Abuse resistant pharmaceutical compositions
The present invention relates to a composition comprising pharmaceutical active ingredients which are susceptible to, or have potential for, abuse. The invention provides an oral pharmaceutical composition comprising a first population of beads and a second population of beads. The first bead population comprises a pharmaceutically active ingredient susceptible to, or having the potential for, abuse. The second bead population comprises a gelling agent and a coating substantially surrounding the gelling agent, but containing no pharmaceutically active ingredient. The first bead population and the second bead population are physically separable, but visually indistinguishable to the naked eye. Upon ingress of water into the second population of beads, the gelling agent is caused to swell forming a viscous mass inhibiting or preventing the extraction of the active ingredient.
1. A method of preparing an oral dosage form comprising a population of immediate release beads comprising an opioid and a population of gelling agent-containing beads comprising polyethylene oxide and a permeable or semi-permeable coating polymer, the method comprising the steps of:
a) independently preparing a solution comprising an opioid selected from the group consisting of benzylmorphine, bezitramide, buprenorphine, butorphanol, carfentanil, clonitazene, codeine, desomorphine, dextromoramide, dezocine, diacetylmorphine, diampromide, diamorphone, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, diphenoxylate, dioxaphetyl butyrate, diprenorphine, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene, etorphine, dihydroetorphine, fentanyl, hydrocodone, hydromorphone, β-hydroxy-3-methylfentanyl, hydroxypethidine, isomethadone, ketobemidone, levo-α-acetylmethadol, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, methadone, metopon, morphine, myrophine, nalmefene, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, nalbuphene, normorphine, norpipanone, o-methylnaltrexone, opium, oxycodone, oxymorphone, papaveretum, pentazocine, pethidine, phenadoxone, phenomorphan, phenazocine, phenoperidine, piminodine, piritramide, propheptazine, promedol, properidine, propoxyphene, remifentanil, sufentanil, tilidine, and tramadol, or pharmaceutically acceptable salts thereof;
b) applying sufficient amounts of the solution of step a) onto a sufficient amount of a first population of sugar spheres to produce the population of immediate release beads, wherein the population of immediate release beads is free of polyethylene oxide;
c) independently forming a binder solution by dissolving a binder in a solvent mixture comprising alcohol and water;
d) applying the binder solution and a sufficient amount of polyethylene oxide powder onto a sufficient amount of a second population of sugar spheres to produce polyethylene oxide layered sugar spheres;
e) independently forming a coating polymer mixture by mixing the permeable or semi-permeable polymer in a solvent mixture comprising alcohol, acetone and water;
f) applying the coating polymer mixture onto polyethylene oxide layered sugar spheres of step d) to form the population of gelling agent-containing beads, wherein the gelling agent-containing beads are free of the opioid;
g) mixing the immediate release beads and the gelling-agent containing beads in different proportions; and
h) incorporating the immediate release beads and the gelling agent-containing beads into the oral dosage form.
2. The method of claim 1 , wherein the opioid is selected from the group consisting of codeine, dihydrocodeine, hydrocodone, methadone, morphine and oxycodone.
3. The method of claim 1 , wherein the opioid is hydrocodone bitartrate.
4. The method of claim 1 , wherein the oral dosage form is a capsule.
5. The method of claim 4 , wherein the capsule comprises from 5 to 250 mg of hydrocodone.
6. The method of claim 5 , wherein the capsule comprises 20 mg of hydrocodone bitartrate.
7. The method of claim 5 , wherein the capsule comprises 50 mg of hydrocodone bitartrate.
8. The method of claim 4 , wherein the capsule comprises at least about 20 mg of polyethylene oxide.
9. The method of claim 1 , wherein the binder is povidone.
10. The method of claim 1 , wherein the semi-permeable polymer is selected from the group consisting of an ammonio methacrylate copolymer, and a methacrylic acid copolymer, or a combination thereof.