Modified release formulations containing drug—ion exchange resin complexes

• US 9,522,191 B2
• Filed: 10/07/2014
• Issued: 12/20/2016
• 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:
  US14/508,613
• Publication Number:
  US 20150024059A1
• Time in Patent Office: 805 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

An aqueous liquid suspension containing a coated drug-ion exchange resin complex comprising a core composed of an amphetamine complexed with a pharmaceutically acceptable ion-exchange resin and an uncoated amphetamine-ion exchange resin complex is provided. The coated amphetamine-ion exchange resin complex is in admixture with a polymer to form a matrix. Methods of making the coated complex and the liquid suspension are described.

Claims

1. An aqueous pharmaceutical liquid suspension suitable for oral ingestion comprising:

(i) a particulate drug-ion exchange resin complex-matrix comprising a pharmaceutically acceptable drug which is carbinoxamine bound to a pharmaceutically acceptable water insoluble ion exchange resin to form said particulate drug-ion exchange resin complex, said particulate drug-ion exchange resin complex being 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 said particulate drug-ion exchange resin complex-matrix, said ion exchange resin being a cation exchange resin, and

(ii) a cured, high tensile strength, water permeable, water insoluble, non-ionic polymeric diffusion modified release barrier coating over said particulate drug-ion exchange resin complex defined in (i), said cured, high tensile strength, water permeable, water insoluble, non-ionic polymeric, modified release, diffusion barrier coating applied as an aqueous dispersion, wherein said cured, high tensile strength, water permeable, water insoluble, non-ionic polymeric, modified release diffusion barrier coating comprises;

(a) about 75% w/w to about 90% w/w polyvinylacetate polymer;

(b) a stabilizer comprising polyvinylpyrrolidone, and

(c) about 2.5% w/w to about 20% w/w of plasticizer effective to enhance the tensile strength of said cured, high tensile strength, water permeable, water insoluble, non- ionic polymeric, modified release diffusion barrier coating, whereby said cured, high tensile strength, water permeable, water insoluble, non-ionic polymeric, modified release, diffusion barrier coating is over the particulate drug-ion exchange resin complex-matrix and provides a modified release profile to said pharmaceutically acceptable drug in said particulate drug- ion exchange resin complex-matrix.

2. The suspension according to claim 1, wherein said cured, high tensile strength, water permeable, water insoluble, non-ionic polymeric, modified release, diffusion barrier coating has an elongation factor of between about 125% and about 400%.

3. The suspension according to claim 1, wherein said particulate drug-ion exchange resin complex-matrix of (i) is capable of passing through a number 40 mesh screen.

4. The suspension according to claim 1, wherein said particulate drug-ion exchange resin complex-matrix of (i) comprises about 5% to about 20% by weight of said water insoluble polymer or copolymer or a hydrophilic polymer.

5. The suspension according to claim 1, wherein said particulate drug-ion exchange resin complex-matrix comprises said particulate drug-ion exchange resin complex and said hydrophilic polymer.

6. The suspension according to claim 5, wherein said hydrophilic polymer in said particulate drug-ion exchange resin complex-matrix comprises polyvinylpyrrolidone.

7. The suspension according to claim 1, wherein said particulate drug-ion exchange resin complex-matrix comprises said particulate drug-ion exchange resin complex and said water insoluble polymer or copolymer.

8. The suspension according to claim 7, wherein said water insoluble polymer in said particulate drug-ion exchange resin complex-matrix comprises polyvinylacetate, wherein said particulate matrix comprises said particulate drug-ion exchange resin complex, a stabilizer comprising polyvinylpyrrolidone and an effective amount of a surfactant.

9. The suspension according to claim 1, further comprising an orally ingestible drug bound to a pharmaceutically acceptable, water insoluble ion exchange resin to form an uncoated particulate drug-ion exchange resin complex, wherein said drug in said uncoated complex is either the same as or different from the pharmaceutically acceptable drug in (i).

10. The suspension according to claim 1, wherein said plasticizer comprises about 5% to about 10% w/w of said cured modified release barrier coating.

11. The suspension according to claim 10, wherein said plasticizer comprises triacetin.

12. The suspension according to claim 1, wherein said cured, high tensile strength, water permeable, water insoluble, non-ionic polymeric, modified release diffusion barrier coating further comprises a surfactant.

13. The suspension according to claim 1, wherein said cured, high tensile strength, water permeable, water insoluble, non-ionic polymeric, modified release diffusion barrier coating comprises about 25% to about 50% by weight of the particulate drug-ion exchange resin complex-matrix defined in (i).

14. The suspension according to claim 13, wherein said cured, high tensile strength, water permeable, water insoluble, non-ionic polymeric, modified release diffusion barrier coating comprises about 30% to about 45% by weight of the particulate barrier coated drug-ion exchange resin complex-matrix defined in (i).

15. An aqueous pharmaceutical liquid suspension suitable for oral ingestion comprising:

(i) a particulate carbinoxamine-cation exchange resin complex comprising carbinoxamine bound to a pharmaceutically acceptable water insoluble cation exchange resin to form said particulate carbinoxamine-cation exchange resin complex, said particulate carbinoxamine-cation exchange resin complex optionally being in a matrix with a water insoluble polymer or copolymer or a hydrophilic polymer, and

(ii) a cured, high tensile strength, water permeable, water insoluble, non-ionic polymeric, modified release diffusion barrier coating over said particulate carbinoxamine-cation exchange resin complex-optional matrix defined in (i), said cured, high tensile strength, water permeable, water insoluble, non-ionic polymeric, modified release diffusion barrier coating applied as an aqueous dispersion, wherein said cured, high tensile strength, water permeable, water insoluble, non-ionic polymeric, modified release diffusion barrier coating comprises;

(a) about 75% w/w to about 90% w/w polyvinylacetate polymer; and

(b) a stabilizer comprising polyvinylpyrrolidone, and

(c) about 2.5% w/w to about 20% w/w of plasticizer effective to enhance the tensile strength of said cured, high tensile strength, water permeable, water insoluble, non-ionic polymeric, modified release diffusion barrier coating, whereby said cured, high tensile strength, water permeable, water insoluble, non-ionic polymeric, modified release diffusion barrier coating is over the particulate carbinoxamine-cation exchange resin complex-optional matrix and provides a modified release profile to said pharmaceutically acceptable drug in said particulate carbinoxamine-cation exchange resin complex-optional matrix.

16. The suspension according to claim 15, wherein the matrix is present and comprises the particulate carbinoxamine-cation exchange resin complex and about 3% to about 30% by weight of the hydrophilic polymer, based on the weight of the particulate carbinoxamine-cation exchange resin complex-matrix.

17. The suspension according to claim 15, wherein the matrix is present and comprises the particulate carbinoxamine-cation exchange resin complex and about 5% to about 20% by weight of the hydrophilic polymer, based on the weight of the particulate carbinoxamine-cation exchange resin complex-matrix.

18. An aqueous pharmaceutical liquid suspension suitable for oral ingestion comprising:

(i) a particulate carbinoxamine-cation exchange resin complex-matrix comprising carbinoxamine bound to a pharmaceutically acceptable water insoluble cation exchange resin to form said particulate carbinoxamine-cation exchange resin complex-matrix, wherein the matrix comprises the particulate carbinoxamine-cation exchange resin complex and a polymer or copolymer in an amount of about 3% to about 30% of the particulate carbinoxamine-cation exchange resin complex-matrix; and

(ii) about 25% w/w to about 50% w/w cured, high tensile strength, water permeable, water insoluble, non-ionic polymeric, modified release diffusion barrier coating over said particulate carbinoxamine-cation exchange resin complex defined in (i), said cured, high tensile strength, water permeable, water insoluble, non-ionic polymeric, modified release diffusion barrier coating over the particulate carbinoxamine-cation exchange resin complex-matrix and provides a modified release profile to said pharmaceutically acceptable drug in said particulate carbinoxamine-cation exchange resin complex-matrix.

19. The suspension according to claim 18, wherein the modified release barrier coating is present in an amount of about 30% w/w to about 45% w/w of the barrier coated particulate carbinoxamine-cation exchange resin complex.