subclinical dose of a denatonium salt to a pharmaceutical composition that includes a pharmaceutical agent such that when dissolved in a liquid, the taste of the liquid becomes bitter.

44. A method of making a date rape drug ineffective for drug-facilitated sexual assault, comprising including a denatonium salt in a pharmaceutical composition comprising the date rape drug.

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