Modified release formulations containing drug-ion exchange resin complexes

• US 9,198,864 B2
• Filed: 06/10/2015
• Issued: 12/01/2015
• Est. Priority Date: 03/16/2006
• Status: Active Grant

• Current Assignee: Tris Pharma Incorporated
• Original Assignee: Tris Pharma Incorporated
• Inventors: Mehta, Ketan, Tu, Yu-Hsing
• Primary Examiner(s): Tran, Susan
• Assistant Examiner(s): CRAIGO, WILLIAM A
• Application Number:
  US14/735,526
• Publication Number:
  US 20150272893A1
• Time in Patent Office: 174 Days
• Field of Search: None
• US Class Current: 1/1
• 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 tablet comprising a coated drug-ion exchange resin complex composed of methylphenidate complexed with a pharmaceutically acceptable ion-exchange resin and an uncoated methylphenidate-ion exchange resin complex is provided. The coated methylphenidate-ion exchange resin complex is in admixture with a polymer to form a matrix. Also provided is a tablet comprising a coated drug-ion exchange resin complex composed of dexmethylphenidate complexed with a pharmaceutically acceptable ion-exchange resin and an uncoated dexmethylphenidate-ion exchange resin complex is provided. The coated dexmethylphenidate-ion exchange resin complex is in admixture with a polymer to form a matrix.

Claims

1. A solid pharmaceutical orally disintegrating tablet comprising:

(a) drug-ion exchange resin complex particles that are uncoated and which comprise methylphenidate bound to an ion exchange resin, and

(b) modified release coated drug-ion exchange resin complex particles which comprise methylphenidate bound to an ion exchange resin, wherein said modified release coated drug-ion exchange resin complex particles (b) further comprise a hydrophilic polymer or water insoluble polymer or copolymer in a matrix with the drug-ion exchange resin complex, wherein the modified release coating is over the drug-ion exchange resin complex-matrix

wherein the weight ratio of (a) to (b) is about 2;

1 to about 1;

10.

2. The tablet according to claim 1, wherein the modified release coating on the coated drug-ion exchange resin complex particles is a delayed release coating.

3. The tablet according to claim 1, wherein said modified release coated drug-ion exchange resin complex particles (b) further comprise a water insoluble polymer or copolymer in a matrix with the drug-ion exchange resin complex, wherein the modified release coating is over the drug-ion exchange resin complex-matrix.

4. The tablet according to claim 3, wherein the water insoluble polymer or copolymer is selected from the group consisting of a polyvinyl acetate polymer, cellulose acetate, acrylic based polymers or copolymers, cellulose phthalate, and mixtures thereof.

5. The tablet according to claim 1, wherein the ion exchange resin in (a) and/or (b) is a strong acidic cation exchange resin.

6. The tablet according to claim 5, wherein said strong acidic cation exchange resin is a sulfonated copolymer of a polystyrene crosslinked with divinylbenzyl.

7. The tablet according to claim 1, wherein the drug-ion exchange resin complex particles of (a) and/or (b) have a particle size in the range of about 40 to about 250 microns.

8. A solid pharmaceutical orally disintegrating tablet comprising:

(a) drug-ion exchange resin complex particles that are uncoated and which comprise dexmethylphenidate bound to an ion exchange resin, and

(b) modified release coated drug-ion exchange resin complex particles which comprise dexmethylphenidate bound to an ion exchange resin, wherein said modified release coated drug-ion exchange resin complex particles (b) further comprise a hydrophilic polymer or water insoluble polymer or copolymer in a matrix with the drug-ion exchange resin complex, wherein the modified release coating is over the drug-ion exchange resin complex-matrix

wherein the weight ratio of (a) to (b) is about 2;

1 to about 1;

10.

9. The tablet according to claim 8, wherein the modified release coating on the coated drug-ion exchange resin complex particles is a delayed release coating.

10. The tablet according to claim 8, wherein said modified release coated drug-ion exchange resin complex particles (b) further comprise a water insoluble polymer or copolymer in a matrix with the drug-ion exchange resin complex, wherein the modified release coating is over the drug-ion exchange resin complex-matrix.

11. The tablet according to claim 10, wherein the water insoluble polymer or copolymer is selected from the group consisting of a polyvinyl acetate polymer, cellulose acetate, acrylic based polymers or copolymers, cellulose phthalate, and mixtures thereof.

12. The tablet according to claim 8, wherein the ion exchange resin in (a) and/or (b) is a strong acidic cation exchange resin.

13. The tablet according to claim 12, wherein said strong acidic cation exchange resin is a sulfonated copolymer of a polystyrene crosslinked with divinylbenzyl.

14. The tablet according to claim 8, wherein the drug-ion exchange resin complex particles of (a) and/or (b) have a particle size in the range of about 40 to about 250 microns.