Modified release formulations containing drug-ion exchange resin complexes

• US 9,549,989 B2
• Filed: 02/18/2016
• Issued: 01/24/2017
• 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:
  US15/047,388
• Publication Number:
  US 20160158373A1
• Time in Patent Office: 341 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 particulate, barrier coated drug-anion exchange resin complex comprising a core composed of an acidic drug complexed with a pharmaceutically acceptable ion-exchange resin is provided. The barrier coating contains a polyvinyl acetate polymer and a plasticizer. Methods of making and products containing this coated complex are described.

Claims

1. A powder comprising a particulate drug-anion exchange resin complex comprising:

(a) a pharmaceutically acceptable acidic drug bound to a pharmaceutically acceptable, water insoluble, anion exchange resin to form the particulate drug-anion exchange resin complex, said complex optionally being in a matrix with a water insoluble polymer or copolymer or hydrophilic polymer, wherein said drug is a drug subject to abuse by humans, and

(b) a cured, high tensile strength, water permeable, water insoluble, non-ionic, polymeric diffusion barrier coating over the particulate drug-anion exchange resin complex-optional matrix defined in (a), wherein the cured barrier coating comprises;

(i) 70% w/w to 90% w/w polyvinylacetate polymer;

(ii) polyvinylpyrrolidone, and

(iii) an amount of plasticizer effective to enhance the tensile strength of said cured barrier coating,

wherein the powder may optionally be admixed with an aqueous suspension base for use as an oral suspension.

2. The powder according to claim 1, wherein the cured barrier coating has an elongation factor of 125% to 400%.

3. The powder according to claim 1, wherein the plasticizer is about 2% to about 20% by weight of the barrier coating.

4. The powder according to claim 3, wherein the plasticizer is about 5% to about 10% by weight of the barrier coating.

5. The powder according to claim 1, wherein the polyvinylpyrrolidone is about 5% by weight to about 10% by weight of the barrier coating.

6. The powder according to claim 1, wherein the polyvinylacetate is about 75% to about 85% by weight of the barrier coating.

7. The powder according to claim 1, wherein the anion exchange resin is a cholestyramine resin.

8. The powder according to claim 1, wherein the anion exchange resin is a copolymer comprising styrene and divinylbenzene comprising quaternary ammonium functional groups.

9. The powder according to claim 1, wherein the particulate drug-anion exchange resin complex is in a matrix with a water insoluble polymer or copolymer or a hydrophilic polymer, which polymer or copolymer is present in an amount of about 3% to about 30% by weight, based on the weight of the particulate drug-anion exchange resin complex-matrix and wherein the barrier coating is over the drug-anion exchange resin complex-matrix.

10. The powder according to claim 9, wherein the particulate drug-anion exchange resin complex-matrix comprises about 5% to about 20% by weight of said water insoluble polymer or copolymer or a hydrophilic polymer.

11. The powder according to claim 9, wherein the particulate drug-anion exchange resin complex-matrix of claim 9 is capable of passing through a number 40 mesh screen.

12. The powder according to claim 9, wherein the particulate matrix comprises the particulate drug-anion exchange resin complex and the hydrophilic polymer.

13. An aqueous oral suspension comprising water having suspended therein the powder according to claim 1.

14. The suspension according to claim 13, further comprising one or more active components which are not in the drug-anion exchange resin complex.