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US 2005/0238718 A1Published application
Modified-release tablet of bupropion hydrochloride
OwnerWerner Oberegger, Okponanabofa Eradiri +2inventors
InventorsWerner Oberegger, Okponanabofa Eradiri, Fang Zhou, Paul Maes
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Abstract
A modified-release tablet of bupropion hydrochloride comprising (i) a core comprising an effective amount of bupropion hydrochloride, a binder, a lubricant; and (ii) a control releasing coat surrounding said core; and (iii) a moisture barrier surrounding said control releasing coat, wherein the modified-release tablet is bioequivalent to Wellbutrin® or Zyban®/Wellbutrin® SR tablets.
Claims154
A modified-release tablet comprising:
- (i) a core comprising an effective amount of a pharmaceutically acceptable salt of bupropion, and conventional excipients;
- (ii) a first control-releasing coat surrounding said core;
- and
- (iii) a moisture barrier surrounding said first control-releasing coat,
- wherein the modified-release tablet is bioequivalent and exhibits a dissolution profile such that after about 2 hours no more than about 20% of the bupropion content is released, after about 4 hours about 15% to about 45% of the bupropion content is released, after about 8 hours about 40% to about 90% of the bupropion content is released and after about 16 hours no less than about 80% of the bupropion content is released.
2 more elements
A modified-release tablet comprising:
- (i) a core comprising an effective amount of a pharmaceutically acceptable salt of bupropion, and conventional excipients;
- (ii) a control-releasing coat surrounding said core, said control-releasing coat comprising a water-insoluble, water-permeable film-forming polymer, a plasticizer and a water-soluble polymer;
- and
- (iii) a moisture barrier surrounding said control-releasing coat, wherein said moisture barrier does not function as an enteric coating as defined by a USP test which requires for an enteric layer-coated tablet, when placed in 0.1N HCl for one hour, that the total amount of the drug released from the core does not exceed 10% and not less than 75% of the drug is released at 45 minutes in pH 6.8 buffer,
- wherein the modified-release tablet is bioequivalent and exhibits a dissolution profile such that after about 2 hours no more than about 20% of the bupropion content is released, after about 4 hours about 15% to about 45% of the bupropion content is released, after about 8 hours about 40% to about 90% of the bupropion content is released and after about 16 hours no less than about 80% of the bupropion content is released.
2 more elements
A modified-release tablet comprising:
- (i) a core comprising an effective amount of bupropion hydrochloride, polyvinyl alcohol, glyceryl behenate, wherein said bupropion hydrochloride is present at least at about 94% by weight of the core dry weight, said polyvinyl alcohol is present at about 3% by weight of the core dry weight, and said glyceryl behenate is present at about 3% by weight of each core dry weight;
- (ii) a control-releasing coat surrounding said core, said control-releasing coat comprising ethyl cellulose grade PR 100, polyethylene glycol 1450, and polyvinylpyrrolidone, wherein said ethyl cellulose grade PR 100 is present from about 45% to about 50% by weight of the control-releasing coating dry weight, said polyethylene glycol 1450 is present at about 12% by weight of the control-releasing coating dry weight, and said polyvinylpyrrolidone is present from about 25% to about 50% of the control-releasing coat dry weight, wherein the amount of said control-releasing coat applied is from about 9% to about 15% by weight of the dry tablet core;
- and
- (iii) a moisture barrier surrounding said control-releasing coat, said moisture barrier comprising methacrylic acid copolymer, polyethylene glycol 1450, triethyl citrate and silicon dioxide, wherein said methacrylic acid copolymer is present at about 66% by weight of said moisture barrier dry weight, said polyethylene glycol 1450 and triethyl citrate is present at about 10% by weight of said moisture barrier dry weight in a proportion of 1 part triethyl citrate to 2 parts polyethylene glycol 1450, and said silicon dioxide is present at about 25% by weight of said moisture barrier dry weight, wherein the amount of the said moisture barrier applied is no more than about 2.5% of the tablet dry weight;
- wherein said modified-release tablet is bioequivalent and exhibits a dissolution profile such that after about 2 hours about 5% of the bupropion hydrochloride content is released, after about 4 hours, about 32% of the bupropion hydrochloride content is released, after about 8 hours, about 74% of the bupropion hydrochloride content is released and after about 16 hours no less than about 99% of the bupropion hydrochloride content is released.
2 more elements
A modified-release tablet comprising:
- (i) a core comprising an effective amount of bupropion hydrochloride and conventional excipients;
- (ii) a control-releasing coat surrounding said core, said control-releasing coat comprising a water-insoluble, water-permeable film-forming polymer, a plasticizer and a water-soluble polymer;
- and
- (iii) a moisture barrier surrounding said control-releasing coat, said moisture barrier comprising, methacrylic acid copolymer, polyethylene glycol 1450, triethyl citrate and silicon dioxide, wherein said methacrylic acid copolymer is present at about 66% by weight of said moisture barrier dry weight, said polyethylene glycol 1450 and triethyl citrate is present at about 10% by weight of said moisture barrier dry weight in a proportion of about 1 part triethyl citrate to about 2 parts polyethylene glycol 1450 and said silicon dioxide is present at about 25% by weight of said moisture barrier dry weight, wherein the amount of the said moisture barrier applied is no more than about 2.5% of the tablet dry weight,
- wherein said modified-release tablet is bioequivalent and wherein said modified-release tablet when administered to a patient in need of such administration in the fasted state provides a Cmax of bupropion in the blood plasma at between about 3 hours and about 8 hours (Tmax) after administration of the modified-release tablet.
2 more elements
A modified-release tablet comprising:
- (i) a core comprising an effective amount of bupropion hydrochloride and conventional excipients;
- (ii) a control-releasing coat surrounding said core, said control-releasing coat comprising a water-insoluble water-permeable film-forming polymer, a plasticizer and a water-soluble polymer;
- and
- (iii) a moisture barrier surrounding said control-releasing coat, said moisture barrier comprising, methacrylic acid copolymer, polyethylene glycol 1450, triethyl citrate and silicon dioxide, wherein said methacrylic acid copolymer is present at about 66% by weight of said moisture barrier dry weight, said polyethylene glycol 1450 and triethyl citrate is present at about 10% by weight of said moisture barrier dry weight in a proportion of about 1 part triethyl citrate to about 2 parts polyethylene glycol 1450 and said silicon dioxide is present at about 25% by weight of said moisture barrier dry weight wherein the amount of the said moisture barrier applied is no more than about 2.5% of the tablet dry weight,
- wherein said modified-release tablet is bioequivalent and wherein said modified-release tablet when administered to a patient in need of such administration in the fasted state provides a Cmax of bupropion in the blood plasma at about 5 hours (Tmax) after administration of the modified-release tablet.
2 more elements
A modified-release tablet comprising:
- (i) a core comprising an effective amount of bupropion hydrochloride and conventional excipients;
- (ii) a control-releasing coat surrounding said core, said control-releasing coat comprising a water-insoluble water-permeable film-forming polymer, a plasticizer and a water-soluble polymer;
- and
- (iii) a moisture barrier surrounding said control-releasing coat, said moisture barrier comprising, methacrylic acid copolymer, polyethylene glycol 1450, triethyl citrate and silicon dioxide, wherein said methacrylic acid copolymer is present at about 66% by weight of said moisture barrier dry weight, said polyethylene glycol 1450 and triethyl citrate is present at about 10% by weight of said moisture barrier dry weight in a proportion of about 1 part triethyl citrate to about 2 parts polyethylene glycol 1450 and said silicon dioxide is present at about 25% by weight of said moisture barrier dry weight wherein the amount of the said moisture barrier applied is no more than about 2.5% of the tablet dry weight,
- wherein said modified-release tablet is bioequivalent and wherein said modified-release tablet when administered to a patient in need of such administration in the fasted state provides a Cmax of bupropion ranging from about 60 ng/ml to about 280 ng/ml in the blood plasma at about 5 hours (Tmax) after administration of a once daily 300 mg dose of said modified-release bupropion hydrochloride tablet or a 2×150 mg dose once daily of said modified-release bupropion hydrochloride tablet.
2 more elements
A modified-release tablet comprising:
- (i) a core comprising an effective amount of bupropion hydrochloride and conventional excipients;
- (ii) a control-releasing coat surrounding said core, said control-releasing coat comprising a water-insoluble water-permeable film-forming polymer, a plasticizer and a water-soluble polymer;
- and
- (iii) a moisture barrier surrounding said control-releasing coat, said moisture barrier comprising, methacrylic acid copolymer, polyethylene glycol 1450, triethyl citrate and silicon dioxide, wherein said methacrylic acid copolymer is present at about 66% by weight of said moisture barrier dry weight, said polyethylene glycol 1450 and triethyl citrate is present at about 10% by weight of said moisture barrier dry weight in a proportion of about 1 part triethyl citrate to about 2 parts polyethylene glycol 1450 and said silicon dioxide is present at about 25% by weight of said moisture barrier dry weight wherein the amount of the said moisture barrier applied is no more than about 2.5% of the tablet dry weight,
- wherein said modified-release tablet is bioequivalent and wherein said modified-release tablet when administered to a patient in need of such administration in the fasted state exhibits a blood plasma concentration profile for bupropion as shown in FIG. 3A after administration of a once daily 300 mg dose of said modified-release bupropion hydrochloride tablet or a 2×150 mg dose once daily of said modified-release bupropion hydrochloride tablet.
2 more elements
A modified-release tablet comprising:
- (i) a core comprising an effective amount of bupropion hydrochloride and conventional excipients;
- (ii) a control-releasing coat surrounding said core, said control-releasing coat comprising a water-insoluble, water-permeable film-forming polymer, a plasticizer and a water-soluble polymer, and
- (iii) a moisture barrier surrounding said control-releasing coat, said moisture barrier comprising, methacrylic acid copolymer, polyethylene glycol 1450, triethyl citrate and silicon dioxide, wherein said methacrylic acid copolymer is present at about 66% by weight of said moisture barrier dry weight, said polyethylene glycol 1450 and triethyl citrate is present at about 10% by weight of said moisture barrier dry weight in a proportion of about 1 part triethyl citrate to about 2 parts polyethylene glycol 1450 and said silicon dioxide is present at about 25% by weight of said moisture barrier dry weight wherein the amount of the said moisture barrier applied is no more than about 2.5% of the tablet dry weight,
- wherein said modified-release tablet is bioequivalent and wherein said modified-release tablet when administered to a patient in need of such administration in the fasted state exhibits an AUC(0-t) for bupropion from about 800 ng.hr/ml to about 2850 ng.hr/ml after administration of a once daily 300 mg dose of said modified-release bupropion hydrochloride tablet or a 2×150 mg dose once daily of said modified-release bupropion hydrochloride tablet.
1 more element
A modified-release tablet comprising:
- (i) a core comprising an effective amount of bupropion hydrochloride and conventional excipients;
- (ii) a control-releasing coat surrounding said core, said control-releasing coat comprising a water-insoluble water-permeable film-forming polymer, a plasticizer and a water-soluble polymer;
- and
- (iii) a moisture barrier surrounding said control-releasing coat, said moisture barrier comprising, methacrylic acid copolymer, polyethylene glycol 1450, triethyl citrate and silicon dioxide, wherein said methacrylic acid copolymer is present at about 66% by weight of said moisture barrier dry weight, said polyethylene glycol 1450 and triethyl citrate is present at about 10% by weight of said moisture barrier dry weight in a proportion of about 1 part triethyl citrate to about 2 parts polyethylene glycol 1450 and said silicon dioxide is present at about 25% by weight of said moisture barrier dry weight, wherein the amount of the said moisture barrier applied is no more than about 2.5% of the tablet dry weight,
- wherein said modified-release tablet is bioequivalent and wherein said modified-release tablet when administered to a patient in need of such administration in the fasted state exhibits an AUC(0-inf) for bupropion from about 840 ng.hr/ml to about 3000 ng.hr/ml after administration of a once daily 300 mg dose of said modified-release bupropion hydrochloride tablet or a 2×150 mg dose once daily of said modified-release bupropion hydrochloride tablet.
2 more elements
A modified-release tablet comprising:
- (i) a core comprising an effective amount of bupropion hydrochloride and conventional excipients;
- (ii) a control-releasing coat surrounding said core, said control-releasing coat comprising a water-insoluble water-permeable film-forming polymer, a plasticizer and a water-soluble polymer, and
- (iii) a moisture barrier surrounding said control-releasing coat, said moisture barrier comprising, methacrylic acid copolymer, polyethylene glycol 1450, triethyl citrate and silicon dioxide, wherein said methacrylic acid copolymer is present at about 66% by weight of said moisture barrier dry weight, said polyethylene glycol 1450 and triethyl citrate is present at about 10% by weight of said moisture barrier dry weight in a proportion of about 1 part triethyl citrate to about 2 parts polyethylene glycol 1450 and said silicon dioxide is present at about 25% by weight of said moisture barrier dry weight, wherein the amount of the said moisture barrier applied is no more than about 2.5% of the tablet dry weight,
- wherein said modified-release tablet when administered as a 2×150 mg dose once daily or a 300 mg dose once daily to a patient in need of such administration in the fasted state is bioequivalent to Zyban®Wellbutrin® SR.
1 more element
A modified-release tablet comprising:
- (i) a core comprising an effective amount of bupropion hydrochloride and conventional excipients;
- (ii) a control-releasing coat surrounding said core, said control-releasing coat comprising a water-insoluble water-permeable film-forming polymer, a plasticizer and a water-soluble polymer, and
- (iii) a moisture barrier surrounding said control-releasing coat, said moisture barrier comprising, methacrylic acid copolymer, polyethylene glycol 1450, triethyl citrate and silicon dioxide, wherein said methacrylic acid copolymer is present at about 66% by weight of said moisture barrier dry weight, said polyethylene glycol 1450 and triethyl citrate is present at about 10% by weight of said moisture barrier dry weight in a proportion of about 1 part triethyl citrate to about 2 parts polyethylene glycol 1450 and said silicon dioxide is present at about 25% by weight of said moisture barrier dry weight, wherein the amount of the said moisture barrier applied is no more than about 2.5% of the tablet dry weight;
- wherein said modified-release tablet administered as a 2×150 mg dose once daily or a 300 mg dose administered once daily to a patient in need of such administration does not exhibit a food effect.
1 more element
A modified-release tablet comprising:
- (i) a core comprising an effective amount of a pharmaceutically acceptable salt of bupropion hydrochloride and conventional excipients;
- (ii) a control-releasing coat surrounding said core, said control-releasing coat comprising a water-insoluble water-permeable film-forming polymer, a plasticizer and a water-soluble polymer, and
- (iii) a moisture barrier surrounding said control-releasing coat, said moisture barrier comprising, methacrylic acid copolymer, polyethylene glycol 1450, triethyl citrate and silicon dioxide, wherein said methacrylic acid copolymer is present at about 66% by weight of said moisture barrier dry weight, said polyethylene glycol 1450 and triethyl citrate is present at about 10% by weight of said moisture barrier dry weight in a proportion of about 1 part triethyl citrate to about 2 parts polyethylene glycol 1450 and said silicon dioxide is present at about 25% by weight of said moisture barrier dry weight, wherein the amount of the said moisture barrier applied is no more than about 2.5% of the tablet dry weight;
- wherein said modified-release tablet is bioequivalent and wherein a single dose of said modified-release tablet when administered to a patient in need of such administration in the fasted or fed state exhibits mean plasma concentration-time curves as shown in FIG. 4A.
1 more element
A modified-release tablet comprising:
- (i) a core comprising an effective amount of bupropion hydrochloride and conventional excipients;
- (ii) a control-releasing coat surrounding said core, said control-releasing coat comprising a water-insoluble water-permeable film-forming polymer, a plasticizer and a water-soluble polymer, and
- (iii) a moisture barrier surrounding said control-releasing coat, said moisture barrier comprising, methacrylic acid copolymer, polyethylene glycol 1450, triethyl citrate and silicon dioxide, wherein said methacrylic acid copolymer is present at about 66% by weight of said moisture barrier dry weight, said polyethylene glycol 1450 and triethyl citrate is present at about 10% by weight of said moisture barrier dry weight in a proportion of about 1 part triethyl citrate to about 2 parts polyethylene glycol 1450 and said silicon dioxide is present at about 25% by weight of said moisture barrier dry weight, wherein the amount of the said moisture barrier applied is no more than about 2.5% of the tablet dry weight,
- wherein said modified-release tablet when administered as a 300 mg dose once daily to a patient in need of such administration in the fasted state is bioequivalent to Wellbutrin® tablets administered 1×300 mg (t.i.d) at steady state.
1 more element
A modified-release tablet comprising:
- (i) a core comprising an effective amount of bupropion hydrochloride and conventional excipients;
- (ii) a control-releasing coat surrounding said core, said control-releasing coat comprising a water-insoluble water-permeable film-forming polymer, a plasticizer and a water-soluble polymer, and
- (iii) a moisture barrier surrounding said control-releasing coat, said moisture barrier comprising, methacrylic acid copolymer, polyethylene glycol 1450, triethyl citrate and silicon dioxide, wherein said methacrylic acid copolymer is present at about 66% by weight of said moisture barrier dry weight, said polyethylene glycol 1450 and triethyl citrate is present at about 10% by weight of said moisture barrier dry weight in a proportion of about 1 part triethyl citrate to about 2 parts polyethylene glycol 1450 and said silicon dioxide is present at about 25% by weight of said moisture barrier dry weight, wherein the amount of the said moisture barrier applied is no more than about 2.5% of the tablet dry weight,
- wherein said modified-release tablet when administered as a 300 mg dose once daily to a patient in need of such administration in the fasted state is bioequivalent to Zyban® administered 1×150 mg twice daily (b.i.d.) at steady state.
1 more element
A modified-release tablet comprising:
- (i) a core comprising an effective amount of bupropion hydrochloride and conventional excipients;
- (ii) a control-releasing coat surrounding said core, said control-releasing coat comprising a water-insoluble water-permeable film-forming polymer, a plasticizer and a water-soluble polymer, and
- (iii) a moisture barrier surrounding said control-releasing coat, said moisture barrier comprising, methacrylic acid copolymer, polyethylene glycol 1450, triethyl citrate and silicon dioxide, wherein said methacrylic acid copolymer is present at about 66% by weight of said moisture barrier dry weight, said polyethylene glycol 1450 and triethyl citrate is present at about 10% by weight of said moisture barrier dry weight in a proportion of about 1 part triethyl citrate to about 2 parts polyethylene glycol 1450 and said silicon dioxide is present at about 25% by weight of said moisture barrier dry weight, wherein the amount of the said moisture barrier applied is no more than about 2.5% of the tablet dry weight,
- wherein the moisture content is no more than about 0.4% in said tablet when stored at 40° C.±2° C./75% RH±5% RH in an open dish after about 10 days.
1 more element
A modified-release tablet comprising:
- (i) a core comprising an effective amount of bupropion hydrochloride and conventional excipients;
- (ii) a control-releasing coat surrounding said core, said control-releasing coat comprising a water-insoluble water-permeable film-forming polymer, a plasticizer and a water-soluble polymer, and
- (iii) a moisture barrier surrounding said control-releasing coat, said moisture barrier comprising, methacrylic acid copolymer, polyethylene glycol 1450, triethyl citrate and silicon dioxide, wherein said methacrylic acid copolymer is present at about 66% by weight of said moisture barrier dry weight, said polyethylene glycol 1450 and triethyl citrate is present at about 10% by weight of said moisture barrier dry weight in a proportion of about 1 part triethyl citrate to about 2 parts polyethylene glycol 1450 and said silicon dioxide is present at about 25% by weight of said moisture barrier dry weight, wherein the amount of the said moisture barrier applied is no more than about 2.5% of the tablet dry weight,
- wherein said tablet contains at least about 95% undegraded bupropion hydrochloride after storage for 12 months at about 25° C.±2° C./60% RH±5% RH.
1 more element
A modified-release tablet comprising:
- (i) a core comprising an effective amount of bupropion hydrochloride and conventional excipients;
- (ii) a control-releasing coat surrounding said core, said control-releasing coat comprising a water-insoluble water-permeable film-forming polymer, a plasticizer and a water-soluble polymer, and
- (iii) a moisture barrier surrounding said control-releasing coat, said moisture barrier comprising, methacrylic acid copolymer, polyethylene glycol 1450, triethyl citrate and silicon dioxide, wherein said methacrylic acid copolymer is present at about 66% by weight of said moisture barrier dry weight, said polyethylene glycol 1450 and triethyl citrate is present at about 10% by weight of said moisture barrier dry weight in a proportion of about 1 part triethyl citrate to about 2 parts polyethylene glycol 1450 and said silicon dioxide is present at about 25% by weight of said moisture barrier dry weight, wherein the amount of the said moisture barrier applied is no more than about 2.5% of the tablet dry weight,
- wherein the moisture content is no more than about 1% in said tablet when stored at 40° C.±2° C./75% RH±5% RH after storage for about 6 months.
1 more element
A modified-release tablet comprising:
- (i) a core comprising an effective amount of bupropion hydrochloride and conventional excipients;
- (ii) a control-releasing coat surrounding said core, said control-releasing coat comprising a water-insoluble water-permeable film-forming polymer, a plasticizer and a water-soluble polymer, and
- (iii) a moisture barrier surrounding said control-releasing coat, said moisture barrier comprising, methacrylic acid copolymer, polyethylene glycol 1450, triethyl citrate and silicon dioxide, wherein said methacrylic acid copolymer is present at about 66% by weight of said moisture barrier dry weight, said polyethylene glycol 1450 and triethyl citrate is present at about 10% by weight of said moisture barrier dry weight in a proportion of about 1 part triethyl citrate to about 2 parts polyethylene glycol 1450 and said silicon dioxide is present at about 25% by weight of said moisture barrier dry weight, wherein the amount of the said moisture barrier applied is no more than about 2.5% of the tablet dry weight,
- wherein said tablet contains at least about 95% undegraded bupropion hydrochloride after storage for 18 months at about 25° C.±2° C./60% RH±5% RH.
1 more element
A modified-release tablet comprising:
- (i) a core comprising about 150 mg of bupropion hydrochloride, about 5.3 mg polyvinyl alcohol, about 4.7 mg glyceryl behenate;
- (ii) a control-releasing coat surrounding said core, said control-releasing coat comprising about 12 mg ethyl cellulose grade PR 100, about 3 mg polyethylene glycol 1450, and about 9 mg polyvinylpyrrolidone, wherein about 24 mg of the control releasing coat is applied onto said core;
- and
- (iii) a moisture barrier surrounding said control-releasing coat, said moisture barrier comprising about 4.6 mg methacrylic acid copolymer, about 0.46 mg polyethylene glycol 1450, about 0.23 mg triethyl citrate and about 1.72 mg silicon dioxide, wherein about 7 mg of the moisture barrier is applied onto the control releasing coated cores, and
- wherein said modified-release tablet is bioequivalent and exhibits a dissolution profile such that after about 2 hours about 5% of the bupropion hydrochloride content is released, after about 4 hours, about 32% of the bupropion hydrochloride content is released, after about 8 hours, about 74% of the bupropion hydrochloride content is released and after about 16 hours no less than about 99% of the bupropion hydrochloride content is released.
2 more elements
A modified-release tablet comprising:
- (i) a core comprising about 300 mg of bupropion hydrochloride, about 10.6 mg polyvinyl alcohol, about 9.4 mg glyceryl behenate;
- (ii) a control-releasing coat surrounding said core, said control-releasing coat comprising about 13.1 mg ethyl cellulose grade PR 100, about 3.6 mg polyethylene glycol 1450, and 12.4 mg polyvinylpyrrolidone, wherein about 29 mg of the control releasing coat is applied onto said core;
- and
- (iii) a moisture barrier surrounding said control-releasing coat, said moisture barrier comprising about 6.9 mg methacrylic acid copolymer, about 0.7 mg polyethylene glycol 1450, 0.35 mg triethyl citrate and about 2.6 mg silicon dioxide, wherein about 10.5 mg of the moisture barrier is applied onto the control releasing coated cores, and
- wherein said modified-release tablet is bioequivalent and exhibits a dissolution profile such that after about 2 hours about 5% of the bupropion hydrochloride content is released, after about 4 hours, about 32% of the bupropion hydrochloride content is released, after about 8 hours, about 74% of the bupropion hydrochloride content is released and after about 16 hours no less than about 99% of the bupropion hydrochloride content is released.
2 more elements
Dependencies are inferred from the claim text.