WO2014167439A1 - Modified release pharmaceutical compositions of topiramate or salts thereof - Google Patents
Modified release pharmaceutical compositions of topiramate or salts thereof Download PDFInfo
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- WO2014167439A1 WO2014167439A1 PCT/IB2014/060054 IB2014060054W WO2014167439A1 WO 2014167439 A1 WO2014167439 A1 WO 2014167439A1 IB 2014060054 W IB2014060054 W IB 2014060054W WO 2014167439 A1 WO2014167439 A1 WO 2014167439A1
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- topiramate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
Abstract
The present invention relates to modified release pharmaceutical compositions of topiramate or salts thereof. In particular, the present invention relates to modified release pharmaceutical compositions comprising at least two types of components, wherein at least one type of the component comprises a matrix of topiramate or salts thereof and one or more release modifying substances. The composition may provide extended and specific release of topiramate or salts thereof to achieve therapeutically effective plasma concentration over a period of 24 hours to treat epileptic conditions when administered to a patient in need thereof. The invention also includes process of preparing such composition.
Description
MODIFIED RELEASE PHARMACEUTICAL COMPOSITIONS OF
TOPIRAMATE OR SALTS THEREOF
Field of the Invention
The present invention relates to modified release pharmaceutical compositions of topiramate or salts thereof. By using at least two types of components, in which at least one type of the component comprising a matrix of topiramate or salts thereof and one or more release modifying substances, a modified release pharmaceutical composition of topiramate can be formed. The composition may provide extended and specific release of topiramate or salts thereof to achieve therapeutically effective plasma concentration over a period of 24 hours to treat epileptic conditions when administered to a patient in need thereof. The invention also includes process of preparing such composition.
Background of the Invention
Topiramate is a sulfamate-substituted monosaccharide approved in the US for use as an antiepileptic agent, as an adjuvant therapy for patients with partial onset seizures or primary generalized tonic-clonic seizures and marketed under the trade name of Topamax®. Topiramate has been also approved for the prophylaxis treatment of migraine headache. Chemically, topiramate is 2,3:4,5 Di-O-isopropylidene-p-D-fructopyranose sulfamate and has the following structural formula:
Many active pharmaceutical agents have been formulated as orally administrable extended release dosage form to permit once daily administration. Though topiramate has a relatively long half-life of 21 hours in vivo, it has not been
formulated as a single, daily-dose because of its side-effects that often result with peak plasma levels of the drug when taken in high doses.
Each administration of currently available Topamax®, an IR dosage form, is associated with a peak in plasma concentrations of the drug, and the fluctuations associated with the peaks and valleys of blood plasma levels of the drug causing undesirable effects. Moreover, it is associated with severe side-effects including somnolence, dizziness, ataxia, speech disorders and related speech problems, psychomotor slowing, abnormal vision, difficulty with memory, paresthesia, diplopia, renal calculi (kidney stones), hepatic failure, pancreatitis, renal tubular acidosis, acute myopia and secondary angle closure glaucoma. Moreover, administration of the medicament in this manner (immediate release form) is cumbersome and patients can forget to take their medication in a timely manner.
The extended release of drug can be achieved either by coating the composition with release modifying substance or by dispersing drug in a matrix comprising one or more release modifying substance. In case of matrix-type dosage form, the drug is released over a period of time in the gastrointestinal tract upon dissolution or erosion of the matrix.
Extended-release dosage forms comprising a matrix system are conveniently prepared as compressed tablets. But drugs having relatively high solubility in water, for example a solubility of about 5 mg/ml or greater, present challenges to the formulator wishing to provide an extended-release dosage form and the higher the solubility the greater are the challenges.
US Patent No. 7,125,560 discloses a pharmaceutical composition in the form of core particles containing topiramate with sugar spheres as diluent wherein the core particles are coated with a taste mask coating.
US Patent Nos. 7,61 1 ,728 and 7,351 ,695 discloses osmotic release pharmaceutical composition of topiramate and acceptable salts thereof.
US Patent No. 6,923,988 teaches the pharmaceutical compositions which can be used for improved delivery of hydrophilic or hydrophobic pharmaceutical active ingredients by encapsulating the composition with different combinations of pharmaceutical active ingredients, hydrophilic surfactant, lipophilic surfactants and triglycerides.
U.S. Patent No. 4,590,062 discloses a compressed product containing an active produced by dry blending with a matrix combination of a hydrophobic polymer (e.g. ethylcellulose) and a wax, fatty acid, neutral lipid or combination thereof.
U.S. Patent Application No. US 20090004281 discloses a modified release multiparticulate osmotic delivery system for oral administration. The composition includes an osmotic subcoat applied to core that includes at least one drug in combination with at least one pharmaceutically acceptable excipient.
U.S. Patent Application No. US 20080131501 discloses a pharmaceutical composition which provides enhanced immediate release formulations of topiramate, in which 80% of the active ingredient is released in the period of time of not more than 30 min.
There exists an enduring need to develop an improved and simple modified release pharmaceutical composition of topiramate which will provide an alternative to existing formulations for treatment of epileptic conditions over a 24 hour period and simultaneously may reduce or eliminate the side effects associated with peaking and fluctuating plasma levels of the drug.
The inventors of the present invention have surprisingly found that by using two different types of components of topiramate in the composition, at least one of it
being in the form of a matrix of topiramate and release modifying substances, the resulting composition may exhibit release of topiramate over a 24 hour period and/or reduce or eliminate the side effects associated with peaking and fluctuating plasma levels of topiramate.
The composition of the present invention relates to modified release pharmaceutical compositions comprising at least two types of components, wherein at least one type of the component comprises a matrix of topiramate or salts thereof and one or more release modifying substances. The component of the composition comprising said matrix exhibits sustained release of topiramate or salts thereof. The composition may provide extended and specific release of topiramate or salts thereof to achieve therapeutically effective plasma concentration over a period of 24 hours to treat epileptic conditions when administered to a patient in need thereof.
Summary of the Invention
In one general aspect, there is provided a modified release pharmaceutical composition comprising at least two types of components, each comprising topiramate or salts thereof, wherein at least one type of the component comprises a matrix of topiramate or salts thereof with one or more release modifying substances and optionally one or more pharmaceutically acceptable excipients.
In another general aspect, there is provided a modified release pharmaceutical composition comprising at least two types of components, each comprising topiramate or salts thereof, wherein at least one type of the component is uncoated and comprises a matrix of topiramate or salts thereof with one or more release modifying substances.
In another general aspect, there is provided a modified release pharmaceutical composition comprising at least two types of components, each comprising topiramate or salts thereof, wherein at least one type of the component comprises a matrix of topiramate or salts thereof with one or more release modifying substances and it exhibits sustained release of topiramate or salts thereof.
In another general aspect, there is provided a modified release pharmaceutical composition comprising at least two types of components, each comprising topiramate or salts thereof, wherein at least one type of the component comprises a matrix of topiramate or salts thereof with one or more release modifying substances and dimension of at least one type of the component is more than 1 .0 mm.
In another general aspect, there is provided a modified release pharmaceutical composition comprising at least two types of components, each comprising topiramate or salts thereof, wherein at least one type of the component comprises a matrix of topiramate or salts thereof with one or more release modifying substances comprises ethyl cellulose, methacrylic acid copolymer, hydroxypropyl cellulose or hydroxypropyl methylcellulose, bees wax, carnauba wax or combination thereof.
In another general aspect, there is provided a modified release pharmaceutical composition comprising at least two types of components, each comprising topiramate or salts thereof exhibits sustained release of topiramate or salts thereof, wherein the first type of the component comprises a matrix of topiramate or salts thereof with one or more release modifying substances and the second type of component exhibits either immediate release or sustained release of topiramate or salts thereof.
In another general aspect, there is provided a modified release pharmaceutical composition comprising at least two types of components, each comprising topiramate or salts thereof, wherein first type of the component comprises a matrix of topiramate or salts thereof with one or more release modifying substances and the second type of the component is coated with one or more hydrophilic and/or hydrophobic coating substances. The hydrophobic release controlling substances, preferably polymers are pH dependent or pH independent.
In another general aspect, there is provided a modified release pharmaceutical composition comprising at least two types of components, each comprising topiramate or salts thereof, wherein the first type of the component comprises a matrix of topiramate or salts thereof with one or more release modifying substances and the second type of component is coated with about 1 % to 70% w/w of hydrophilic or hydrophobic coating substances by total weight of another component.
In another general aspect, there is provided a modified release pharmaceutical composition comprising at least two types of components, each comprising topiramate or salts thereof, wherein at least one type of the component comprises a matrix of topiramate or salts thereof with one or more release modifying substances and the components are in the form of pellets, granules, compressed units or combination thereof.
In another general aspect, there is provided a modified release pharmaceutical composition comprising at least two types of components, each comprising topiramate or salts thereof, wherein at least one type of the component is in the form of pellets and comprises a matrix of topiramate or salts thereof with one or more release modifying substances.
In another general aspect, there is provided a modified release pharmaceutical composition comprising at least two types of components, each comprising topiramate or salts thereof, wherein the first type of the component comprises a matrix of topiramate or salts thereof with one or more release modifying substances and the second type of the component comprises inert carriers, preferably in the form of cores, are sequentially coated with one or more topiramate and rate modifying polymer layers at different levels.
The inert carrier used in the present invention includes, but are not limited to, a group consisting of cellulose spheres, silicon dioxide, starch and sugar spheres. The amount of the inert carrier in the composition ranges from about 20% to about 95% w/w, and preferably from about 30% to about 90% w/w of the composition.
Topiramate is introduced to the inert carrier by techniques known to one skilled in the art such as drug layering, powder coating, extrusion/spheronization, roller compaction or dry/wet granulation. Preferably, the introduction method is drug layering by spraying a suspension of topiramate and a binder onto the inert carrier.
In another general aspect, there is provided a modified release pharmaceutical composition comprising at least two types of components, each comprising topiramate or salts thereof, wherein at least one type of the component comprises a matrix of topiramate or salts thereof with one or more release modifying substances and exhibits release of more than 80% of topiramate or salts thereof within a period of 24 hours, preferably 16 hours and more preferably 8 hours.
In another general aspect, there is provided a process of preparing the modified release pharmaceutical composition, which process comprises the steps of:
(a) mixing topiramate and one or more release modifying substances, optionally with one or more pharmaceutical excipients;
(b) granulating the mixture prepared in step (a) to form topiramate extended release components,
(c) optionally, lubricating the topiramate extended release components;
(d) mixing topiramate with one or more pharmaceutical excipients;
(e) granulating the mixture prepared in step (d) to form topiramate immediate release components;
(f) optionally, lubricating the topiramate immediate release components, and
(g) filling the topiramate extended and immediate release components in capsule.
In another general aspect, there is provided a modified release pharmaceutical composition comprising at least two types of components, each comprising topiramate or salts thereof, wherein at least one type of the component comprises a matrix of topiramate or salts thereof with one or more release modifying substances and the dosage form retains at least 90% w/w of the potency of topiramate or salt thereof when stored at 40°C and 60% relative humidity for 3 months.
In another general aspect, there is provided a method of treating epileptic conditions by administering the patient in need thereof the modified release pharmaceutical composition of topiramate or salts thereof as substantially described throughout the specification.
Detailed Description of the Invention
The release modifying substances which can be used may be selected from the group consisting of hydrophilic agents (e.g. water-soluble polymers), lipophilic agents (water-insoluble polymers) and inert matrix agents, wherein the hydrophilic agents are selected from the group of pharmaceutical excipients
which generate a gel in contact with water, including cellulose derivatives such as hydroxypropyl methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose and the like; noncellulose polysaccharides such as galactomannanes, guar gum, carob gum, gum arabicum, alginates, pectins, and the like; polyvinylpyrrolidone; polyvinylacetate polymers and copolymers; acrylic acid polymers and copolymers, polyethylene oxide and mixtures thereof; the lipophilic agents are selected from the group consisting of waxes such as white wax, bees wax, carnauba wax and the like; fatty acids and alcohols such as stearic acid, palmitic acid, lauric acid and the like, and cetyl alcohol, cetostearyl alcohol, stearyl alcohol and the like; fatty acids esters such as monostearates of propylene glycol and fatty acid esters of sucrose, sucrose distearate and the like; and glycerides such as mono-, di- or triglycerides, e.g. palmitin, stearin, behenic, laurin, myristin, hydrogenated vegetable, castor, cottonseed oils, glyceril behenate and the like; ethyl cellulose; acrylic acid polymers and copolymers (available commercially under Eudragit® brand); and mixtures thereof; and the inert agents are selected from the group consisting of thermoplastic polymers, which are insoluble and indigestible in the gastrointestinal fluids, such as polyvinyl chloride, polyethylene, vinyl acetate/vinyl chloride copolymers, polymethylmethacrylates, polyamides, silicones, ethyl cellulose, polystyrene, and mixtures thereof.
The term "topiramate" used throughout the specification refers to not only topiramate per se, but also its other pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs and pharmaceutically acceptable prodrugs thereof.
The term "modified release" used throughout the specification shall apply to dosage forms, matrices, particles, coatings, portions thereof, or compositions that
alter the release of an active ingredient in any manner. Types of modified release include controlled, prolonged, sustained, extended, delayed, and the likes.
The term "matrix" used throughout the specification refers to the dispersion of drug within one or more release modifying substances and optionally one or more pharmaceutical excipients.
The term "component" used throughout the specification refers to mini-tablet, tablet, pellet, bead or granule prepared by standard methods known to the person skilled in the art, including but not limited to compression, granulation, spray coating, and extrusion/spheronization.
The term "pellets" used throughout the specification refers, but not limited to a carrier for pharmacologically active ingredients. Methods of manufacturing pellets for pharmaceutical use in both conventional (immediate release) and extended release single dosage forms include, but not limited to, extrusion/spheronization.
In one embodiment, the modified release pharmaceutical composition comprises at least two types of components, at least one type of the component, being uncoated, comprises a matrix of topiramate or salts thereof with one or more release modifying substances and optionally one or more pharmaceutically acceptable excipients.
In another embodiment, the release modifying substances comprises one or more of ethyl cellulose, methacrylic acid copolymer, hydroxypropyl cellulose or hydroxypropyl methylcellulose, bees wax, carnauba wax or combination thereof.
In another embodiment, the uncoated component comprising matrix of topiramate or salts thereof with one or more release modifying substances of the modified release pharmaceutical composition exhibits release of more than 80%
of topiramate or salts thereof within a period of 24 hours, preferably 16 hours and more preferably 8 hours
In another embodiment, the dimension of at least one type of the component is more than 1 .0 mm.
In another embodiment, the modified release pharmaceutical composition comprising at least two types of components, one comprising matrix of topiramate or salts thereof and one or more release modifying substances that exhibits sustained release and the second type of component exhibits either immediate release or sustained release of topiramate or salts thereof.
In another embodiment, the second type of component of the modified release pharmaceutical composition is coated with one or more hydrophilic and/or hydrophobic coating substances.
In another embodiment, another type of component of the modified release pharmaceutical composition is coated with about 1 % to 70%w/w of hydrophilic or hydrophobic coating substances by total weight of another component.
In another embodiment, the components in the modified release pharmaceutical composition are in the form of one or more pellets, granules, compressed units (e.g. tablets, mini-tablets) or combination thereof.
In another embodiment, the modified release pharmaceutical composition in accordance with the present invention retains at least 90% w/w of the potency of topiramate or salt thereof when stored at 25°C and 40% relative humidity or at 40°C and 25% relative humidity for 3 months.
The modified release composition of the present invention can be prepared by methods known to the person skilled in the art. Preferably, the composition
comprises plurality of uncoated units. The uncoated units can be prepared by various methods known to the person skilled in the art, such as extrusion, wet granulation, and dry granulation, followed by compression or slugging.
In an embodiment, the process of preparing the modified release pharmaceutical composition comprises steps of:
(a) mixing topiramate and one or more release modifying substances, optionally with one or more pharmaceutical excipients;
(b) granulating the mixture prepared in step (a) to form topiramate extended release components,
(c) optionally, lubricating the topiramate extended release components;
(d) mixing topiramate with one or more pharmaceutical excipients;
(e) granulating the mixture prepared in step (d) to form topiramate immediate release components;
(f) optionally, lubricating the topiramate immediate release components, and
(g) filling the topiramate extended and immediate release components in capsule.
The modified release pharmaceutical composition of the present invention may be developed in the form a capsule, a tablet, a caplet and a mini-tablet. Preferably the dosage form is in the form of a capsule.
The composition of the present invention may comprise one or more pharmaceutically acceptable excipients selected from, but not limited to, diluent, binder, disintegrant, glidant, lubricant, stabilizing agent, and flavoring agents.
The term "pharmaceutically acceptable excipients" includes a pharmaceutically acceptable material, composition or vehicle, suitable for administering an active pharmaceutical ingredient. Each excipient should be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not injurious to
the patient. Excipients include diluents, binders, disintegrants, glidants, lubricants, flavoring, and others.
Diluents increase the bulk of a solid pharmaceutical composition. Exemplary diluents for solid compositions include, but are not limited to, microcrystalline cellulose, microfine cellulose, lactose, starch, pregelatinized starch, calcium carbonate, calcium sulfate, sugar, dextrates, dextrin, dextrose, dibasic calcium phosphate dihydrate, tribasic calcium phosphate, kaolin, magnesium carbonate, magnesium oxide, maltodextrin, mannitol, polymethacrylates, potassium chloride, powdered cellulose, sodium chloride, sorbitol and talc.
Solid pharmaceutical compositions that are compressed may include excipients whose functions include helping to bind the active ingredient and other excipients together after compression. Exemplary binders for solid pharmaceutical compositions include, but are not limited to, acacia, alginic acid, carbomer, carboxymethylcellulose sodium, dextrin, ethyl cellulose, gelatin, guar gum, hydrogenated vegetable oil, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, liquid glucose, magnesium aluminum silicate, maltodextrin, methylcellulose, polymethacrylates, povidone, pregelatinized starch, sodium alginate and starch.
Disintegrants increase the dissolution rate of a compacted solid pharmaceutical composition in the patient's stomach, for example. Exemplary disintegrants include, but are not limited to, alginic acid, carboxymethylcellulose calcium, carboxymethylcellulose sodium, colloidal silicon dioxide, croscarmellose sodium, crospovidone, guar gum, magnesium aluminum silicate, methyl cellulose, microcrystalline cellulose, polacrilin potassium, powdered cellulose, pregelatinized starch, sodium alginate, sodium starch glycolate and starch.
Glidants can be added to improve the flowability of a non-compacted solid composition and to improve the accuracy of dosing. Exemplary excipients that
may function as glidants include, but not limited to, colloidal silicon dioxide, magnesium trisilicate, powdered cellulose, starch, talc and tribasic calcium phosphate.
A lubricant can be added to the composition to reduce adhesion and ease the release of the product from the dye. Exemplary lubricants include, but are not limited to, magnesium stearate, calcium stearate, glyceryl monostearate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, mineral oil, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, sodium stearyl fumarate, stearic acid, talc and zinc stearate.
The present invention further provides a method of treating epileptic conditions by administering the patient in need thereof the modified release composition of topiramate or salts thereof as substantially described throughout the specification.
The present invention is further illustrated by the following examples which are provided merely to be exemplary of the invention and do not limit the scope of the invention. Certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
Example 1 : Topiramate Extended Release Capsule
Table 1
Process: First (Extended release beads) component of topiramate was prepared by mixing topiramate, HPMC, polyvinylpyrrolidone, ethyl cellulose, methyl methacrylic acid methyl methacrylate polymer dispersion in a mixture of isopropyl alcohol and methylene dichloride. The mixture was granulated to form granules. The granules were then lubricated with magnesium stearate.
The second component (Immediate release pellets) was formed by dispersing topiramate in hydroxypropyl methylcellulose solution that contains vitamin E TPGS, Polyoxyl hydrogenated castor oil and sodium lauryl sulfate. The resulting
dispersion was then sprayed on to sugar spheres using a fluid bed processor to achieve a desired drug load.
The first (Extended release Beads) and second components (Immediate release Pellets) were then filled in to hard gelatin capsules.
Claims
1 . A modified release pharmaceutical composition comprising at least two types of components, each comprising topiramate or salts thereof, wherein at least one type of the component comprises a matrix of topiramate or salts thereof and one or more release modifying substances and optionally one or more pharmaceutically acceptable excipients.
2. The modified release pharmaceutical composition of claim 1 , wherein at least one type of the component is uncoated.
3. The modified release pharmaceutical composition of claim 1 , wherein the release modifying substance comprises one or more of ethyl cellulose, methacrylic acid copolymer, hydroxypropyl cellulose or hydroxypropyl methylcellulose, bees wax, carnauba wax or combination thereof.
4. The modified release pharmaceutical composition of claim 1 , wherein the components comprising a matrix of topiramate or salts thereof and one or more release modifying substances exhibits sustained release of topiramate or salts thereof.
5. The modified release pharmaceutical composition of claim 1 , wherein the composition comprises first type of components that comprises a matrix of topiramate or salts thereof and one or more release modifying substances and second type of components that exhibits either immediate release or sustained release of topiramate or salts thereof.
6. The modified release pharmaceutical composition of claim 5, wherein said second type of components does not comprise matrix of topiramate or salts thereof and one or more release modifying substances.
7. The modified release pharmaceutical composition of claim 1 or 5, wherein the components are in the form of pellets, granules, compressed units or combinations thereof.
8. The modified release pharmaceutical composition of claim 1 or 5, wherein dimension of the components is more than 1 .0 mm.
9. The modified release pharmaceutical composition of claim 5, wherein the second type of the component comprises inert carriers which are sequentially coated with one or more topiramate and rate modifying polymer layers.
10. The modified release pharmaceutical composition of claim 5, wherein said second type of the components is coated with one or more layers of hydrophilic or hydrophobic polymers.
1 1 . The modified release pharmaceutical composition of claim 10, wherein hydrophilic or hydrophobic polymers are pH dependent or pH independent.
12. The modified release pharmaceutical composition of claim 10, wherein said second type of the components are coated with about 1 % to about 70% w/w of the hydrophilic or hydrophobic polymers by total weight of the first type of component.
13. The modified release pharmaceutical composition of claim 1 or 5, wherein the components releases more than 80% of topiramate or salts thereof in a period of 24 hours, preferably in 16 hours and more preferably in 8 hours.
14. A process of preparing the modified release pharmaceutical composition, which process comprises the steps of:
(a) mixing topiramate and one or more release modifying substances, optionally with one or more pharmaceutical excipients;
(b) granulating the mixture prepared in step (a) to form topiramate extended release components,
(c) optionally, lubricating the topiramate extended release components;
(d) mixing topiramate with one or more pharmaceutical excipients;
(e) granulating the mixture prepared in step (d) to form topiramate immediate release components;
(f) optionally, lubricating the topiramate immediate release components, and
(g) filling the topiramate extended and immediate release components in a capsule.
15. A method of treating epileptic conditions by administering the patient in need thereof the modified release composition of claim 1 or 5.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN1156/MUM/2013 | 2013-03-26 | ||
| IN1157/MUM/2013 | 2013-03-26 | ||
| IN1156MU2013 IN2013MU01156A (en) | 2013-03-26 | 2014-03-22 | |
| IN1157MU2013 IN2013MU01157A (en) | 2013-03-26 | 2014-03-22 |
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| WO2014167439A1 true WO2014167439A1 (en) | 2014-10-16 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110638791A (en) * | 2019-10-31 | 2020-01-03 | 浙江普利药业有限公司 | Topiramate sustained-release capsule and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110638791A (en) * | 2019-10-31 | 2020-01-03 | 浙江普利药业有限公司 | Topiramate sustained-release capsule and preparation method thereof |
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