Modified release formulations containing drug-ion exchange resin complexes

• US 9,675,704 B2
• Filed: 07/01/2016
• Issued: 06/13/2017
• Est. Priority Date: 03/16/2006
• Status: Active Grant

• Current Assignee: Tris Pharma Incorporated
• Original Assignee: Tris Pharma Incorporated
• Inventors: Tu, Yu-Hsing, Mehta, Ketan
• Primary Examiner(s): Tran, Susan
• Assistant Examiner(s): CRAIGO, WILLIAM A
• Application Number:
  US15/200,786
• Publication Number:
  US 20160310449A1
• Time in Patent Office: 347 Days
• Field of Search: None
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 31/24 having an amino or nitro group
• CPC Class Codes: A61K 31/4402 only substituted in position 2, e.g. pheniramine, bisacodyl
• CPC Class Codes: A61K 31/4458 only substituted in position 2, e.g. methylphenidate
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/585 Ion exchange resins, e.g. polystyrene sulfonic acid resin
• CPC Class Codes: A61K 47/6921 the form being a particulate, a powder, an adsorbate, a bead or a sphere
• CPC Class Codes: A61K 47/6927 the form being a solid microparticle having no hollow or gas-filled cores
• CPC Class Codes: A61K 47/6933 the polymer being obtained by reactions only involving carbon to carbon, e.g. poly(meth)acrylate, polystyrene, polyvinylpyrrolidone or polyvinylalcohol
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61K 9/14 : Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61K 9/1635 : obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1664 : Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/1617
• CPC Class Codes: A61K 9/167 : with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface with further drug-free outer coating A61K9/5073
• CPC Class Codes: A61K 9/2013 : Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2027 : obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2031 : obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/2077 : Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61K 9/2081 : with microcapsules or coated microparticles according to A61K9/50
• CPC Class Codes: A61K 9/4866 : Organic macromolecular compounds
• CPC Class Codes: A61K 9/5021 : Organic macromolecular compounds
• CPC Class Codes: A61K 9/5026 : obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61P 25/04 : Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/26 : Psychostimulants, e.g. nicotine, cocaine

Abstract

A particulate, pH-independent, modified release barrier coated drug-cation exchange resin complex comprising a core composed of a drug complexed with a pharmaceutically acceptable ion-exchange resin is provided. Methods of making and products containing this coated complex are described.

Claims

1. An orally ingestible solid dose composition comprising:

(A) barrier coated particulates which provide a modified release profile which comprises;

(i) a particulate drug-cation exchange resin complex comprising at least one drug bound to a pharmaceutically acceptable water insoluble cation exchange resin, said complex being in a matrix which further comprises a water insoluble polymer or copolymer, or hydrophilic polymer, wherein the particulate drug-cation exchange resin complex-matrix is capable of passing through a number 40 mesh screen, and

(ii) about 20 wt % to about 50 wt %, based on the weight of the drug-cation exchange resin complex, of a high tensile strength, water permeable, water insoluble, non ionic, modified release polymeric diffusion barrier coating which provides a modified release profile to said at least one drug in the drug-cation exchange resin complex-matrix defined in (i), said barrier coating having an elongation factor of about 125% to about 400%, wherein said at least one drug is amphetamine or dextro-amphetamine; and

(B) at least one of (iiia) and/or (iiib);

(iiia) an uncoated particulate dextro-amphetamine-cation exchange resin complex of a size capable of passing through a number 40 mesh screen, wherein said uncoated dextro-amphetamine-cation exchange resin complex is dextro-amphetamine bound to a pharmaceutically acceptable water insoluble cation exchange resin,

(iiib) an uncoated particulate amphetamine-cation exchange resin complex of a size capable of passing through a number 40 mesh screen, wherein said uncoated amphetamine-cation exchange resin complex is amphetamine bound to a pharmaceutically acceptable water insoluble cation exchange resin,

and optionally at least one of (iiic) and/or (iiid);

(iiic) amphetamine or a pharmaceutically acceptable salt thereof which is not complexed with an ion exchange resin, and/or

(iiid) dextroamphetamine or a pharmaceutically acceptable salt thereof which is not complexed with an ion exchange resin.

2. The orally ingestible solid dose composition according to claim 1, wherein the matrix comprises the water insoluble polymer or copolymer.

3. The orally ingestible solid dose composition according to claim 1, wherein the matrix comprises the hydrophilic polymer, wherein said hydrophilic polymer comprises polyvinylpyrrolidone.

4. The orally ingestible solid dose composition according to claim 1, wherein said high tensile strength, water permeable, water insoluble, non ionic polymeric diffusion barrier coating comprises about 30 wt % to about 45 wt % of the drug-cation exchange resin complex.

5. The orally ingestible solid dose composition according to claim 1 which comprises at least one of said uncoated particulate dextro-amphetamine-cation exchange resin as defined in (B)(iiia) and/or said uncoated particulate amphetamine-cation exchange resin as defined in (B)(iiib).

6. The orally ingestible solid dose composition according to claim 5 which comprises at least one of said amphetamine or pharmaceutically acceptable salt thereof as defined in (B)(iiic) or dextro-amphetamine or pharmaceutically acceptable salt as defined in (B)(iiid) which is not complexed with an ion exchange resin.

7. The orally ingestible solid dose composition according to claim 1 wherein said high tensile strength, water permeable, water insoluble non-ionic polymeric diffusion barrier coating further comprises a plasticizer in an amount of about 2% w/w to about 20 w/w % of the coating layer.

8. The orally ingestible solid dose composition according to claim 7, wherein said plasticizer comprises about 5% w/w to about 20% w/w of the coating.

9. The orally ingestible solid dose composition according to claim 1, wherein said cation exchange resin used to form the complex as defined in (A), (B)(iiia), and/or (B)(iiib) is a sulfonated copolymer comprising styrene and a divinylbenzene.

10. The orally ingestible solid dose composition according to claim 1, wherein said composition is a tablet.

11. An orally ingestible solid dose composition comprising:

(A) barrier coated particulates which provide about a twelve-hour release profile which comprises;

(i) a particulate drug-cation exchange resin complex comprising at least one drug bound to a pharmaceutically acceptable water insoluble cation exchange resin, said complex being in a matrix which further comprises a water insoluble polymer or copolymer, or hydrophilic polymer, wherein the particulate drug-cation exchange resin complex-matrix is capable of passing through a number 40 mesh screen, and

(ii) about 30 wt % to about 50 wt %, based on the weight of the drug-cation exchange resin complex, of a high tensile strength, water permeable, water insoluble, non ionic, modified release polymeric diffusion barrier coating which provides a modified release profile to said at least one drug in said drug-cation exchange resin complex-matrix, said barrier coating having an elongation factor of about 125% to about 400%, wherein said at least one drug is amphetamine or dextro-amphetamine; and

(B) at least one of (iiia) and/or (iiib);

(iiia) an uncoated particulate dextro-amphetamine-cation exchange resin complex of a size capable of passing through a number 40 mesh screen, wherein said uncoated dextro-amphetamine-cation exchange resin complex is dextro-amphetamine bound to a pharmaceutically acceptable water insoluble cation exchange resin,

(iiib) an uncoated particulate amphetamine-cation exchange resin complex of a size capable of passing through a number 40 mesh screen, wherein said uncoated amphetamine-cation exchange resin complex is amphetamine bound to a pharmaceutically acceptable water insoluble cation exchange resin,

and optionally at least one of (iiic) and/or (iiid);

(iiic) amphetamine or a pharmaceutically acceptable salt thereof which is not complexed with an ion exchange resin, and/or

(iiid) dextroamphetamine or a pharmaceutically acceptable salt thereof which is not complexed with an ion exchange resin.

12. The orally ingestible solid dose composition according to claim 11, wherein the matrix comprises the water insoluble polymer or copolymer to form the drug-cation exchange resin complex-matrix as defined in (A).

13. The orally ingestible solid dose composition according to claim 11, wherein the matrix comprises the hydrophilic polymer to form the drug-cation exchange resin complex as defined in (A), wherein the hydrophilic polymer comprises polyvinylpyrrolidone.

14. The orally ingestible solid dose composition according to claim 11, wherein said high tensile strength, water permeable, water insoluble, non ionic polymeric diffusion barrier coating comprises about 35 wt % to about 50 wt % of the drug-cation exchange resin complex.

15. The orally ingestible solid dose composition according to claim 11 which comprises at least one of said uncoated particulate dextro-amphetamine-cation exchange resin as defined in (B)(iiia) and/or said uncoated particulate amphetamine-cation exchange resin as defined in (B)(iiib).

16. The orally ingestible solid dose composition according to claim 15 which comprises at least one of said amphetamine or pharmaceutically acceptable salt thereof as defined in (B)(iiic) or dextro-amphetamine or pharmaceutically acceptable salt as defined in (B)(iiid) which is not complexed with an ion exchange resin.

17. The orally ingestible solid dose composition according to claim 11 wherein said high tensile strength, water permeable, water insoluble non-ionic polymeric diffusion barrier coating further comprises a plasticizer in an amount of about 2% w/w to about 20% of the coating layer.

18. The orally ingestible solid dose composition according to claim 17, wherein said plasticizer comprises about 5% w/w to about 20% w/w of the coating.

19. The orally ingestible solid dose composition according to claim 11, wherein said cation exchange resin used to form the complex as defined in (A), (B)(iiia), and/or (B)(iiib) is a sulfonated copolymer comprising styrene and a divinylbenzene.

20. The orally ingestible solid dose composition according to claim 11, wherein said composition is a tablet.