Sustained-release formulations of topiramate
AssigneeSupernus Pharmaceuticals, Inc.
InventorsLikan Liang, Hua Wang, Padmanabh P. Bhatt, Michael L. Vieira
Life of this patent
Estimating the term…
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.
Claims31
A sustained release formulation of topiramate comprising topiramate as an active ingredient, which is released from the formulation along a pre-determined release profile, the formulation comprising:
- (a) at least two different extended release topiramate-containing components, wherein each component comprises a release controlling coating specific for its component and comprising a coating material selected from the group consisting of cellulosic polymers and acrylic polymers, and, optionally,
- (b) an immediate release (IR) topiramate-containing component comprising:
- (i) a complexing agent selected from the group consisting of hydroxypropyl-beta-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin, alpha-cyclodextrin, cyclodextrin, and cyclodextrin derivative, and/or
- (ii) 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;
- wherein all of the components release topiramate in a continuous manner and at least one of the two XR components releases the topiramate contained therein such that greater than or equal to about 80% of the topiramate is released in vitro in less than or equal to about 4 hours.
A sustained release formulation of topiramate comprising topiramate as an active ingredient, which is released from the formulation along a pre-determined release profile, the formulation comprising:
- (a) at least two different extended release topiramate-containing components, wherein each component comprises a release controlling coating specific for its component and comprising a coating material selected from the group consisting of cellulosic polymers and acrylic polymers, and, optionally,
- (b) an immediate release (IR) topiramate-containing component comprising:
- (i) a complexing agent selected from the group consisting of hydroxypropyl-beta-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin, alpha-cyclodextrin, cyclodextrin, and cyclodextrin derivative, and/or
- (ii) 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;
- wherein all of the components release topiramate in a continuous manner and at least one of the two XR components releases the topiramate contained therein such that greater than or equal to about 80% of the topiramate is released in vitro in less than or equal to about 4 hours, and wherein the components in the formulation are present according to the following proportions:
- F. No.
- 1
- 2
- 3
- 4
- 5
- % XR1
- 20
- 50
- 10
- 10
- 15
- % XR2
- 80
- 0
- 84
- 80
- 70
- % XR3
- 0
- 50
- 0
- 0
- 15
- % IR
- 0
- 0
- 6
- 10
- 0
- wherein XR1, XR2, XR3, and IR release topirmate in a continuous manner such that:
- 1. for in-vitro dissolution,
- for XR1, 1.5 h<=T80%<=4 h;
- for XR2, 5 h<=T80%<=8 h;
- for XR3, 8 h<T80%<=10 h;
- for IR, T80%<=1 h;
- and/or
- 2. for a single initial dose in vivo,
- for XR1, 4 h<=Tmax<=8.5 h;
- for XR2, Tmax>=16 h;
- for XR3, Tmax>=16 h.
Dependencies are inferred from the claim text.