SUSTAINED RELEASE FORMULATION OF NALTREXONE
A sustained-release oral dosage form of naltrexone or a pharmaceutically acceptable salt thereof is provided. The oral dosage form may be administered with another compound. Administration of the oral dosage form may reduce a side effect, which may be a side effect at least partially attributable to a weight-loss treatment. The oral dosage form may be administered to treat a weight-loss condition.
1 . An oral dosage form, comprising a sustained-release naltrexone formulation that is formulated to provide a reduction in at least one adverse effect, wherein the adverse effect is associated with co-administration of an immediate-release naltrexone formulation and a second compound.
2 . The oral dosage form of claim 1 , wherein the second compound comprises a monoamine reuptake inhibitor.
3 . The oral dosage form of claim 1 , wherein the second compound comprises bupropion or a pharmaceutically acceptable salt thereof.
4 . The oral dosage form of claim 1 , wherein the second compound comprises fluoxetine or a pharmaceutically acceptable salt thereof.
5 . The oral dosage form of claim 1 , wherein the reduction in the at least one adverse effect comprises a reduction in one or more of the severity, the duration, or the probability of experiencing the at least one adverse effect.
6 . The oral dosage form of claim 1 , wherein the at least one adverse effect comprises nausea.
7 . The oral dosage form of claim 1 , wherein the sustained-release naltrexone formulation is in a unit dosage form comprising an amount of naltrexone in the range of from about 4 mg to about 50 mg.
8 . The oral dosage form of claim 1 , wherein the sustained-release naltrexone formulation is in a unit dosage form comprising an amount of naltrexone in the range of from about 10 mg to about 25 mg.
9 . The oral dosage form of claim 1 , wherein the sustained-release naltrexone formulation is in a unit dosage form comprising about 4 mg, about 8 mg, about 12 mg, about 16 mg, about 32 mg or about 48 mg of naltrexone.
10 . The oral dosage form of claim 1 , wherein the sustained-release naltrexone formulation is in a unit dosage form suitable for administration one or more times per day.
11 . The oral dosage form of claim 10 , wherein the unit dosage form is suitable for administration two or more times per day.
12 . The oral dosage form of claim 1 , wherein the oral dosage form further comprises the second compound.
13 . The oral dosage form of claim 12 , wherein the second compound comprises bupropion or a pharmaceutically acceptable salt thereof.
14 . The oral dosage form of claim 13 , wherein the bupropion or a pharmaceutically acceptable salt thereof is a sustained release formulation.
15 . The oral dosage form of claim 14 , wherein the sustained-release naltrexone formulation is in a unit dosage form; wherein the unit dosage form comprises naltrexone in an amount of about 4 mg, about 8 mg or about 12 mg; and wherein the unit dosage form comprises bupropion or a pharmaceutically acceptable salt thereof in an amount of about 90 mg.
16 . The oral dosage form of claim 12 , wherein the second compound comprises fluoxetine or a pharmaceutically acceptable salt thereof.
17 . The oral dosage form of claim 1 , wherein the oral dosage form comprises an amount of a sustained-release carrier composition that is effective to provide, after administration, an in vivo plasma concentration profile comprising at least one selected from:
(a) a naltrexone C max that is about 80% or less of the naltrexone C max of REVIA™ immediate-release naltrexone hydrochloride, and a naltrexone AUC last that is in the range of about 80% to about 125% of the naltrexone AUC last of REVIA™ immediate-release naltrexone hydrochloride; and
(b) a 6-beta naltrexol C max that is about 80% or less of the 6-beta naltrexol C max of REVIA™ immediate-release naltrexone hydrochloride, and a 6-beta naltrexol AUC last that is in the range of about 80% to about 125% of the 6-beta naltrexol AUC last of REVIA™ immediate-release naltrexone hydrochloride.
18 . The oral dosage form of claim 17 , wherein said sustained-release carrier composition comprises at least one of hydroxypropylmethyl cellulose, polyoxyethylene, polyacrylate, a copolymer of acrylate and methacrylate, a methacrylate polymer, a copolymer of acrylate and methacrylate, a copolymer of acrylate and methacrylate with ammonium group, a copolymer of maleic anhydride and methyl vinyl ether, hydroxy propyl ethyl cellulose, hydroxy propyl cellulose, hydroxy ethyl cellulose, methyl cellulose, hydroxymethyl methacrylate, maltodextrin, natural gum and xanthan gum.
19 . The oral dosage form of claim 17 , wherein said sustained-release carrier composition comprises at least one of hydroxypropylmethylcellulose and polyoxyethylene.
20 . An oral unit dosage form, comprising a sustained-release naltrexone formulation that is effective to provide, after administration, an in vivo plasma concentration profile comprising at least one selected from:
(a) a naltrexone C max that is about 80% or less of the naltrexone C max of REVIA™ immediate-release naltrexone hydrochloride, and a naltrexone AUC last that is in the range of about 80% to about 125% of the naltrexone AUC last of REVIA™ immediate-release naltrexone hydrochloride; and
(b) a 6-beta naltrexol C max that is about 80% or less of the 6-beta naltrexol C max of REVIA™ immediate-release naltrexone hydrochloride, and a 6-beta naltrexol AUC last that is in the range of about 80% to about 125% of the 6-beta naltrexol AUC last of REVIA™ immediate-release naltrexone hydrochloride.
21 . The oral unit dosage form of claim 20 , comprising an amount of naltrexone in the range of from about 4 mg to about 50 mg.
22 . The oral unit dosage form of claim 20 , comprising an amount of naltrexone in the range of from about 10 mg to about 25 mg.
23 . The oral unit dosage form of claim 20 , comprising about 4 mg, about 8 mg, about 12 mg, about 16 mg, about 32 mg or about 48 mg of naltrexone.
24 . An oral dosage form, comprising naltrexone or a pharmaceutically acceptable salt thereof and a sustained-release carrier composition, wherein said oral dosage form provides an in vitro release rate of the naltrexone or pharmaceutically acceptable salt thereof of less than about 80% in about 1 hour.
25 . The oral dosage form of claim 24 , wherein said in vitro release rate is less than about 70% in about 1 hour.
26 . The oral dosage form of claim 24 , wherein said sustained-release carrier composition comprises at least one of hydroxypropylmethyl cellulose, polyoxyethylene, polyacrylate, a copolymer of acrylate and methacrylate, a methacrylate polymer, a copolymer of acrylate and methacrylate, a copolymer of acrylate and methacrylate with ammonium group, a copolymer of maleic anhydride and methyl vinyl ether, hydroxy propyl ethyl cellulose, hydroxy propyl cellulose, hydroxy ethyl cellulose, methyl cellulose, hydroxymethyl methacrylate, maltodextrin, natural gum and xanthan gum.
27 . The oral dosage form of claim 24 , wherein said sustained-release carrier composition comprises at least one of hydroxypropylmethylcellulose and polyoxyethylene.
28 . The oral dosage form of claim 24 , wherein the naltrexone salt comprises naltrexone hydrochloride.
29 . A method of administering naltrexone, comprising administering the oral dosage form of claim 1 to a subject.
30 . The method of claim 29 , comprising administering the oral dosage form to the subject in a manner that is effective to cause weight loss and/or inhibit weight gain.
31 . The method of claim 29 , further comprising administering a second compound to the subject.
32 . The method of claim 31 , wherein the second compound comprises bupropion or a pharmaceutically acceptable salt thereof.
33 . The method of claim 32 , wherein the sustained-release naltrexone formulation is in a unit dosage form; wherein the unit dosage form comprises naltrexone in an amount of about 4 mg, about 8 mg or about 12 mg; and wherein the unit dosage form comprises bupropion or a pharmaceutically acceptable salt thereof in an amount of about 90 mg.
34 . The method of claim 31 , wherein the second compound comprises fluoxetine or a pharmaceutically acceptable salt thereof.
35 . A method of administering naltrexone, comprising administering a sustained-release naltrexone formulation to a subject in an amount that is effective to provide an in vivo plasma concentration profile comprising at least one selected from:
(a) a naltrexone C max that is about 80% or less of the naltrexone C max of REVIA™ immediate-release naltrexone hydrochloride, and a naltrexone AUC last that is in the range of about 80% to about 125% of the naltrexone AUC last of REVIA™ immediate-release naltrexone hydrochloride; and
(b) a 6-beta naltrexol C max that is about 80% or less of the 6-beta naltrexol C max of REVIA™ immediate-release naltrexone hydrochloride, and a 6-beta naltrexol AUC last that is in the range of about 80% to about 125% of the 6-beta naltrexol AUC last of REVIA™ immediate-release naltrexone hydrochloride.
36 . The method of claim 35 , comprising administering the sustained-release naltrexone formulation to the subject in a manner that is effective to cause weight loss and/or inhibit weight gain.
37 . The method of claim 35 , further comprising administering a second compound to the subject.
38 . The method of claim 37 , wherein the second compound comprises a monoamine reuptake inhibitor.
39 . The method of claim 38 , wherein administration of the monoamine reuptake inhibitor in combination with an immediate-release form of naltrexone results in at least one adverse effect that is reduced by the administration of the sustained-release naltrexone formulation.
40 . The method of claim 38 , wherein the monoamine reuptake inhibitor comprises bupropion or a pharmaceutically acceptable salt thereof.
41 . The method of claim 40 , wherein the sustained-release naltrexone formulation is in a unit dosage form; wherein the unit dosage form comprises naltrexone in an amount of about 4 mg, about 8 mg or about 12 mg; and wherein the unit dosage form comprises bupropion or a pharmaceutically acceptable salt thereof in an amount of about 90 mg.
42 . The method of claim 38 , wherein the monoamine reuptake inhibitor comprises fluoxetine or a pharmaceutically acceptable salt thereof.