ABUSE-DETERRENT COMPOSITIONS
Described herein are abuse deterrent controlled release oral pharmaceutical compositions comprising and methods for making the same. In particular, an abuse deterrent controlled release oral pharmaceutical composition comprising a soft capsule and an abuse deterrent controlled release matrix comprising an active pharmaceutical ingredient are described.
1 . An oral pharmaceutical composition comprising:
a soft gelatin capsule shell encapsulating a tamper resistant, homogenous, viscous, yet flowable matrix consisting essentially of:
(a) hydrophobic matrix phase comprising:
one or more lipophilic vehicles consisting of about 25% to about 85% of the flowable matrix mass; and
optionally one or more semisolid lipids consisting of 0% to about 10% of the flowable matrix;
(b) a hydrophilic phase comprising:
one or more hydrophilic polymers consisting of about 8% to about 50% of the flowable matrix mass;
one or more hydrophilic vehicles consisting of about 2% to about 60% of the flowable matrix mass; and
one or more organogelators consisting of about 0.5% to about 25% of the flowable matrix mass; and
(c) one or more active pharmaceutical ingredients dissolved in the flowable matrix consisting of about 1% to about 35% of the flowable matrix mass.
2 . The composition of claim 1 , wherein the ratio of the hydrophobic matrix phase to the hydrophilic matrix phase is about 0.7:1 to about 10:1.
3 . The composition of claim 1 , wherein the lipophilic vehicle comprises one or more of olive oil, soybean oil, sunflower oil, canola oil, palmitoleic acid, oleic acid, myristoleic acid, linoleic acid, arachidonic acid, paraffin oil, or mineral oil.
4 . The composition of claim 1 , wherein the semisolid lipid or lipophilic vehicle comprises one or more of polyethylene glycol glyceride ester, paraffin wax, carnauba wax, or bee's wax.
5 . The composition of claim 1 , wherein the semisolid lipid or lipophilic vehicle comprises one or more of carnauba wax or bee's wax.
6 . The composition of claim 1 , wherein the hydrophilic polymer comprises or more of methylcellulose, hydroxypropylmethyl cellulose, a mixture of hydroxypropylmethyl cellulose and methylcellulose, polymethylmethacrylate, polyvinyl or pyrrolidone.
7 . The composition of claim 1 , wherein the hydrophilic vehicle comprises one or more of propylene glycol, or polyethylene glycols having a molecular weight of about 200 to about 8,000.
8 . The composition of claim 1 , wherein the organogelator comprises one or more of ethyl cellulose, 12-hydroxyoctadecanoic acid, 1,3:2,4-di-O-benzylidene-D-sorbitol, 2,3-bis-n-decyloxyanthracene, alkyl perfluoroalkanamides, sorbitan monostearate.
10 . The composition of claim 1 , wherein composition further comprises one or more antioxidants.
11 . The composition of claim 10 , wherein the antioxidant comprises about 0.05% to about 0.5% of the total matrix mass.
12 . The composition of claim 10 , wherein the antioxidant comprises one or more of alpha-tocopherol, beta-tocopherol, gamma-tocopherol, delta-tocopherol, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), citric acid, ascorbic acid, carnosic acid, carnosol, rosmanol, epirosmanol, isorosmanol, methyl carnosate, rosmarinic acid, eugenol, eugenyl acetate, clove bud extract, methanolic extract, epigallocatechin gallate, epicatechin gallate, epigallocatechin, or epicatechin.
13 . The composition of claim 1 , wherein the composition further comprises one or more disintegrants.
14 . The composition of claim 13 , wherein the disintegrant comprises about 0.01% to about 5% of the total matrix mass.
14 . The composition of claim 12 , wherein the disintegrant comprises one or more of crospovidone, crosslinked sodium carboxymethyl cellulose (croscarmellose sodium) carboxymethyl cellulose calcium, cysteine HCl, sodium starch glycolate, cellulose, calcium silicate, silicon dioxide, alginic acid, sodium alginate, citric acid, microcrystalline cellulose, polyoxy stearate, sodium croscarmellose, or sodium lauryl sulfate.
15 . The composition of claim 1 , wherein the ratio of the active pharmaceutical ingredient percent mass to the flowable matrix percent mass is about 1:100 to about 1:3.
16 . The composition of claim 1 , wherein the active pharmaceutical ingredient comprises one or more of hydrocodone, morphine, morphine analogues, or morphine antagonists, tapentadol, codeine, morphine, methadone, fentanyl and analogs, hydrocodone hydrochloride, hydrocodone bitartrate, hydromorphone, oxymorphone, oxycodone, meperidine, propoxyphene, flunitrazepam, barbiturates, amytal, nembutal, seconal, phenobarbital; benzodiazepines, zolpidem, zaleplon, eszopiclone, amphetamines, or methylphenidate.