Abuse resistant forms of immediate release oxymorphone, method of use and method of making
An abuse resistant oral pharmaceutical composition, comprising: a barrier layer, comprising a first polymer; a diffusion layer, comprising a second polymer, substantially covering the barrier layer, wherein the diffusion layer is bonded to the barrier layer and comprises a drug that is substantially homogeneously distributed within the second polymer and diffuses from the diffusion layer within the gastrointestinal (GI) tract; and optionally an expansion layer comprising an expandable polymer, wherein the expansion layer is substantially covered by the barrier layer. Methods of making the same and methods of using the same are also provided.
1. A method of treating pain in a patient in need thereof, comprising:
orally administering to the patient an immediate release abuse resistant pharmaceutical composition comprising a drug selected from the group consisting of any of oxymorphone and a pharmaceutically acceptable salt thereof in tablet unit dosage form, wherein the tablet dosage form comprises the following tablet layer:
an innermost expansion layer that does not contain any drug and comprises an expandable polymer selected from the group consisting of hydroxypropyl methylcellulose and polyacrylic acid,
a barrier layer that covers the expansion layer to an extent of more than 90% and comprises a first polymer that does not substantially dissolve in the gastrointestinal (GI) tract, wherein the first polymer is selected from the group consisting of polyacrylates and polyethylene glycol,
a diffusion layer that that covers the barrier later of more than 90% and is bonded to the barrier layer and comprises said drug being substantially homogeneously distributed within a second polymer selected from the group consisting of dispersions of methyl methacrylate and ethyl methacrylate, wherein the drug diffuses from the diffusion layer within the GI tract to treat pain,
wherein the pharmaceutical composition is configured such that when the pharmaceutical composition is physically compromised to produce particles having a particle size between 8 mesh and 500 mesh and exposed to a liquid comprising water and/or alcohol, the bond between the diffusion layer and the barrier layer is substantially preserved and the expandable polymer of the expansion layer absorbs at least a portion of the liquid and expands and/or forms a gel,
wherein the diffusion layer is the only drug-containing layer, and
wherein when the pharmaceutical composition is orally or intranasally administered in physically compromised form to a subject, the intensity of euphoria is lower than the intensity of the euphoria achieved after administration of a physically compromised bioequivalent composition not configured to deter abuse, and wherein the bond between the diffusion layer and the barrier layer is substantially preserved in an event of cutting or grinding to reduce a rate of release of the drug relative to when the tablet is orally administered.
2. The method of claim 1 , wherein the oxymorphone or pharmaceutically acceptable salt thereof is present in an amount of about 4 mg to about 800 mg.
3. The method of claim 1 , wherein the oxymorphone or pharmaceutically acceptable salt thereof comprises oxymorphone hydrochloride.
4. The method of claim 1 , wherein the diffusion layer has a thickness of about 1 to 30% of the thickness of the tablet unit dosage form.
5. The method of claim 1 , wherein the barrier layer has a thickness of about 5 to 50% of the thickness of the tablet unit dosage form.
6. The method of claim 1 , which reduces a euphoric effect of a physically compromised tablet upon administration or renders administration difficult or both.
7. The method of claim 6 , wherein when the tablet is physically compromised by cutting the physical bond between the diffusion layer and the barrier layer is substantially preserved, and a relative surface area of the diffusion layer increases only marginally, thereby preventing a significant increase of drug release.
8. The method of claim 1 , wherein the drug release from said pharmaceutical composition is independent of pH.
9. The method of claim of claim 1 , wherein the barrier layer comprises 10 to 60 wt. % of the tablet, and is applied immediately after said diffusion polymer and cured together to render the layers inseparable and resistant to smashing, crushing or grinding.
10. The method of claim 1 , wherein said barrier layer comprises an aqueous dispersion of ethyl acrylate and methyl methacrylate.
11. The method of claim 10 , wherein said aqueous dispersion is sprayed on the expansion layer.
12. The method of claim 11 , wherein the diffusion layer comprises said drug and an aqueous dispersion of ethyl acrylate and methyl methacrylate, which is applied immediately by spraying on said barrier layer, and curing said barrier layer and said diffusion layer together.
13. The method of claim 1 , wherein a hydroxypropylmethylcellulose seal coat is applied to the pharmaceutical composition.