Abuse-deterrent drug formulations
An abuse-deterrent pharmaceutical composition has been developed to reduce the likelihood of improper administration of drugs, especially drugs such as opiods. In the preferred embodiment, the drug is modified to increase its lipophilicity by forming a salt between the drug and one or more fatty acids wherein the concentration of the one or more fatty acids is one to 15 times the molar amount of the active agent, preferably two to ten times the molar amount of the active agent. In one embodiment the modified drug is homogeneously dispersed within microparticles composed of a material that is either slowly soluble or not soluble in water. In some embodiments the drug containing microparticles or drug particles are coated with one or more coating layers, where at least one coating is water insoluble and preferably organic solvent insoluble. The abuse-deterrent composition prevents the immediate release of a substantial portion of drug, even if the physical integrity of the formulation is compromised (for example, by chopping with a blade or crushing) and the resulting material is placed in water, snorted, or swallowed. However, when administered as directed, the drug is slowly released from the composition as the composition is broken down or dissolved gradually within the GI tract by a combination of enzymatic degradation, surfactant action of bile acids, and mechanical erosion.
1. An abuse-deterrent, therapeutically effective pharmaceutical composition comprising solid microparticles, wherein the microparticles comprise:
a. a fatty acid salt of a basic active agent prone to abuse, and
b. one or more carrier materials selected from the group consisting of waxes or wax-like substances and mixtures thereof;
wherein the process of making the microparticles comprises dissolving the active agent in free base form in a melt comprising one or more fatty acids, thereby forming a salt between the active agent and the one or more fatty acids, and wherein the one or more fatty acids are present in molar excess relative to the active agent.
2. The composition of claim 1 , wherein the one or more fatty acids are present in an amount ranging from 2 to 15 times the molar amount of active agent.
3. The composition of claim 1 , wherein the one or more fatty acids are present in an amount ranging from 2 to 10 times the molar amount of active agent.
4. The composition of claim 1 , wherein the one or more fatty acids are present in an amount ranging from 6.9 to 15 times the molar amount of active agent.
5. The composition of claim 1 , wherein the one or more fatty acids are present in an amount ranging from 6.9 to 10 times the molar amount of active agent.
6. The composition of claim 1 , wherein the one or more fatty acids is one or more C5 to C30 monovalent fatty acids, one or more C8 to C40 divalent fatty acids, or mixtures thereof.
7. The composition of claim 6 , wherein the one or more fatty acids is one or more C5 to C30 monovalent fatty acids selected from the group consisting of pentanoic acid, hexanoic (caproic) acid, heptanoic acid, octanoic (caprylic) acid, nonanoic acid, decanoic (capric) acid, undecanoic acid, dodecanoic (lauric) acid, tridecanoic acid, tetradecanoic (myristic) acid, pentadecanoic acid, hexadecanoic (palmitic) acid, heptadecanoic (margaric) acid, octadecanoic (stearic) acid, nonadecanoic acid, eicosanoic (arachidic) acid, heneicosanoic acid, docosanoic (behenic) acid, tricosanoic acid, tetracosanoic (lignoceric) acid, pentacosanoic acid, hexacosanoic acid, heptacosanoic acid, octacosanoic acid, nonacosanoic acid, triacontanoic acid, linoleic acid, oleic acid, and mixtures thereof.
8. The composition of claim 7 , wherein the one or more fatty acids is myristic acid.
9. The composition of claim 1 , wherein the one or more carrier materials are present in an amount of from 0.25 to 8 times by weight of the amount of the active agent.
10. The composition of claim 9 , wherein the one or more carrier materials are present in an amount of from 2 to 6 times by weight of the amount of the active agent.
11. The composition of claim 1 , wherein the carrier material is a wax selected from the group consisting of carnauba wax, beeswax, microcrystalline wax and mixtures thereof.
12. The composition of claim 11 , wherein the carrier material is a mixture of beeswax and carnauba wax.
13. The composition of claim 1 , wherein the active agent is oxycodone, the one or more fatty acids is myristic acid, and the carrier material comprises beeswax and carnauba wax.
14. A pharmaceutical dosage form comprising the composition of claim 1 .
15. A pharmaceutical dosage form comprising the composition of claim 13 .
16. The pharmaceutical dosage form of claim 14 , in the form of a capsule.
17. The pharmaceutical dosage form of claim 15 , in the form of a capsule.
18. The composition of claim 1 , wherein the active agent is selected from the group consisting of oxycodone, hydrocodone, morphine, oxymorphone, amphetamine, and methylphenidate.
19. The composition of claim 18 , wherein the active agent is oxycodone.
20. The composition of claim 18 , wherein the active agent is hydrocodone.