Abuse-deterrent pharmaceutical compositions of opioids and other drugs

Abstract

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, a drug is modified to increase its lipophilicity. In preferred embodiments 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, but enzymatically degradable by enzymes present in the human gastrointestinal tract. The abuse-deterrent composition retards the release 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.

Description

[0001]This application claims priority to U.S. Ser. No. 60 / 393,876 filed Jul. 5, 2002 entitled “Abuse-Resistant Formulations of Oxycontin and Other Drugs” by Alexander M. Klibanov, Stephen L. Buchwald, Timothy M. Swager, and Whe-Yong Lo; U.S. Ser. No. 60 / 436,523 filed Dec. 23, 2002 by Alison B. Fleming, Roman V. Rariy, Alexander M. Klibanov, Whe-Yong Lo, and Jane Hirsh; U.S. Ser. No. 60 / 443,226 filed Jan. 28, 2003 by Jane Hirsh, Alison B. Fleming, Alexander M. Klibanov, and Whe-Yong Lo; U.S. Ser. No. 60 / 463,514 filed Apr. 15, 2003 by Jane C. Hirsh, Alison B. Fleming, Roman V. Rariy, Stephen L. Buchwald, and Timothy M. Swager; and U.S. Ser. No. 60 / 463,518 filed Apr. 15, 2003 by Jane C. Hirsh, Alison B. Fleming and Roman V. Rariy.BACKGROUND OF THE INVENTION[0002]The present invention is generally in the field of pharmaceutical compositions, and specifically relates to compositions that are designed to reduce the potential for improper administration of drugs that are subject to abuse....

AI Technical Summary

Benefits of technology

[0010]An abuse-deterrent pharmaceutical composition and the method of making and using the composition have been developed. The composition can be used to reduce the likelihood of improper administration of drugs, especially drugs such as oxycodone. The technology is useful for a number of other drugs where sustained release oral delivery is desired, and there is the potential for abuse if the drug dose is made immediately available for nasal, IV or oral administration. In the preferred embodiment, the drug is chemically modified to increase its lipophilicity. In other embodiments, the formulation contains lipophilic or water-insoluble materials or is made using a process which increases the lipophilicity and / or water-insolubility of the composition.

[0011]The abuse-deterrent composition retards the release of drug, even if the physical integrity of the dosage form is compromised (for example, by chopping with a blade or crushing) and the resulting material is placed in water, snorted, or swallowed. The composition thus provides a deterrent to common methods of improper administration including IV injection of drug dissolved in water and nasal or oral administration of the crushed formulation since drug will not be immediately released from the formulation. However, when administered as directed, the drug is slowly released (typically over a period of 4-18 hours) 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.

Problems solved by technology

The technology is useful for a number of other drugs where sustained release oral delivery is desired, and there is the potential for abuse if the drug dose is made immediately available for nasal, IV or oral administration.

The components of the resulting coated microparticles are not mutually soluble in water, organic solvents, or any combination thereof, so that in vitro degradation of the formulation will require more than one step.

Hence the drug is not easily extractable from such a formulation by conventional chemical means.

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