WO2013077829A1 - Water-soluble pharmaceutical granules - Google Patents

Water-soluble pharmaceutical granules Download PDF

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Publication number
WO2013077829A1
WO2013077829A1 PCT/TR2012/000196 TR2012000196W WO2013077829A1 WO 2013077829 A1 WO2013077829 A1 WO 2013077829A1 TR 2012000196 W TR2012000196 W TR 2012000196W WO 2013077829 A1 WO2013077829 A1 WO 2013077829A1
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Prior art keywords
water
soluble pharmaceutical
formulations
pharmaceutical granule
formulations according
Prior art date
Application number
PCT/TR2012/000196
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French (fr)
Inventor
Mahmut Bilgic
Original Assignee
Mahmut Bilgic
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Publication of WO2013077829A1 publication Critical patent/WO2013077829A1/en

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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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches

Definitions

  • the present invention relates to water-soluble granule formulations appropriate for oral use which comprise montelukast sodium as active agent; and to the production method and fields of use thereof.
  • the present invention relates to water-soluble granule formulations comprising montelukast sodium as active agent in order to be used for the prevention and/or treatment of allergic and inflammatory diseases of upper and lower respiratory tract or skin such as seasonal allergic rhinitis, perennial allergic rhinitis, allergic sinusitis, atopic dermatitis, urticaria, allergic asthma, aspirin-induced asthma , exercise-induced asthma, nasal polyps, chronic obstructive pulmonary disease (COPD), conjunctivitis, rhino-conjunctivitis, bronchitis.
  • allergic and inflammatory diseases of upper and lower respiratory tract or skin such as seasonal allergic rhinitis, perennial allergic rhinitis, allergic sinusitis, atopic dermatitis, urticaria, allergic asthma, aspirin-induced asthma , exercise-induced asthma, nasal polyps, chronic obstructive pulmonary disease (COPD), conjunctivitis, rhino-conjunctivitis, bronchitis.
  • Montelukast is a leukotriene receptor antagonist, chemical name of which is l-[[[(lR)-l-[3- [(lE)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(l-hydroxy-l-methyl- ethyl)phenyl]propyl]thio]metyl]cyclopropane-acetic acid (Formula I).
  • Montelukast was firstly described in the patent numbered EP480717 Al .
  • Montelukast which is generally used as sodium salt, is a leukotriene receptor antagonist approved in the treatment of asthma in adults and pediatric patients over 2 years old.
  • the product marketed under the trademark SINGULAIR® is in dosage forms of film tablet
  • An oral granule form of the product is also present to be used in pediatric patients aged between 6 months to 2 years.
  • montelukast sodium is a sensitive active agent that can easily degrade being affected by factors such as light, moisture, heat.
  • Hygroscopic structure of the active agent constitutes an important obstacle particularly in the production of water-soluble formulations.
  • the prior art suggests various solutions for this problem of the active agent.
  • the patent numbered WO/2003/035036 relates to a granule formulation comprising an effective amount of montelukast sodium and to the production method thereof.
  • the formulation is prepared by spraying the solution comprising montelukast sodium onto a diluent and treating it with a lubricant.
  • the present invention relates to water-soluble granule formulations comprising montelukast sodium as active agent; and to the production method and fields of use thereof.
  • the water-soluble granule formulations of the invention comprise montelukast as active agent at least at 20%, preferably in the range of 0.5% to 15%, more preferably in the range of 0.5% to 10%, even more preferably in the range of 0.5% to 5% in proportion to the total weight of the formulation.
  • a characteristic of the granule formulations of the invention is that said formulations comprise montelukast sodium as active agent and at least one pharmaceutically acceptable excipient.
  • a characteristic of the water-soluble granule formulations of the invention is that the types of excipients used in the formulations are limited so that a possible degradation caused by active agent-excipient interaction is prevented.
  • a characteristic of the water-soluble granule formulations of the invention is that said formulations comprise montelukast sodium as active agent and at least one excipient selected from a group comprising diluent, disintegrant, binder and solvent/solvent mixtures or combinations thereof.
  • the diluents that can be comprised in the water-soluble granule formulations of the invention can be selected from a group comprising calcium carbonate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulphate, dextrose, fructose, lactitol, magnesium carbonate, magnesium oxide, maltitol, maltodextrin, maltose, simethicone, sorbitol, sodium chloride, sucrose, talc, xylitol or combinations thereof.
  • the disintegrants that can be comprised in the water-soluble granule formulations of the invention can be selected from a group comprising carboxymethyl cellulose, carboxymethyl cellulose calcium, carboxymethyl cellulose sodium, croscarmellose sodium, crospovidone, hydroxypropyl cellulose, microcrystalline cellulose, methyl cellulose, chitosan, starch, sodium starch glycolate or combinations thereof.
  • the binders that can be comprised in the water-soluble granule formulations of the invention can be selected from a group comprising carboxymethyl cellulose sodium, ethyl cellulose, gelatin, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminium silicate, maltodextrin, methyl cellulose, povidone, starch or combinations thereof.
  • the solvents that can be comprised in the water-soluble granule formulations of the invention can be selected from a group comprising deionized water, toluene, benzene, acetone, methyl acetate, tetrahydrofurane, heptane, hexane, acetonitrile, alcohols such as ethyl alcohol, methyl alcohol and/ or combinations thereof.
  • a characteristic of the water-soluble granule formulations of the invention is that said formulations comprise montelukast sodium as active agent and at least one pharmaceutically acceptable diluent and at least one pharmaceutically acceptable solvent as excipients.
  • a characteristic of the water-soluble granule formulations of the invention is that said formulations comprise sorbitol as diluent in the range of 85% to 99.5% in proportion to the total weight of the formulation.
  • a characteristic of the water-soluble granule formulations of the invention is that said formulations comprise sorbitol as diluent in the range of 90% to 99.5% in proportion to the total weight of the formulation.
  • a characteristic of the water-soluble granule formulations of the invention is that said formulations comprise sorbitol as diluent in the range of 95% to 99.5% in proportion to the total weight of the formulation.
  • the present invention also provides a method for the production of water-soluble granule formulations.
  • the water-soluble granule formulations of the invention can be produced by one of the wet granulation or dry granulation methods. However, as differs from the prior art, the granule formulations of the invention was able to be produced by wet granulation method without any degradation caused by the hygroscopic structure of the active agent.
  • the granule formulations of the invention can be produced in any dosage form suitable for oral use.
  • the oral dosage forms of the invention can be tablet, capsule, sachet forms.
  • the water-soluble granule formulations of the invention can optionally be compressed into tablets or filled into capsules or one-dose packs such as bottles or sachets to be used after diluted.
  • the water-soluble granule formulations of the invention are preferably in sachet dosage form.
  • the preferred production method for the water-soluble granule formulations of the invention is wet granulation method which is basically applied as follows:
  • the granulation solution used in the preparation of water-soluble granules of the invention can comprise sorbitol as diluent in addition to deionized water and a pharmaceutically acceptable solvent.
  • sorbitol used as diluent in the formulations can be used in the granulation solution in the first step, whereas the other part of it is used in the active agent mixture in the second step.
  • the water-soluble granule formulations of the invention can be combined with a second active agent.
  • At least one antihistaminic can be used as the second active agent.
  • Antihistaminics that can be used in the formulations of the invention are selected from a group comprising diphenhydramine, dimenhydrinate, carbinoxamine, chlorphenoxamine, mepyramine, antazoline, tripelamin, dexchlorpheniramine, dexbrompheniramine, pheniramine, buclizine, hydroxyzine, cinnarizine, meclizine, alimemazine, promethazine, cyproheptadine, ebastine, astemizole, acrivastine, loratadine, desloratadine, ketotifen, cetirizine, levocetirizine or pharmaceutically acceptable salts, solvates, derivatives, polymorphs, hydrates, enantiomers or combinations thereof.
  • the preferred second active agent in the formulations of the invention is desloratadine.
  • the amount of the second active agent that can be used in the formulations of the invention is in the range of 0.1 to 5%, preferably in the range of 0.1 to 4%, more preferably in the range of 0.1 to 3%, even more preferably in the range of 0.1 to 2% in proportion to the total weight of the formulation.
  • a characteristic of the water-soluble granule formulations of the invention is that said formulations comprise a second active agent in the range of 0.1 to 5%, preferably in the range of 0.1 to 4%, more preferably in the range of 0.1 to 3%, even more preferably in the range of 0.1 to 2% in proportion to the total weight of the formulation.
  • Dosage forms for combined treatment can be taken separately, simultaneously or consecutively; while they can also be taken by combining montelukast with the other said active agent or agents in a single dosage form.
  • the preferred dosage form is prepared by formulating the two active agents together and combining them in the same dosage form.
  • the preferred production method here is wet granulation method, which is applied as described in detail above.
  • the second active agent is preferably used in the granulation solution composition.
  • the water-soluble granule formulations of the invention is used in the prevention and/or treatment of allergic and inflammatory diseases of upper and lower respiratory tract and the skin such as seasonal allergic rhinitis, perennial allergic rhinitis, allergic sinusitis, atopic dermatitis, urticaria, allergic asthma, aspirin-induced asthma, exercise-induced asthma, nasal polyps, chronic obstructive pulmonary disease (COPD), conjunctivitis, rhino-conjunctivitis, bronchitis; and for relieving symptoms associated with these diseases.
  • allergic and inflammatory diseases of upper and lower respiratory tract and the skin such as seasonal allergic rhinitis, perennial allergic rhinitis, allergic sinusitis, atopic dermatitis, urticaria, allergic asthma, aspirin-induced asthma, exercise-induced asthma, nasal polyps, chronic
  • Example 2 Sachet Formulation Comprising Montelukast Sodium and Desloratadine
  • Formulations to be produced according to the formulations given above are prepared by the wet granulation method explained in detail in the description of the invention; and brought into use in sachet form after filled into one-dose packs.

Abstract

The present invention relates to water-soluble granule formulations which are appropriate for oral use and comprise montelukast sodium as active agent; and to the production method and fields of use thereof.

Description

WATER-SOLUBLE PHARMACEUTICAL GRANULES
The present invention relates to water-soluble granule formulations appropriate for oral use which comprise montelukast sodium as active agent; and to the production method and fields of use thereof. The Prior Art
The present invention relates to water-soluble granule formulations comprising montelukast sodium as active agent in order to be used for the prevention and/or treatment of allergic and inflammatory diseases of upper and lower respiratory tract or skin such as seasonal allergic rhinitis, perennial allergic rhinitis, allergic sinusitis, atopic dermatitis, urticaria, allergic asthma, aspirin-induced asthma , exercise-induced asthma, nasal polyps, chronic obstructive pulmonary disease (COPD), conjunctivitis, rhino-conjunctivitis, bronchitis.
Montelukast is a leukotriene receptor antagonist, chemical name of which is l-[[[(lR)-l-[3- [(lE)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(l-hydroxy-l-methyl- ethyl)phenyl]propyl]thio]metyl]cyclopropane-acetic acid (Formula I).
Figure imgf000002_0001
Formula (I): Montelukast
Montelukast was firstly described in the patent numbered EP480717 Al . Montelukast, which is generally used as sodium salt, is a leukotriene receptor antagonist approved in the treatment of asthma in adults and pediatric patients over 2 years old.
The product marketed under the trademark SINGULAIR® is in dosage forms of film tablet
(comprising 10 mg montelukast sodium) and chewing tablet (comprising 4 mg and 5 mg montelukast sodium). An oral granule form of the product is also present to be used in pediatric patients aged between 6 months to 2 years.
However, it is known that montelukast sodium is a sensitive active agent that can easily degrade being affected by factors such as light, moisture, heat. Hygroscopic structure of the active agent constitutes an important obstacle particularly in the production of water-soluble formulations. The prior art suggests various solutions for this problem of the active agent.
The patent numbered WO/2003/035036 relates to a granule formulation comprising an effective amount of montelukast sodium and to the production method thereof. In the production method of the invention, the formulation is prepared by spraying the solution comprising montelukast sodium onto a diluent and treating it with a lubricant.
The patent numbered US2007184108 discloses montelukast sodium formulations which are produced by wet granulation method and do not comprise microcrystalline cellulose. Said patent mentions that use of microcrystalline cellulose in montelukast sodium formulations causes a serious increase in sulphoxide impurity in the formulations. When the prior art is considered, there is a need for new approaches for water-soluble formulations comprising montelukast sodium.
As a result of the studies conducted on water-soluble montelukast sodium formulations, the inventor has discovered that there is a degradation in the formulations seen with the important increase in Des-montelukast impurity which is one of the important degradation products of montelukast sodium and has the chemical structure given below with Formula (II).
Figure imgf000003_0001
Formula (II): Des-montelukast
This problem was solved with the new water-soluble granule formulations produced within the scope of the present invention. Detailed Description of the Invention
The present invention relates to water-soluble granule formulations comprising montelukast sodium as active agent; and to the production method and fields of use thereof.
The water-soluble granule formulations of the invention comprise montelukast as active agent at least at 20%, preferably in the range of 0.5% to 15%, more preferably in the range of 0.5% to 10%, even more preferably in the range of 0.5% to 5% in proportion to the total weight of the formulation.
A characteristic of the granule formulations of the invention is that said formulations comprise montelukast sodium as active agent and at least one pharmaceutically acceptable excipient.
A characteristic of the water-soluble granule formulations of the invention is that the types of excipients used in the formulations are limited so that a possible degradation caused by active agent-excipient interaction is prevented.
A characteristic of the water-soluble granule formulations of the invention is that said formulations comprise montelukast sodium as active agent and at least one excipient selected from a group comprising diluent, disintegrant, binder and solvent/solvent mixtures or combinations thereof.
The diluents that can be comprised in the water-soluble granule formulations of the invention can be selected from a group comprising calcium carbonate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulphate, dextrose, fructose, lactitol, magnesium carbonate, magnesium oxide, maltitol, maltodextrin, maltose, simethicone, sorbitol, sodium chloride, sucrose, talc, xylitol or combinations thereof.
The disintegrants that can be comprised in the water-soluble granule formulations of the invention can be selected from a group comprising carboxymethyl cellulose, carboxymethyl cellulose calcium, carboxymethyl cellulose sodium, croscarmellose sodium, crospovidone, hydroxypropyl cellulose, microcrystalline cellulose, methyl cellulose, chitosan, starch, sodium starch glycolate or combinations thereof. The binders that can be comprised in the water-soluble granule formulations of the invention can be selected from a group comprising carboxymethyl cellulose sodium, ethyl cellulose, gelatin, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminium silicate, maltodextrin, methyl cellulose, povidone, starch or combinations thereof.
The solvents that can be comprised in the water-soluble granule formulations of the invention can be selected from a group comprising deionized water, toluene, benzene, acetone, methyl acetate, tetrahydrofurane, heptane, hexane, acetonitrile, alcohols such as ethyl alcohol, methyl alcohol and/ or combinations thereof. A characteristic of the water-soluble granule formulations of the invention is that said formulations comprise montelukast sodium as active agent and at least one pharmaceutically acceptable diluent and at least one pharmaceutically acceptable solvent as excipients.
As a result of the development studies conducted, the inventor has discovered that the type and the amount of the diluent used in water-soluble granule formulations comprising montelukast sodium play an important role in providing formulation stability.
The studies conducted show that use of sorbitol at least at 80% in proportion to the total weight of the formulation in the water-soluble granule formulations leads to an important decrease in the amount of des-montelukast impurity which is one of the degradation products of the active agent. A characteristic of the water-soluble granule formulations of the invention is that said formulations comprise sorbitol as diluent in the range of 85% to 99.5% in proportion to the total weight of the formulation.
A characteristic of the water-soluble granule formulations of the invention is that said formulations comprise sorbitol as diluent in the range of 90% to 99.5% in proportion to the total weight of the formulation.
A characteristic of the water-soluble granule formulations of the invention is that said formulations comprise sorbitol as diluent in the range of 95% to 99.5% in proportion to the total weight of the formulation. The present invention also provides a method for the production of water-soluble granule formulations.
The water-soluble granule formulations of the invention can be produced by one of the wet granulation or dry granulation methods. However, as differs from the prior art, the granule formulations of the invention was able to be produced by wet granulation method without any degradation caused by the hygroscopic structure of the active agent.
The granule formulations of the invention can be produced in any dosage form suitable for oral use.
The oral dosage forms of the invention can be tablet, capsule, sachet forms. In other words, the water-soluble granule formulations of the invention can optionally be compressed into tablets or filled into capsules or one-dose packs such as bottles or sachets to be used after diluted.
The water-soluble granule formulations of the invention are preferably in sachet dosage form.
The preferred production method for the water-soluble granule formulations of the invention is wet granulation method which is basically applied as follows:
1. Preparing the granulation solution by mixing a pharmaceutically acceptable solvent, deionized water.
2. Preparing the active agent mixture by mixing montelukast sodium and the diluent,
3. Wet granulating the active agent mixture obtained in the second step with the granulation solution obtained in the first step,
4. Drying and sieving the obtained granules. Obtaining the dosage form by optionally compressing this final granule mixture into tablets, filling them into bottles, sachets or capsules.
The granulation solution used in the preparation of water-soluble granules of the invention can comprise sorbitol as diluent in addition to deionized water and a pharmaceutically acceptable solvent. In other words, one part of sorbitol used as diluent in the formulations can be used in the granulation solution in the first step, whereas the other part of it is used in the active agent mixture in the second step.
The water-soluble granule formulations of the invention can be combined with a second active agent. At least one antihistaminic can be used as the second active agent.
Antihistaminics that can be used in the formulations of the invention are selected from a group comprising diphenhydramine, dimenhydrinate, carbinoxamine, chlorphenoxamine, mepyramine, antazoline, tripelamin, dexchlorpheniramine, dexbrompheniramine, pheniramine, buclizine, hydroxyzine, cinnarizine, meclizine, alimemazine, promethazine, cyproheptadine, ebastine, astemizole, acrivastine, loratadine, desloratadine, ketotifen, cetirizine, levocetirizine or pharmaceutically acceptable salts, solvates, derivatives, polymorphs, hydrates, enantiomers or combinations thereof. The preferred second active agent in the formulations of the invention is desloratadine.
The amount of the second active agent that can be used in the formulations of the invention is in the range of 0.1 to 5%, preferably in the range of 0.1 to 4%, more preferably in the range of 0.1 to 3%, even more preferably in the range of 0.1 to 2% in proportion to the total weight of the formulation.
In other words, a characteristic of the water-soluble granule formulations of the invention is that said formulations comprise a second active agent in the range of 0.1 to 5%, preferably in the range of 0.1 to 4%, more preferably in the range of 0.1 to 3%, even more preferably in the range of 0.1 to 2% in proportion to the total weight of the formulation.
Dosage forms for combined treatment can be taken separately, simultaneously or consecutively; while they can also be taken by combining montelukast with the other said active agent or agents in a single dosage form. In the combined product of the invention, the preferred dosage form is prepared by formulating the two active agents together and combining them in the same dosage form.
The preferred production method here is wet granulation method, which is applied as described in detail above. In the given production method, the second active agent is preferably used in the granulation solution composition. The water-soluble granule formulations of the invention is used in the prevention and/or treatment of allergic and inflammatory diseases of upper and lower respiratory tract and the skin such as seasonal allergic rhinitis, perennial allergic rhinitis, allergic sinusitis, atopic dermatitis, urticaria, allergic asthma, aspirin-induced asthma, exercise-induced asthma, nasal polyps, chronic obstructive pulmonary disease (COPD), conjunctivitis, rhino-conjunctivitis, bronchitis; and for relieving symptoms associated with these diseases.
The following examples are given to explain the pharmaceutical compositions of the invention and the preparation methods thereof; the scope of the invention cannot be limited to these examples.
Example 1: Montelukast Sodium Sachet Formulation
Figure imgf000009_0001
q.s. ^quantum sufflcit
Example 2: Sachet Formulation Comprising Montelukast Sodium and Desloratadine
Figure imgf000009_0002
q.s. *quantum sufficit Example 3. Production Method
Formulations to be produced according to the formulations given above are prepared by the wet granulation method explained in detail in the description of the invention; and brought into use in sachet form after filled into one-dose packs.

Claims

1. Water-soluble pharmaceutical granule formulations comprising montelukast.
2. The water-soluble pharmaceutical granule formulations according to claim 1, characterized in that said formulations comprise montelukast sodium at least at 20% by weight.
3. The water-soluble pharmaceutical granule formulations according to claims 1 and 2, characterized in that said formulations comprise montelukast sodium in the range of 0.5 to 15% by weight.
4. The water-soluble pharmaceutical granule formulations according to claims 1 to 3, characterized in that said formulations comprise montelukast sodium in the range of 0.5 to 10% by weight.
5. The water-soluble pharmaceutical granule formulations according to claims 1 to 4, characterized in that said formulations comprise montelukast sodium in the range of 0.5 to 5% by weight.
6. The water-soluble pharmaceutical granule formulations according to any one of the preceding claims, characterized in that said formulations comprise at least one pharmaceutically acceptable excipient.
7. The water-soluble pharmaceutical granule formulations according to claim 6, characterized in that said formulations comprise at least one excipient selected from a group comprising at least one diluent, at least one disintegrant, at least one binder and at least one solvent or combinations thereof.
8. The water-soluble pharmaceutical granule formulations according to claim 7, characterized in that said formulations comprise at least one pharmaceutically acceptable diluent and at least one pharmaceutically acceptable solvent as excipients.
9. The water-soluble pharmaceutical granule formulations according to claim 8, characterized in that the solvent that can be comprised in said formulations is selected from a group comprising deionized water, toluene, benzene, acetone, methyl acetate, tetrahydrofurane, heptane, hexane, acetonitrile, alcohols such as ethyl alcohol, methyl alcohol and/or combinations thereof.
10. The water-soluble pharmaceutical granule formulations according to claim 8, characterized in that the diluents that can be comprised in said formulations are selected from a group comprising calcium carbonate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulphate, dextrose, fructose, lactitol, magnesium carbonate, magnesium oxide, maltitol, maltodextrin, maltose, simethicone, sorbitol, sodium chloride, sucrose, talc, xylitol or combinations thereof.
11. The water-soluble pharmaceutical granule formulations according to claim 10, characterized in that said formulations comprise sorbitol as diluent at least at 80% in proportion to the total weight of the formulation.
12. The water-soluble pharmaceutical granule formulations according to claim 11, characterized in that said formulations comprise sorbitol as diluent in the range of 85 to 99.5% in proportion to the total weight of the formulation.
13. The water-soluble pharmaceutical granule formulations according to claims 1 1 and 12, characterized in that said formulations comprise sorbitol as diluent in the range of 90 to 99.5% in proportion to the total weight of the formulation.
14. The water-soluble pharmaceutical granule formulations according to claim 1 1 to 13, characterized in that said formulations comprise sorbitol as diluent in the range of 95 to 99.5% in proportion to the total weight of the formulation.
15. The production method of the water-soluble pharmaceutical granule formulations according to any one of the preceding claims, characterized in that said method is wet granulation method.
16. The water-soluble pharmaceutical granule formulations according to any one of the preceding claims, characterized in that said formulations are compressed into tablets or filled into capsules or one-dose packs such as bottles or sachets to be used after diluted.
17. The water-soluble pharmaceutical granule formulations according to claim 17, characterized in that said formulations are prepared in sachet dosage forms.
18. The water-soluble pharmaceutical granule formulations according to any one of the preceding claims, characterized in that said formulations are combined with at least one active agent.
19. The water-soluble pharmaceutical granule formulations according to claim 18, characterized in that the second active agent is selected from antihistaminic active agents comprising diphenhydramine, dimenhydrinate, carbinoxamine, chlorphenoxamine, mepyramine, antazoline, tripelamin, dexchlorpheniramine, dexbrompheniramine, pheniramine, buclizine, hydroxyzine, cinnarizine, meclizine, alimemazine, promethazine, cyproheptadine, ebastine, astemizole, acrivastine, loratadine, desloratadine, ketotifen, cetirizine, levocetirizine or pharmaceutically acceptable salts, solvates, derivatives, polymorphs, hydrates, enantiomers or combinations thereof.
20. The water-soluble pharmaceutical granule formulations according to claim 19, characterized in that the second active agent is desloratadine.
21. The water-soluble pharmaceutical granule formulations according to any one of the preceding claims, characterized in that said formulations are used in the prevention and/or treatment of allergic and inflammatory diseases of upper and lower respiratory tract or skin such as seasonal allergic rhinitis, perennial allergic rhinitis, allergic sinusitis, atopic dermatitis, urticaria, allergic asthma, aspirin-induced asthma, exercise-induced asthma, nasal polyps, chronic obstructive pulmonary disease (COPD), conjunctivitis, rhino-conjunctivitis, bronchitis.
PCT/TR2012/000196 2011-11-21 2012-11-16 Water-soluble pharmaceutical granules WO2013077829A1 (en)

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TR2011/11512 2011-11-21

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Cited By (2)

* Cited by examiner, † Cited by third party
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WO2019211159A1 (en) * 2018-05-02 2019-11-07 Ferring B.V. Improved pharmaceutical formulations
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