Pharmaceutical Compositions
Provided herein is a pharmaceutical composition comprising an antagonist, an agonist, a seal coat, and a sequestering polymer, wherein the antagonist, agonist, seal coat and at least one sequestering polymer are all components of a single unit, and wherein the seal coat forms a layer physically separating the antagonist from the agonist from one another. Methods for manufacturing such a pharmaceutical composition are also provided. Methods for treating pain using such compositions is also demonstrated.
1 . A pharmaceutical composition comprising oxycodone, an antagonist of oxycodone, a seal coat, and at least one sequestering polymer, wherein the seal coat physically separates the oxycodone from the antagonist in the intact form of the composition.
2 . A pharmaceutical composition comprising oxycodone and an antagonist of oxycodone on a sealed sugar sphere, wherein the oxycodone and antagonist are separated by a substantially impermeable barrier comprising a sequestering polymer, charge-neutralizing additive, and a sequestering polymer hydrophobicity-enhancing additive, wherein the agonist is substantially released and the antagonist is substantially sequestered upon administration to a human being.
3 . The composition of claim 2 wherein the sealed sugar sphere is sealed by a layer comprising a polymer insoluble in the gastrointestinal tract.
4 . The composition of claim 3 wherein the polymer is a cellulose.
5 . The composition of claim 4 wherein the cellulose is selected from the group consisting of ethylcellulose, cellulose acetate, cellulose propionate, cellulose acetate propionate, cellulose acetate butyrate, cellulose acetate phthalate, cellulose triacetate, and combinations thereof.
6 . The composition of claim 5 wherein the cellulose is ethylcellulose.
7 . The composition of claim 6 wherein the ethylcellulose is ethylcellulose N50.
8 . The composition of claim 2 wherein the sealed sugar sphere is coated by a composition comprising talc.
9 . The composition of claim 2 wherein the sealed sugar sphere wherein the layer further comprises a plasticizer.
10 . The composition of claim 9 wherein the plasticizer is selected from the group consisting of dibutyl sebacate, diethyl phthalate, triethyl citrate, tributyl citrate, and triacetin, an acetylated monoglyceride, a phthalate ester, and castor oil.
11 . The composition of claim 10 wherein the plasticizer is dibutyl sebacate.
12 . The composition of claim 2 wherein the layer further comprises an inert filler.
13 . The composition of claim 12 wherein the inert filler is a metal stearate.
14 . The composition of claim 13 wherein the metal stearate is magnesium stearate.
15 . The composition of claim 1 or 2 the sequestering polymer is a Eudragit® polymer.
16 . The composition of claim 15 wherein the sequestering polymer hydrophobicity-enhancing additive is talc.
17 . The composition of claim 2 wherein the charge-neutralizing additive is a surfactant.
18 . The composition of claim 17 wherein the surfactant is sodium lauryl sulfate.
19 . The composition of claim 17 or 18 wherein the surfactant is present at approximately 4% on a weight-to-weight basis with respect to the sequestering polymer.
20 . The composition of claim 2 further comprising an osmotic pressure regulating agent above the substantially impermeable barrier.
21 . The composition of claim 20 wherein the osmotic pressure regulating agent comprises chloride ions.
22 . The composition of claim 21 wherein the osmotic pressure regulating agent is sodium chloride.
23 . A method of treating pain in a person comprising administering to the person a composition of any one of claims 1 - 22 .
24 . The method of claim 23 wherein pain is substantially relieved in the patient.
25 . The method of claim 23 wherein pain is significantly decreased following administration of the composition to a patient.