EP4175632A1 - A formulation comprising vildagliptin and at least one pharmaceutically acceptable excipient - Google Patents

A formulation comprising vildagliptin and at least one pharmaceutically acceptable excipient

Info

Publication number
EP4175632A1
EP4175632A1 EP21837553.3A EP21837553A EP4175632A1 EP 4175632 A1 EP4175632 A1 EP 4175632A1 EP 21837553 A EP21837553 A EP 21837553A EP 4175632 A1 EP4175632 A1 EP 4175632A1
Authority
EP
European Patent Office
Prior art keywords
sodium
vildagliptin
tablet formulation
formulation according
cellulose
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP21837553.3A
Other languages
German (de)
French (fr)
Other versions
EP4175632A4 (en
Inventor
Vildan TOMBAYOGLU
Arzu PALANTOKEN
Fatih Sunel
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sanovel Ilac Sanayi ve Ticaret AS
Original Assignee
Sanovel Ilac Sanayi ve Ticaret AS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sanovel Ilac Sanayi ve Ticaret AS filed Critical Sanovel Ilac Sanayi ve Ticaret AS
Publication of EP4175632A1 publication Critical patent/EP4175632A1/en
Publication of EP4175632A4 publication Critical patent/EP4175632A4/en
Pending legal-status Critical Current

Links

Classifications

    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2009—Inorganic compounds
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Definitions

  • the present invention relates to a tablet formulation comprising vildagliptin and at least one pharmaceutically acceptable excipient, so the formulation provides the desired stability and pharmacotechnical properties.
  • the present invention also relates to a simple, rapid, cost effective, time-saving and industrially convenient method of preparing the formulation comprising vildagliptin.
  • Diabetes mellitus is a group of disorders of carbohydrate metabolism in which the action of insulin is diminished or absent through altered secretion, decreased insulin activity or a combination of both factors.
  • Type 1 and Type 2 There are two main types of diabetes; Type 1 and Type 2:
  • Type 1 diabetes occurs because the insulin-producing cells of the pancreas (beta cells) are damaged. In Type 1 diabetes, the pancreas makes little or no insulin, so sugar cannot get into the body's cells for use as energy. People with Type 1 diabetes must use insulin injections to control their blood glucose.
  • Type 2 diabetes the pancreas makes insulin, but it either doesn't produce enough, or the insulin does not work properly. This diabetes occurs most often in people who are over 40 years old and overweight. Type 2 diabetes may sometimes be controlled with a combination of diet, weight management, and exercise. However, treatment also may include oral glucose-lowering medications or insulin injections.
  • Vildagliptin is a dipeptidyl dipeptidase-IV (DPP-IV) inhibitor developed for use in the treatment of type 2 diabetes (non-insulin dependent diabetes).
  • DPP-IV dipeptidyl dipeptidase-IV
  • vildagliptin inhibits the degradation of the dipeptidyl dipeptidase-IV enzyme, thereby inhibiting the effects of incretin hormones, glucagon-like peptide-1 (GLP-1), and of glucose-dependent insulinotropic peptide (GIP).
  • GLP-1 glucagon-like peptide-1
  • GIP glucose-dependent insulinotropic peptide
  • the chemical designation of vildagliptin is (S)- ⁇ [(3-hydroxyadamantan-1- yl)amino]acetyl ⁇ pyrrolidine-2-carbonitril, with the chemical structure illustrated below in Formula I.
  • Vildagliptin is an active agent that is highly-susceptible to air and humidity conditions. When vildagliptin is initially exposed to air and humidity, it degrades structurally and develops chemical behavioral changes. As a result of this, two main problems emerge. The first problem is that the stability of the products developed is not at a desired level and the shelf life thereof is shortened. Secondly, vildagliptin is reactive against the excipients employed in developing formulations. This fact causes impurities and unwanted components to be included into the formulation.
  • a further problem encountered while developing formulations comprising vildagliptin is flowability. Problems encountered in the flowability of vildagliptin make its production difficult.
  • the patent application WOOO/34241 discloses vildagliptin or an acid addition salt thereof, as well as their use in diabetes mellitus and obesity.
  • the patent application W02006/078593 claims a direct-compression formulation of a DPP-IV inhibitor compound, and preferably of vildagliptin or an acid addition salt thereof.
  • the patent application W02006/135723 discloses a formulation, comprising vildagliptin as an active agent, as well as hydroxypropyl methylcellulose, microcrystalline cellulose, and magnesium stearate.
  • the main object of the present invention is to provide a formulation comprising vildagliptin having pharmacotechnical properties such as flowability, compressibility and homogeneity.
  • Another object of the present invention is to provide a formulation comprising vildagliptin having desired stability without side reactions and chemical impurities.
  • a tablet formulation comprises;
  • colloidal silicone dioxide in the formulation wherein tablet is free of coating.
  • colloidal silicone dioxide is used, so while the formulation comprising vildagliptin is provided pharmacotechnical properties, especially, flowability. Also, certain amounts of excipients are used so while the stable formulation is provided without side reactions and chemical impurities.
  • the formulation has been developed by using standard techniques which is a simple and cost-effective method.
  • vildagliptin crystal form “Form A” is used in the tablet formulation.
  • the term “vildagliptin” refers to vildagliptin form A in the present invention.
  • Suitable fillers are selected from group comprising microcrystalline cellulose, lactose anhydrous, dicalcium phosphate dihydrate, ammonium alginate, calcium carbonate, calcium phosphate, calcium sulfate, cellulose, cellulose acetate, dextrates, dextrin, dextrose, erythritol, ethylcellulose, fructose, mannitol, magnesium carbonate, magnesium oxide, maltodextrin, polydextrose, polymethacrylates, sodium alginate, sodium chloride, sorbitol, starch, sucrose, sugar spheres, sulfobutylether beta-cyclodextrin, tragacanth, trehalose, polysorbate 80, xylitol or mixtures thereof.
  • the amount of the fillers is between 65.0% and 80.0% by weight of the total formulation.
  • the filler is microcrystalline cellulose, lactose anhydrous, dicalcium phosphate dihydrate or mixtures thereof.
  • Suitable disintegrants are selected from group comprising croscarmellose sodium, sodium starch glycolate, pregelatinized starch, sodium carboxymethyl cellulose, sodium alginate or mixtures thereof. According to one embodiment of the present invention, preferably the amount of the disintegrants is between 3.0% and 7.0% by weight of the total formulation.
  • the disintegrants is croscarmellose sodium.
  • Suitable binders are selected from the group comprising polyvinylpyrrolidone, carboxymethylcellulose sodium, calcium carbonate, calcium phosphate, calcium sulfate, cellulose, dextrin, polymethacrylates, pregelatinized starch, sodium alginate, synthetic resins, polyethylene glycol, polyvinyl alcohol, starch, pregelatinized starch, sodium alginate, cellulose derivatives such as hydroxypropyl methyl cellulose, hydroxypropyl cellulose, methyl cellulose, polysaccharides, poloxamer, polyacrylamide, aluminium hydroxide, laponit, bentonit, polyoxyethylene-alkyl ether, polydextrose, polyethylene oxide or mixtures thereof.
  • the binder is polyvinylpyrrolidone.
  • Suitable lubricants are selected from the group comprising magnesium stearate, sodium stearyl fumarate, calcium stearate, sodium chlorate, magnesium lauryl sulfate, sodium acetate, sodium benzoate, polyethylene glycol, sodium lauryl sulphate or mixtures thereof.
  • the lubricant is magnesium stearate.
  • the tablet formulation further comprising at least one antioxidant.
  • Suitable antioxidants are selected from the group comprising alpha tocopherol (Vitamin E), quercetine ascorbyl palmitate, ascorbic asit, tartaric asit, cysteine, Lecithin, acetic acid, alpha lipoic acid, butylhydroxyanisole (BHA), butylhydroxytoluene (BHT), erythorbic acid, monothioglycerol, potassium metabisulfite, propyl gallate, sodium ascorbate, sodium metabisulfite, sodium sulfite, citric acid, thymol or mixtures thereof.
  • antioxidants are selected from quercetine, alpha tocopherol(vitamin E), butylhydroxyanisole or butylhydroxytoluene or mixtures thereof.
  • the amount of antioxidants is between 0.1% and 3.0% by weight of the total formulation.
  • particle size distribution means the cumulative volume size distrubition as tested by any conventionally accepted method such as the laser diffraction method (i.e. malvern analysis) .
  • d(0.1) means, the size at which 10% by volume of the particles are finer
  • d(0.5) means the size at which 50% by volume of the particles are finer
  • d (0.9) means the size at which %90 by volume of the particles are finer.
  • vildagliptin has a d (0.1) particle size between 1 pm to 60 pm, preferably 4 pm to 50 pm, between 4 pm to 40 pm, between 4 pm to 30 pm, between 4 pm to 20 pm, between 6 pm to 18 pm.
  • vildagliptin has a d (0.5) particle size between 70 pm to 130 pm, preferably 75 pm to 125 pm, between 80 pm to 120 pm, between 85 pm to 115 pm.
  • vildagliptin has a d (0.9) particle size between 270 pm to 450 pm, preferably 280 pm to 440 pm, between 290 pm to 430 pm, between 300 pm to 420 pm, between 300 pm to 410 pm, between 300 pm to 400 pm.
  • vildagliptin has a d (0.1) particle size between 1 pm to 60 pm, a d (0.5) particle size between 70 pm to 130 pm, a d (0.9) particle size between 270 pm to 450 pm.
  • This invention provides surprisingly better solubility and also helps to ensure desired pharmacotechnical properties.
  • the tablet formulation of the present invention may be prepared, using standard techniques and manufacturing processes well known in the art, such as direct compression, dry granulation, slugging, spray drying.
  • the sachet formulation is obtained by using a dry granulation method therefore, a simple and low-cost production method was employed.
  • Example 1 The tablet formulation comprising vildagliptin
  • Example 2 The tablet formulation comprising vildagliptin
  • a process for example 1 or 2 a) Mixing vildagliptin, colloidal silicone dioxide, a part of lactose anhydrous, a part of microcrystalline cellulose, b) Adding croscarmellose sodium, the remained of lactose anhydrous, the remained of microcrystalline cellulose, polyvinylpyrrolidone and then mixing, c) Compacting the mixture with a compactor and then sieving, d) Adding magnesium stearate and mixing, e) Pressing the mixture to form a tablet.
  • Example 3 The tablet formulation comprising vildagliptin
  • Example 4 The tablet formulation comprising vildagliptin
  • a process for example 3 or 4 a) Mixing vildagliptin, colloidal silicone dioxide, a part of lactose anhydrous, a part of dicalcium phosphate dihydrate and at least one antioxidant, b) Adding croscarmellose sodium, the remained of lactose anhydrous, the remained of dicalcium phosphate dihydrate, polyvinylpyrrolidone and then mixing, c) Compacting the mixture with a compactor and then sieving, d) Adding magnesium stearate and mixing, e) Pressing the mixture to form a tablet.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention relates to a tablet formulation comprising vildagliptin and at least one pharmaceutically acceptable excipient, so the formulation provides the desired stability and pharmacotechnical properties. The present invention also relates to a simple, rapid, cost effective, time-saving and industrially convenient method of preparing the formulation comprising vildagliptin.

Description

A FORMULATION COMPRISING VILDAGLIPTIN AND AT LEAST ONE PHARMACEUTICALLY ACCEPTABLE EXCIPIENT
Field of Invention
The present invention relates to a tablet formulation comprising vildagliptin and at least one pharmaceutically acceptable excipient, so the formulation provides the desired stability and pharmacotechnical properties. The present invention also relates to a simple, rapid, cost effective, time-saving and industrially convenient method of preparing the formulation comprising vildagliptin.
Background of the Invention
Diabetes mellitus is a group of disorders of carbohydrate metabolism in which the action of insulin is diminished or absent through altered secretion, decreased insulin activity or a combination of both factors. There are two main types of diabetes; Type 1 and Type 2:
Type 1 diabetes occurs because the insulin-producing cells of the pancreas (beta cells) are damaged. In Type 1 diabetes, the pancreas makes little or no insulin, so sugar cannot get into the body's cells for use as energy. People with Type 1 diabetes must use insulin injections to control their blood glucose.
In Type 2 diabetes, the pancreas makes insulin, but it either doesn't produce enough, or the insulin does not work properly. This diabetes occurs most often in people who are over 40 years old and overweight. Type 2 diabetes may sometimes be controlled with a combination of diet, weight management, and exercise. However, treatment also may include oral glucose-lowering medications or insulin injections.
Vildagliptin is a dipeptidyl dipeptidase-IV (DPP-IV) inhibitor developed for use in the treatment of type 2 diabetes (non-insulin dependent diabetes). Vildagliptin inhibits the degradation of the dipeptidyl dipeptidase-IV enzyme, thereby inhibiting the effects of incretin hormones, glucagon-like peptide-1 (GLP-1), and of glucose-dependent insulinotropic peptide (GIP). The chemical designation of vildagliptin is (S)-{[(3-hydroxyadamantan-1- yl)amino]acetyl}pyrrolidine-2-carbonitril, with the chemical structure illustrated below in Formula I. Formula I
Vildagliptin is an active agent that is highly-susceptible to air and humidity conditions. When vildagliptin is initially exposed to air and humidity, it degrades structurally and develops chemical behavioral changes. As a result of this, two main problems emerge. The first problem is that the stability of the products developed is not at a desired level and the shelf life thereof is shortened. Secondly, vildagliptin is reactive against the excipients employed in developing formulations. This fact causes impurities and unwanted components to be included into the formulation.
A further problem encountered while developing formulations comprising vildagliptin is flowability. Problems encountered in the flowability of vildagliptin make its production difficult.
The patent application WOOO/34241 discloses vildagliptin or an acid addition salt thereof, as well as their use in diabetes mellitus and obesity.
The patent application W02006/078593 claims a direct-compression formulation of a DPP-IV inhibitor compound, and preferably of vildagliptin or an acid addition salt thereof.
The patent application W02006/135723 discloses a formulation, comprising vildagliptin as an active agent, as well as hydroxypropyl methylcellulose, microcrystalline cellulose, and magnesium stearate.
There is thus still a need for a formulation that is stable against sensitive of vildagliptin and that provides pharmacotechnical properties such as flowability, compressibility and homogeneity.
Detailed Description of the Invention
The main object of the present invention is to provide a formulation comprising vildagliptin having pharmacotechnical properties such as flowability, compressibility and homogeneity. Another object of the present invention is to provide a formulation comprising vildagliptin having desired stability without side reactions and chemical impurities.
According to one embodiment of the invention, a tablet formulation comprises;
10.0-20.0% by weight of vildagliptin,
- 60.0-85.0% by weight of fillers,
1 .0-10.0% by weight of disintegrants,
1 .0-7.0% by weight of binders,
- 0.1 -3.0 % by weight of lubricants,
0.1 -3.0 % by weight of colloidal silicone dioxide in the formulation wherein tablet is free of coating.
In the present invention, colloidal silicone dioxide is used, so while the formulation comprising vildagliptin is provided pharmacotechnical properties, especially, flowability. Also, certain amounts of excipients are used so while the stable formulation is provided without side reactions and chemical impurities. The formulation has been developed by using standard techniques which is a simple and cost-effective method.
According to one embodiment of the present invention, vildagliptin crystal form “Form A” is used in the tablet formulation. The term “vildagliptin” refers to vildagliptin form A in the present invention.
Suitable fillers are selected from group comprising microcrystalline cellulose, lactose anhydrous, dicalcium phosphate dihydrate, ammonium alginate, calcium carbonate, calcium phosphate, calcium sulfate, cellulose, cellulose acetate, dextrates, dextrin, dextrose, erythritol, ethylcellulose, fructose, mannitol, magnesium carbonate, magnesium oxide, maltodextrin, polydextrose, polymethacrylates, sodium alginate, sodium chloride, sorbitol, starch, sucrose, sugar spheres, sulfobutylether beta-cyclodextrin, tragacanth, trehalose, polysorbate 80, xylitol or mixtures thereof.
According to one embodiment of the present invention, preferably the amount of the fillers is between 65.0% and 80.0% by weight of the total formulation.
According to one embodiment of the present invention, the filler is microcrystalline cellulose, lactose anhydrous, dicalcium phosphate dihydrate or mixtures thereof.
Suitable disintegrants are selected from group comprising croscarmellose sodium, sodium starch glycolate, pregelatinized starch, sodium carboxymethyl cellulose, sodium alginate or mixtures thereof. According to one embodiment of the present invention, preferably the amount of the disintegrants is between 3.0% and 7.0% by weight of the total formulation.
According to one embodiment of the present invention, the disintegrants is croscarmellose sodium.
Suitable binders are selected from the group comprising polyvinylpyrrolidone, carboxymethylcellulose sodium, calcium carbonate, calcium phosphate, calcium sulfate, cellulose, dextrin, polymethacrylates, pregelatinized starch, sodium alginate, synthetic resins, polyethylene glycol, polyvinyl alcohol, starch, pregelatinized starch, sodium alginate, cellulose derivatives such as hydroxypropyl methyl cellulose, hydroxypropyl cellulose, methyl cellulose, polysaccharides, poloxamer, polyacrylamide, aluminium hydroxide, laponit, bentonit, polyoxyethylene-alkyl ether, polydextrose, polyethylene oxide or mixtures thereof.
According to one embodiment of the present invention, the binder is polyvinylpyrrolidone.
Suitable lubricants are selected from the group comprising magnesium stearate, sodium stearyl fumarate, calcium stearate, sodium chlorate, magnesium lauryl sulfate, sodium acetate, sodium benzoate, polyethylene glycol, sodium lauryl sulphate or mixtures thereof.
According to this embodiment of the invention, the lubricant is magnesium stearate.
According to one embodiment of the present invention, the tablet formulation further comprising at least one antioxidant.
Suitable antioxidants are selected from the group comprising alpha tocopherol (Vitamin E), quercetine ascorbyl palmitate, ascorbic asit, tartaric asit, cysteine, Lecithin, acetic acid, alpha lipoic acid, butylhydroxyanisole (BHA), butylhydroxytoluene (BHT), erythorbic acid, monothioglycerol, potassium metabisulfite, propyl gallate, sodium ascorbate, sodium metabisulfite, sodium sulfite, citric acid, thymol or mixtures thereof. Preferably, antioxidants are selected from quercetine, alpha tocopherol(vitamin E), butylhydroxyanisole or butylhydroxytoluene or mixtures thereof.
According to this embodiment of the invention, the amount of antioxidants is between 0.1% and 3.0% by weight of the total formulation.
As used here in, ‘particle size distribution’ means the cumulative volume size distrubition as tested by any conventionally accepted method such as the laser diffraction method (i.e. malvern analysis) .The term d(0.1) means, the size at which 10% by volume of the particles are finer and d(0.5) means the size at which 50% by volume of the particles are finer and d (0.9) means the size at which %90 by volume of the particles are finer.
According to this embodiment of the invention, vildagliptin has a d (0.1) particle size between 1 pm to 60 pm, preferably 4 pm to 50 pm, between 4 pm to 40 pm, between 4 pm to 30 pm, between 4 pm to 20 pm, between 6 pm to 18 pm.
According to this embodiment of the invention, vildagliptin has a d (0.5) particle size between 70 pm to 130 pm, preferably 75 pm to 125 pm, between 80 pm to 120 pm, between 85 pm to 115 pm.
According to this embodiment of the invention, vildagliptin has a d (0.9) particle size between 270 pm to 450 pm, preferably 280 pm to 440 pm, between 290 pm to 430 pm, between 300 pm to 420 pm, between 300 pm to 410 pm, between 300 pm to 400 pm.
According to this embodiment of the invention, vildagliptin has a d (0.1) particle size between 1 pm to 60 pm, a d (0.5) particle size between 70 pm to 130 pm, a d (0.9) particle size between 270 pm to 450 pm. This invention provides surprisingly better solubility and also helps to ensure desired pharmacotechnical properties.
The tablet formulation of the present invention may be prepared, using standard techniques and manufacturing processes well known in the art, such as direct compression, dry granulation, slugging, spray drying.
Furthermore, the sachet formulation is obtained by using a dry granulation method therefore, a simple and low-cost production method was employed.
Example 1 : The tablet formulation comprising vildagliptin Example 2: The tablet formulation comprising vildagliptin
A process for example 1 or 2; a) Mixing vildagliptin, colloidal silicone dioxide, a part of lactose anhydrous, a part of microcrystalline cellulose, b) Adding croscarmellose sodium, the remained of lactose anhydrous, the remained of microcrystalline cellulose, polyvinylpyrrolidone and then mixing, c) Compacting the mixture with a compactor and then sieving, d) Adding magnesium stearate and mixing, e) Pressing the mixture to form a tablet.
Example 3: The tablet formulation comprising vildagliptin Example 4: The tablet formulation comprising vildagliptin
A process for example 3 or 4; a) Mixing vildagliptin, colloidal silicone dioxide, a part of lactose anhydrous, a part of dicalcium phosphate dihydrate and at least one antioxidant, b) Adding croscarmellose sodium, the remained of lactose anhydrous, the remained of dicalcium phosphate dihydrate, polyvinylpyrrolidone and then mixing, c) Compacting the mixture with a compactor and then sieving, d) Adding magnesium stearate and mixing, e) Pressing the mixture to form a tablet.

Claims

1 . A tablet formulation comprising
10.0-20.0% by weight of vildagliptin,
- 60.0-85.0% by weight of fillers,
1 .0-10.0% by weight of disintegrants,
1 .0-7.0% by weight of binders,
- 0.1 -3.0 % by weight of lubricants,
0.1 -3.0 % by weight of colloidal silicone dioxide in the formulation wherein tablet is free of coating.
2. The tablet formulation according to claim 1 , wherein vildagliptin crystal form “form A” is used in the formulation.
3. The tablet formulation according to claim 1 , wherein fillers are selected from group comprising microcrystalline cellulose, lactose anhydrous, dicalcium phosphate dihydrate, ammonium alginate, calcium carbonate, calcium phosphate, calcium sulfate, cellulose, cellulose acetate, dextrates, dextrin, dextrose, erythritol, ethylcellulose, fructose, mannitol, magnesium carbonate, magnesium oxide, maltodextrin, polydextrose, polymethacrylates, sodium alginate, sodium chloride, sorbitol, starch, sucrose, sugar spheres, sulfobutylether beta-cyclodextrin, tragacanth, trehalose, polysorbate 80, xylitol or mixtures thereof.
4. The tablet formulation according to claim 1 , wherein disintegrants are selected from group comprising croscarmellose sodium, sodium starch glycolate, pregelatinized starch, sodium carboxymethyl cellulose, sodium alginate or mixtures thereof.
5. The tablet formulation according to claim 1 , wherein binders are selected from the group comprising polyvinylpyrrolidone, carboxymethylcellulose sodium, calcium carbonate, calcium phosphate, calcium sulfate, cellulose, dextrin, polymethacrylates, pregelatinized starch, sodium alginate, synthetic resins, polyethylene glycol, polyvinyl alcohol, starch, pregelatinized starch, sodium alginate, cellulose derivatives such as hydroxypropyl methyl cellulose, hydroxypropyl cellulose, methyl cellulose, polysaccharides, poloxamer, polyacrylamide, aluminium hydroxide, laponit, bentonit, polyoxyethylene-alkyl ether, polydextrose, polyethylene oxide or mixtures thereof.
6. The tablet formulation according to claim 1 , wherein lubricants are selected from the group comprising magnesium stearate, sodium stearyl fumarate, calcium stearate, sodium chlorate, magnesium lauryl sulfate, sodium acetate, sodium benzoate, polyethylene glycol, sodium lauryl sulphate or mixtures thereof.
7. The tablet formulation according to claim 1 , further comprising at least one antioxidant.
8. The tablet formulation according to claim 7, wherein antioxidants are selected from the group comprising alpha tocopherol (Vitamin E), quercetine ascorbyl palmitate, ascorbic asit, tartaric asit, cysteine, Lecithin, acetic acid, alpha lipoic acid, butylhydroxyanisole (BHA), butylhydroxytoluene (BHT), erythorbic acid, monothioglycerol, potassium metabisulfite, propyl gallate, sodium ascorbate, sodium metabisulfite, sodium sulfite, citric acid, thymol or mixtures thereof. Preferably, antioxidants are selected from quercetine, alpha tocopherol(vitamin E), butylhydroxyanisole or butylhydroxytoluene or mixtures thereof.
9. The tablet formulation according to claim 1 , wherein vildagliptin has a d (0.1) particle size between 1 pm to 60 pm, a d (0.5) particle size between 70 pm to 130 pm, a d (0.9) particle size between 270 pm to 450 pm,
10. The tablet formulation according to claim 1 , comprising vildagliptin, microcrystalline cellulose, croscarmellose sodium, lactose anhydrous, polyvinylpyrrolidone, colloidal silicone dioxide, magnesium stearate.
11. The tablet formulation according to claim 1 , comprising vildagliptin, dicalcium phosphate dihydrate, croscarmellose sodium, lactose anhydrous, at least one antioxidant, polyvinylpyrrolidone, colloidal silicone dioxide, magnesium stearate.
EP21837553.3A 2020-07-06 2021-05-07 FORMULATION COMPRISING VILDAGLIPTIN AND AT LEAST ONE PHARMACEUTICALLY ACCEPTABLE EXCIPIENT Pending EP4175632A4 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR2020/10700A TR202010700A2 (en) 2020-07-06 2020-07-06 A FORMULATION CONTAINING VILDAGLIPTIN AND AT LEAST ONE PHARMACEUTICALLY ACCEPTABLE EXCLUSIVE
PCT/TR2021/050444 WO2022010436A1 (en) 2020-07-06 2021-05-07 A formulation comprising vildagliptin and at least one pharmaceutically acceptable excipient

Publications (2)

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EP4175632A1 true EP4175632A1 (en) 2023-05-10
EP4175632A4 EP4175632A4 (en) 2024-08-07

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Country Link
EP (1) EP4175632A4 (en)
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CN101106977A (en) * 2005-01-18 2008-01-16 诺瓦提斯公司 Formulation and method of direct compression tablet
GT200600008A (en) * 2005-01-18 2006-08-09 FORMULATION OF DIRECT COMPRESSION AND PROCESS
GT200600218A (en) * 2005-06-10 2007-03-28 FORMULATION AND PROCESS OF DIRECT COMPRESSION
EP2915528A1 (en) * 2014-03-06 2015-09-09 Sanovel Ilac Sanayi ve Ticaret A.S. Vildagliptin formulation process under inert gas atmosphere
WO2019219920A1 (en) * 2018-05-18 2019-11-21 Galenicum Health S.L.U Stable pharmaceutical compositions of dpp-iv inhibitors in combination with metformin in the form of immediate release tablets

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