Abuse resistant capsule

Patent metadata

Field	Value
Publication number	US-11464747-B2
Application number	US-201916572148-A
Country	US
Kind code	B2
Filing date	Sep 16, 2019
Priority date	Mar 15, 2013
Publication date	Oct 11, 2022
Grant date	Oct 11, 2022

Abstract

The present invention is directed to an immediate release and extended release capsule or capsule fill which mitigates the abuse of abuse-susceptible active pharmaceutical ingredients by direct intravenous injection. The fill comprises a parenteral abuse resistant liquid formulation which when mixed with water and heated, results in a turbid, viscous or bubbling mixture that is not injectable with a standard insulin syringe. The abuse-susceptible active pharmaceutical ingredient is selected from the group consisting of opiates, opioids, tranquilizers, stimulants and narcotics.

First claim

The invention claimed is:

1. An immediate release parenteral abuse resistant capsule comprising a shell encapsulating a parenteral abuse resistant liquid comprising:
(a) an abuse-susceptible active pharmaceutical ingredient selected from the group consisting of opiates, opioids, tranquillizers, stimulants and narcotics;
(b) an ion exchange resin selected from the group consisting of polyacrilex resin, sodium polystyrene sulfonate, potassium polyacrilin, and colestyramine resin;
(c) 5.0 to 45.6 wt. % of a surfactant selected from polyoxyethylene (20) sorbitan monolaurate, -polyoxyethylene (20) sorbitan monooleate, macrogolglycerol hydroxystearate, macrogolglycerol ricinoleate, glycerolmonooleate 40, macrogolglycerol linoleate, linoleoyl macrogol-6 glycerides, propylene glycol monolaurate FCC, polyglycerol-6-dioleate, polyglycerol-3-dioleate, propylene glycol monocaprylate, sorbitanmonolaurate, sorbitanmonooleate, Vitamin E-polyethylenglycol-succinate, caprylocaproyl macrogol-8 glycerides, macrogol-32-glycerol-laurate, glycerylmonocaprate/caprylate, and a phosphatidylcholine concentrate; and
(d) 40 wt. % to 60 wt. % of a carrier comprising a hydrophilic carrier selected from macrogol 400, macrogol 600, macrogol 1500, propylene glycol, glycerol and water, to dissolve or suspend the active pharmaceutical ingredient; wherein the parenteral abuse resistant liquid does not comprise a hydrogelling agent; the capsule releases more than 80% of the active pharmaceutical ingredient within the gastrointestinal tract within 30 minutes of administration, all weight percentages being based on a total weight of the parenteral abuse resistant liquid.

2. The immediate release parenteral abuse resistant capsule of claim 1 , wherein a mixture of about 250 to about 1000 milligrams of the abuse resistant liquid with 5 milliliters of water at the mixture's boiling point forms a viscous phase, wherein about 33% or less of the pharmaceutically active ingredient can be recovered from the viscous phase drawn up into a 25 millimeter needle having an inner diameter of 0.60 millimeters.

3. The immediate release parenteral abuse resistant capsule of claim 1 , wherein the surfactant is selected from sorbitanmonolaurate, sorbitanmonooleate, Vitamin E-polyethylenglycol-succinate, and caprylocaproyl macrogol-8 glycerides.

4. The immediate release parenteral abuse resistant capsule of claim 1 , further comprising
(e) a stabilizer.

5. The immediate release parenteral abuse resistant capsule of claim 4 , wherein the stabilizer is selected from the group consisting of colloidal anhydrous silica, hard fat and a glycerol ester of long chain fatty acid.

6. The immediate release parenteral abuse resistant capsule of claim 5 , wherein the stabilizer is colloidal anhydrous silica.

7. The immediate release parenteral abuse resistant capsule of claim 1 , wherein the hydrophilic carrier is macrogol 600 or water.

8. The immediate release parenteral abuse resistant capsule of claim 4 , wherein the stabilizer is hard fat or a glycerol ester of long chain fatty acids.

9. The immediate release parenteral abuse resistant capsule of claim 4 comprising
(i) 40 to 60 wt % macrogol 600;
(ii) 15 to 25 wt % caprylocaproylmacrogol-8 glycerides;
(iii) 3 to 10 wt % colloidal anhydrous silica;
(iv) 3 to 6 wt % glycerol;
(v) 0.5 to 10 wt % water; and
(vi) 2 to 20 wt % ion exchange resin

wherein the weight percentages are calculated with respect to the weight of the parenteral abuse resistant liquid.

10. The immediate release parenteral abuse resistant capsule of claim 1 , wherein the active pharmaceutical ingredient is selected from the group consisting of N-{1-[2-(4-ethyl-5-oxo-2-tetrazolin-1-yl)ethyl]-4-methoxymethyl-4-piperidyl}propionanilide; alfentanil; 5,5-diallylbarbituric acid; allobarbital; allylprodine; alphaprodine; 8-chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]-benzodiazepine; alprazolam; 2-diethylaminopropiophenone; amfepramone, (±)-amethylphenethylamine; amphetamine; 2-(α-methylphenethylamino)-2-phenylacetonitrile; amphetaminil; 5-ethyl-5-isopentylbarbituric acid; amobarbital; anileridine; apocodeine; 5,5-diethylbarbituric acid; barbital; benzylmorphine; bezitramide; 7-bromo-5-(2-pyridyl)-1H-1,4-benzodiazepine-2(3H)-one; bromazepam; 2-bromo-4-(2-chlorophenyl)-9-methyl-1-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine; brotizolam, 17-cyclopropylmethyl-4,5a-epoxy-7a[(S)-1-hydroxy-1,2,2-trimethyl-propyl]-6-methoxy-6,14-endo-ethanomorphinan-3-ol; buprenorphine; 5-butyl-5-ethylbarbituric acid; butobarbital; butorphanol; (7-chloro-1,3-dihydro-1-methyl-2-oxo-5-phenyl-2H-1,4-benzodiazepin-3-yl)dimethylcarbamate; camazepam; (1S,2S)-2-amino-1-phenyl-1-propanol; cathine; d-norpseudoephedrine; 7-chloro-N-methyl-5-phenyl-3H-1,4-benzodiazepin-2-yl-amine 4-oxide; chlordiazepoxide, 7-chloro-1-methyl-5-phenyl-1H-1,5-benzodi-azepine-2,4(3H,5H)-dione; clobazam, 5-(2-chlorophenyl)-7-nitro-1H-1,4-benz-odiazepin-2(3H)-one; clonazepam; clonitazene; 7-chloro-2,3-dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3-carboxylic acid; clorazepate; 5-(2-chlorophenyl)-7-ethyl-1-methyl-1H-thieno[2,3-e][1,4]diazepin-2(3H)-one; clotiazepam; 10-chloro-11b-(2-chlorophenyl)-2,3,7,11b-tetrahydrooxazol-o[3,2-d][1,4]benzodiazepin-6(5H)-one; cloxazolam; (−)-methyl-[3β-benzoyloxy-2β(1αH,5αH)-tropane carboxylate]; cocaine; (5α,6α)-7,8-didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol; 4,5α-epoxy-3-methoxy-17-methyl-7-morphinen-6α-ol; codeine; 5-(1-cyclohexenyl)-5-ethyl barbituric acid; cyclobarbital; cyclorphan; cyprenorphine; 7-chloro-5-(2-chloropheny-1)-1H-1,4-benzodiazepin-2(3H)-one; delorazepam; desomorphine; dextromoramide; (+)-(1-benzyl-3-dimethylamino-2-methyl-1-phenylpropyl)propionate; dextropropoxyphene; dezocine; diampromide; diamorphone; 7-chloro-1-methyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-on; diazepam; 4,5α-epoxy-3-methoxy-17-methyl-6α-morphinanol; dihydrocodeine; 4,5α-epoxy-17-methyl-3,6a-morphinandiol; dihydromorphine; dimenoxadol; dimephetamol; dimethylthiambutene; dioxaphetyl butyrate; dipipanone; (6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol; dronabinol; eptazocine; 8-chloro-6-phenyl-4H-[1,2,4]-triazolo[4,3-(a)][1,4]benzodiazepine; estazolam; ethoheptazine; ethylmethylthiambutene; ethyl[7-chloro-5-(2-fluorophenyl)-2,3-dihydro-2-oxo-1H-1,4-benzodiazepine-3-carboxylate]; ethyl loflazepate; 4,5α-epoxy-3-ethoxy-17-methyl-7-morphinen-6α-ol; ethylmorphine; etonitazene; 4,5α-epoxy-7α-(1-hydroxy-1-methylbutyl)-6-methoxy-17-methyl-6,14-endo-etheno-morphinan-3-ol; etorphine; N-ethyl-3-phenyl-8,9,10-trinorbornan-2-ylamine; fencamfamine; 7-[2-(α-methylphenethylamino)ethyl]-theophylline; fenethylline; 3-(α-methylphenethylamino)propionitrile; fenproporex; N-(1-phenethyl-4-piperidyl)propionanilide; fentanyl; 7-chloro-5-(2-fluorophenyl)-1-methyl-1H-1,4-benzodiazepin-2(3H)-one; fludiazepam; 5-(2-fluorophenyl)-1-methyl-7-nitro-1H-1,4-benzodiazepin-2(3H)-one; flunitrazepam; 7-chloro-1-(2-diethylaminoethyl)-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2(3H)-one; flurazepam; 7-chloro-5-phenyl-1-(2,2,2-trifluoroethyl)-1H-1,4-benzodiazepin-2(3H)-one; halazepam; 10-bromo-11b-(2-fluorophenyl)-2,3,7,11b-tetrahydro[1,3]oxazolyl[3,2-d][1,4]benzodiazepin-6(5H)-one; haloxazolam; heroin; 4,5α-epoxy-3-methoxy-17-methyl-6-morphinanone; hydrocodone; 4,5α-epoxy-3-hydroxy-17-methyl-6-morphinanone; hydromorphone; hydroxypethidine; isomethadone; hydroxymethylmorphinan; 11-chloro-8,12b-dihydro-2,8-dimethyl-12b-phenyl-4H-[1,3]oxazino[3,2d][1,4]benzodiazepine-4,7(6H)-dione; ketazolam; 1-[4-(3-hydroxyphenyl)-1-methyl-4-piperidyl]-1-propanone; ketobemidone; (3S,6S)-6-dimethylamino-4,4-diphenylheptan-3-yl acetate; levacetylmethadol; LAAM; (−)-6-dimethylamino-4,4-diphenol-3-heptanone; levome

Assignees

• Scherer Technologies Llc R P

Inventors

• Wengner Simone

Classifications

• A61K31/137

  Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone} · CPC title

• A61P25/36

  Opioid-abuse · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title

• A61K9/08

  Solutions {(composition of solutions A61K47/00)} · CPC title

• A61K31/485

  Morphinan derivatives, e.g. morphine, codeine · CPC title