Abuse-deterrent multi-layer pharmaceutical composition comprising an opioid antagonist and an opioid agonist
First Claim
Patent Images
1. A method of treating moderate to severe pain in a human, the method comprising:
- orally administering to said human an intact composition in an amount sufficient to treat the moderate to severe pain;
wherein the composition comprises a plurality of multi-layer pellets comprising;
a. a water-soluble core;
b. an opioid antagonist comprising layer coating the core, wherein the opioid antagonist is selected from the group consisting of naltrexone, naloxone, nalmefene, cyclazacine, levallorphan, salts of these molecules, and combinations thereof;
c. a sequestering polymer layer coating the opioid antagonist comprising layer;
d. an osmotic pressure regulating agent comprising layer coating the sequestering polymer layer, wherein the osmotic pressure regulating agent is selected from the group consisting of sodium chloride, sodium bromide, sodium iodide, hydroxypropyl methyl cellulose, and combinations thereof;
e. an opioid agonist comprising layer coating the osmotic pressure regulating agent comprising layer, wherein the opioid agonist is selected from the group consisting of morphine, oxycodone, hydrocodone, hydromorphone, dihydrocodeine, codeine, dihydromorphine, buprenorphine, salts of these molecules, and combinations thereof; and
f. a controlled release layer coating the opioid agonist comprising layer;
wherein the sequestering polymer layer comprisescopolymers of acrylic and methacrylic acid esters with quaternary ammonium groups, a surfactant in an amount from 1.6% to 6.3% of the copolymers of acrylic and methacrylic acid esters with quaternary ammonium groups on a weight-to-weight basis, and talc in an amount of from 75% to 125% of the copolymers of acrylic and methacrylic acid esters with quaternary ammonium groups on a weight-to-weight basis;
wherein the surfactant is selected from the group consisting of sodium lauryl sulfate, sodium docusate, dioctyl sodium sulphosuccinate, sodium lauryl sarcosinate, sodium methyl cocyl taurate, magnesium lauryl sulfate, dioctyl sodiumsulfosuceinate, sodiumdodecylbenzene sulfonate, and combinations thereof; and
wherein when tested by a testing method, the composition sequesters at least 80% of the opioid antagonist as determined at 73 hours from the start of the testing method,wherein the testing method comprises first placing the composition in 500 mL of a 0.1 N HCl solution for 1 hour at 37°
C. using USP paddle method, 100 rotations per minute, and then placing the composition in 500 mL of a pH 7.5, 0.05 M phosphate buffer, for 72 hours at 37°
C. using USP paddle method, 100 rotations per minute, and then determining the amount of the opioid antagonist sequestered.
9 Assignments
0 Petitions
Accused Products
Abstract
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.
301 Citations
65 Claims
-
1. A method of treating moderate to severe pain in a human, the method comprising:
- orally administering to said human an intact composition in an amount sufficient to treat the moderate to severe pain;
wherein the composition comprises a plurality of multi-layer pellets comprising; a. a water-soluble core; b. an opioid antagonist comprising layer coating the core, wherein the opioid antagonist is selected from the group consisting of naltrexone, naloxone, nalmefene, cyclazacine, levallorphan, salts of these molecules, and combinations thereof; c. a sequestering polymer layer coating the opioid antagonist comprising layer; d. an osmotic pressure regulating agent comprising layer coating the sequestering polymer layer, wherein the osmotic pressure regulating agent is selected from the group consisting of sodium chloride, sodium bromide, sodium iodide, hydroxypropyl methyl cellulose, and combinations thereof; e. an opioid agonist comprising layer coating the osmotic pressure regulating agent comprising layer, wherein the opioid agonist is selected from the group consisting of morphine, oxycodone, hydrocodone, hydromorphone, dihydrocodeine, codeine, dihydromorphine, buprenorphine, salts of these molecules, and combinations thereof; and f. a controlled release layer coating the opioid agonist comprising layer; wherein the sequestering polymer layer comprises copolymers of acrylic and methacrylic acid esters with quaternary ammonium groups, a surfactant in an amount from 1.6% to 6.3% of the copolymers of acrylic and methacrylic acid esters with quaternary ammonium groups on a weight-to-weight basis, and talc in an amount of from 75% to 125% of the copolymers of acrylic and methacrylic acid esters with quaternary ammonium groups on a weight-to-weight basis; wherein the surfactant is selected from the group consisting of sodium lauryl sulfate, sodium docusate, dioctyl sodium sulphosuccinate, sodium lauryl sarcosinate, sodium methyl cocyl taurate, magnesium lauryl sulfate, dioctyl sodiumsulfosuceinate, sodiumdodecylbenzene sulfonate, and combinations thereof; and wherein when tested by a testing method, the composition sequesters at least 80% of the opioid antagonist as determined at 73 hours from the start of the testing method, wherein the testing method comprises first placing the composition in 500 mL of a 0.1 N HCl solution for 1 hour at 37°
C. using USP paddle method, 100 rotations per minute, and then placing the composition in 500 mL of a pH 7.5, 0.05 M phosphate buffer, for 72 hours at 37°
C. using USP paddle method, 100 rotations per minute, and then determining the amount of the opioid antagonist sequestered. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65)
- orally administering to said human an intact composition in an amount sufficient to treat the moderate to severe pain;
-
20. A method of treating moderate to severe pain in a human, the method comprising:
- orally administering to said human an intact composition in an amount sufficient to treat the moderate to severe pain;
wherein the composition comprises a plurality of multi-layer pellets comprising; a. a water-soluble core; b. an opioid antagonist comprising layer coating the core, wherein the opioid antagonist is selected from the group consisting of naltrexone, naloxone, nalmefene, cyclazacine, levallorphan, salts of these molecules, and combinations thereof; c. a sequestering polymer layer coating the opioid antagonist comprising layer; d. an osmotic pressure regulating agent comprising layer coating the sequestering polymer layer, wherein the osmotic pressure regulating agent is selected from the group consisting of sodium chloride, sodium bromide, sodium iodide, hydroxypropyl methyl cellulose, and combinations thereof; e. an opioid agonist comprising layer coating the osmotic pressure regulating agent comprising layer, wherein the opioid agonist is selected from the group consisting of oxycodone, a salt of oxycodone, and combinations thereof; and f. a controlled release layer coating the opioid agonist comprising layer; wherein the sequestering polymer layer comprises copolymers of acrylic and methacrylic acid esters with quaternary ammonium groups, a surfactant in an amount from 1.6% to 6.3% of the copolymers of acrylic and methacrylic acid esters with quaternary ammonium groups on a weight-to-weight basis, and talc in an amount of from 75% to 125% of the copolymers of acrylic and methacrylic acid esters with quaternary ammonium groups on a weight-to-weight basis; wherein the surfactant is selected from the group consisting of sodium lauryl sulfate, sodium docusate, dioctyl sodium sulphosuccinate, sodium lauryl sarcosinate, sodium methyl cocyl taurate, magnesium lauryl sulfate, dioctyl sodiumsulfosuceinate, sodiumdodecylbenzene sulfonate, and combinations thereof; and wherein when tested by a testing method, the composition sequesters at least 80% of the opioid antagonist as determined at 73 hours from the start of the testing method, wherein the testing method comprises first placing the composition in 500 mL of a 0.1 N HCl solution for 1 hour at 37°
C. using USP paddle method, 100 rotations per minute, and then placing the composition in 500 mL of a pH 7.5, 0.05 M phosphate buffer, for 72 hours at 37°
C. using USP paddle method, 100 rotations per minute, and then determining the amount of the opioid antagonist sequestered.
- orally administering to said human an intact composition in an amount sufficient to treat the moderate to severe pain;
Specification
-
- Resources
Litigation Campaign Assessment
Thank you for your request. You will receive a custom alert email when the Litigation Campaign Assessment is available.
×
-
Current AssigneeAlpharma Pharmaceuticals LLC (Pfizer Inc.)
-
Original AssigneeAlpharma Pharmaceuticals LLC (Pfizer Inc.)
-
InventorsMatthews, Frank, Boehm, Garth, Tang, Lijuan, Liang, Alfred
-
Primary Examiner(s)Wax, Robert A
-
Assistant Examiner(s)AL-AWADI, DANAH J
-
Application NumberUS11/820,499Publication NumberTime in Patent Office1,764 DaysField of SearchNoneUS Class Current424/490CPC Class CodesA61K 31/485 Morphinan derivatives, e.g....A61K 9/16 Agglomerates; Granulates; M...A61K 9/167 with an outer layer or coat...A61K 9/1676 having a drug-free core wit...A61K 9/4808 characterised by the form o...A61K 9/50 Microcapsules having a gas,...A61K 9/5015 Organic compounds, e.g. fat...A61K 9/5026 obtained by reactions only ...A61K 9/5073 having two or more differen...A61K 9/5078 with drug-free coreA61P 25/04 Centrally acting analgesics...A61P 25/36 Opioid-abuseA61P 29/00 Non-central analgesic, anti...A61P 43/00 Drugs for specific purposes...
