.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Claims for Patent: 8,298,576

« Back to Dashboard

Claims for Patent: 8,298,576

Title:Sustained-release formulations of topiramate
Abstract: Pharmaceutical compositions of topiramate for once-a-day oral administration are provided. The formulations comprise a sustained-release component and an optional immediate-release component, the compositions of which can be selectively adjusted, respectively, to release the active ingredient along a pre-determined release profile. Method of treating or preventing pathological disorders in mammalian subjects comprising the administration of the novel formulations disclosed herein is also provided.
Inventor(s): Liang; Likan (Boyds, MD), Wang; Hua (Clarksville, MD), Bhatt; Padmanabh P. (Rockville, MD), Vieira; Michael L. (Gaithersburg, MD)
Assignee: Supernus Pharmaceuticals, Inc. (Rockville, MD)
Application Number:11/941,475
Patent Claims: 1. A sustained release formulation of topiramate for oral administration to a mammalian subject comprising an immediate release bead population (IR), a first extended release bead population (XR1), and a second extended release bead population (XR2), wherein: (a) the IR bead population comprises topiramate up to 10% by wt of the total amount of topiramate in the formulation and 0.1-10% by wt of a binder, wherein the topiramate and binder form a coating on inert carrier particles, wherein the coated inert carrier particles are not coated with a release controlling coating, and wherein the IR bead population releases greater than or equal to 80% of its topiramate in a continuous manner over less than or equal to 1 hour; (b) the XR1 bead population comprises topiramate up to 20% by wt of the total amount of topiramate in the formulation, wherein the topiramate is a coating on inert carrier particles, wherein the topiramate coated inert carrier particles are further coated with a release controlling coating material, wherein the coating material comprises 2-15% by weight of the topiramate coated inert carrier particles, and wherein the XR1 bead population releases 80% of its topiramate in a continuous manner over less than or equal to 4 hours; and, (c) the XR2 bead population comprises topiramate at least 80% by weight of the total amount of topiramate in the formulation, wherein the topiramate is a coating on inert carrier particles, wherein the topiramate coated inert carrier particles are coated with a release controlling coating material, wherein the coating material comprises 2-15% by weight of the topiramate coated inert carrier particles, and wherein the XR2 bead population releases 80% of its topiramate in a continuous manner over less than 8 hours; wherein the release controlling coating materials comprise methylcellulose, ethylcellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, cellulose acetate, cellulose acetate phthalate, polyvinyl alcohol, polyacrylates, polymethacrylates or copolymers thereof, and wherein the XR1 and XR2 bead populations have their own specific rates of release.

2. The sustained release foimulation according to claim 1, wherein the binder is selected from the group consisting of starches, microcrystalline cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, and polyvinylpyrrolidone.

3. The sustained release formulation according to claim 1, wherein the IR bead population further comprises an enhancing agent selected from the group consisting of Vitamin E TPGS, glutamic acid, glycine, sorbitol, mannose, amylose, maltose, mannitol, lactose, sucrose, glucose, xylitose, dextrins, glycerol-polyethylene glycol oxystearate, polyethylene glycol-32 glyceryl palmitostearate, sodium lauryl sulfate, polyoxyethylene sorbitan monooleate, benzyl alcohol, sorbitan monolaurate, polyethylene-polypropylene glycol, polyethylene glycol-3350, polyvinylpyrrolidone-K25, oleic acid, glyceryl monooleate, sodium benzoate, cetyl alcohol, sucrose stearate, crospovidone, sodium starch glycolate, croscarmellose sodium, carboxymethylcellulose, starch, pregelatinized starch, hydroxypropylmethylcellulose HPMC, substituted hydroxypropylcellulose, microcrystalline cellulose sodium bicarbonate, calcium citrate, sodium docusate, menthol, and combinations thereof.

4. The sustained release formulation according to claim 1, wherein the IR bead population further comprises a complexing agent selected from the group consisting of cyclodextrin, hydroxypropyl-beta-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin, alpha-cyclodextrin, and derivatives thereof.

5. The sustained release formulation according to claim 1, wherein the XR1 and/or XR2 bead populations further comprises a pore former selected from the group consisting of glucose, fructose, mannitol, mannose, galactose, sorbitol, pullulan, dextran, hydroxyalkylcelluloses, carboxyalkylcelluloses, hydroxypropylmethylcellulose, cellulose ethers, acrylic resins, polyvinylpyrrolidone, cross-linked polyvinylpyrrolidone, polyethylene oxide, carbomer, diols, polyols, polyhydric alcohols, polyalkylene glycols, polyethylene glycols, polypropylene glycols or block polymers thereof, polyglycols, poly(.alpha.-.omega.)alkylenediols; alkali metal salts and alkaline earth metal salts, and combinations thereof.

6. The formulation of claim 1, wherein the IR bead population releases greater than or equal to 80% of its topiramate in less than or equal to 30 minutes.

7. The formulation of claim 1, wherein at least a part of the active ingredient is in a form of micronized particles.

8. The formulation of claim 1, wherein said formulation is in a dosage form of a tablet, a pill, a capsule, a caplet, a troche, a pouch, or sprinkles.

9. The formulation of claim 1, wherein the total amount of topiramate in the formulation is from 0.5 to 3000 mg.

10. The formulation of claim 1, wherein the inert carrier particles comprise cellulose spheres, silicon dioxide, starch or sugar spheres.

11. The sustained release formulation according to claim 1, wherein the coating material comprises methylcellulose, ethylcellulose, hydroxypropyl cellulose, or hydroxypropylmethyl cellulose.

12. The formulation of claim 1, wherein said formulation provides for a maximum steady state plasma concentration (Cmax) of topiramate which is in the range from 50% to 125% of the maximum plasma concentration produced by the same amount of topiramate administered as an immediate release formulation BID.

13. The formulation of claim 1, wherein said formulation provides for a relative steady state AUC in the range of 80% to 125% of the AUC of the same amount of topiramate administered as an immediate release formulation BID.

14. The formulation of claim 1, further comprising an additional pharmaceutically active ingredient in combination with topiramate.

15. A method of treatment of a neurological and/or psychiatric condition in a mammalian subject, comprising orally administering to the subject a therapeutically effective amount of the sustained release formulation of claim 1.

16. The method of claim 15, wherein said condition is selected from a group consisting of epilepsy, migraine, essential tremor, restless limb syndrome, cluster headaches, neuralgia, neuropathic pain, Tourrette's syndrome, infantile spasms, bipolar disorder, dementia, depression, psychosis, mania, anxiety, schizophrenia, obsessive-compulsive disorder, post-traumatic stress disorder, attention deficit hyperactivity disorder, impulse control disorders, border line personality disorder, addiction, autism, chronic neurodegenerative disorders, acute neurodegeneration, amyotrophic lateral sclerosis.

17. The method of claim 15, wherein the condition is epilepsy.

18. The method of claim 15, wherein the condition is migraine.

19. A sustained release formulation of topiramate comprising: (a) a first extended release bead population (XR1) comprising up to 20% by wt of the total amount of topiramate in the formulation, wherein the topiramate is a coating on inert carrier particles and further coated with a release controlling coating material, wherein the release controlling material releases 80% of the topiramate in a continuous manner over less than or equal to 4 hours; and, (b) a second extended release bead population (XR2) comprising at least 80% by weight of the total amount of topiramate in the formulation, wherein the topiramate is coated onto inert carrier particles and further coated with a release controlling coating material, wherein the release controlling material releases 80% of the topiramate in a continuous manner over less than 8 hours; wherein the release controlling coating materials comprise methylcellulose, ethylcellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, cellulose acetate, cellulose acetate phthalate, polyvinyl alcohol, polyacrylates, polymethacrylates or copolymers thereof; and wherein the XR1 and XR2 bead populations have their own specific rates of release.

20. The sustained release formulation according to claim 19, further comprising: (c) an immediate release (IR) bead population comprises topiramate up to 10% by wt of the total amount of topiramate in the formulation and 0.1-10% by wt of a binder, wherein the topiramate and binder form a coating on inert carrier particles, and wherein the IR bead population releases greater than or equal to 80% of its topiramate in a continuous manner over less than or equal to 1 hour.

21. The sustained release formulation according to claim 20, wherein the IR bead population further comprises an enhancing agent selected from the group consisting of Vitamin E TPGS, glutamic acid, glycine, sorbitol, mannose, amylose, maltose, mannitol, lactose, sucrose, glucose, xylitose, dextrins, glycerol-polyethylene glycol oxystearate, polyethylene glycol-32 glyceryl palmitostearate, sodium lauryl sulfate, polyoxyethylene sorbitan monooleate, benzyl alcohol, sorbitan monolaurate, polyethylene-polypropylene glycol, polyethylene glycol-3350, polyvinylpyrrolidone-K25, oleic acid, glyceryl monooleate, sodium benzoate, cetyl alcohol, sucrose stearate, crospovidone, sodium starch glycolate, croscarmellose sodium, carboxymethylcellulose, starch, pregelatinized starch, hydroxypropylmethylcellulose, substituted hydroxypropylcellulose, microcrystalline cellulose sodium bicarbonate, calcium citrate, sodium docusate, menthol, and combinations thereof.

22. The sustained release formulation according to claim 19, further comprising: (c) a third extended release bead population (XR3) comprising up to 15% by weight of the total amount of topiramate in the formulation, wherein the topiramate is coated onto inert carrier particles and further coated with a release controlling coating material, wherein the release controlling material releases 80% of the topiramate in a continuous manner over less than or equal to 10 hours.

23. The sustained release formulation according to claim 19, wherein the XR1 and/or XR2 bead populations further comprises a pore former selected from the group consisting of glucose, fructose, mannitol, mannose, galactose, sorbitol, pullulan, dextran, hydroxyalkylcelluloses, carboxyalkylcelluloses, hydroxypropylmethylcellulose, cellulose ethers, acrylic resins, polyvinylpyrrolidone, cross-linked polyvinylpyrrolidone, polyethylene oxide, carbomer, diols, polyols, polyhydric alcohols, polyalkylene glycols, polyethylene glycols, polypropylene glycols or block polymers thereof, polyglycols, poly(.alpha.-.omega.)alkylenediols; alkali metal salts and alkaline earth metal salts, and combinations thereof.

24. The sustained release formulation according to claim 19, wherein the coating material comprises methylcellulose, ethylcellulose, hydroxypropyl cellulose, or hydroxypropylmethyl cellulose.

25. The formulation of claim 19, wherein said formulation provides for a relative steady state AUC in the range of 80% to 125% of the AUC of the same amount of topiramate administered as an immediate release formulation BID.

26. The formulation of claim 19, further comprising an additional pharmaceutically active ingredient in combination with topiramate.

27. A method of treatment of a neurological and/or psychiatric condition in a mammalian subject, comprising orally administering to the subject a therapeutically effective amount of the sustained release formulation of claim 19.

28. The method of claim 27, wherein said condition is selected from a group consisting of epilepsy, migraine, essential tremor, restless limb syndrome, cluster headaches, neuralgia, neuropathic pain, Tourrette's syndrome, infantile spasms, bipolar disorder, dementia, depression, psychosis, mania, anxiety, schizophrenia, obsessive-compulsive disorder, post-traumatic stress disorder, attention deficit hyperactivity disorder, impulse control disorders, border line personality disorder, addiction, autism, chronic neurodegenerative disorders, acute neurodegeneration, amyotrophic lateral sclerosis.

29. The method of claim 28, wherein the condition is epilepsy.

30. The method of claim 28, wherein the condition is migraine.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc