EP4125824A1 - A sachet formulation comprising metformin and dapagliflozin - Google Patents

A sachet formulation comprising metformin and dapagliflozin

Info

Publication number
EP4125824A1
EP4125824A1 EP21776477.8A EP21776477A EP4125824A1 EP 4125824 A1 EP4125824 A1 EP 4125824A1 EP 21776477 A EP21776477 A EP 21776477A EP 4125824 A1 EP4125824 A1 EP 4125824A1
Authority
EP
European Patent Office
Prior art keywords
weight
metformin
sodium
sachet
dapagliflozin
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
EP21776477.8A
Other languages
German (de)
French (fr)
Other versions
EP4125824A4 (en
Inventor
Abdullah TASKIN
Muge ULUSOY BOZYEL
Yavuz Dedeoglu
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 EP4125824A1 publication Critical patent/EP4125824A1/en
Publication of EP4125824A4 publication Critical patent/EP4125824A4/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
    • A61K9/0087—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
    • 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
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • 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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof

Definitions

  • the present invention relates to a sachet formulation comprising metformin, dapagliflozin and at least one pharmaceutically acceptable excipient.
  • 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.
  • Dapagliflozin is a sodium-glucose cotransporter 2 inhibitor (SGLT2) indicated in the treatment of diabetes mellitus, in particular type 2 diabetes. It prevents reabsorption of at least 90% of the glucose in the kidney and facilitates elimination of the glucose through the urine.
  • SGLT2 sodium-glucose cotransporter 2 inhibitor
  • Dapagliflozin also known as (1 S)-1 ,5-Anhydro-1 -C-[4-chloro-3-[(4-ethoxyphenyl)methyl] phenyl]-D-glucitol, is represented by the structure of Formula I.
  • Metformin is antidiabetics having an orally-administrated biguanide structure. Oral doses of metformin are generally recommended in the range of 500 to 2500 mg a day and a single dose may vary from 250 to 1000 mg. It is used singly or in combination with sulfonylureas, alpha-glucosidase inhibitors, or insulin.
  • metformin is 1 ,1 -dimethyl biguanide, has the following chemical structure of Formula II.
  • metformin Although metformin is effective at lowering blood glucose levels, its use is associated with gastrointestinal (Gl) adverse effects, particularly diarrhea and nausea. These adverse effects may limit the tolerated dose of metformin and cause patients to discontinue the therapy.
  • Gl gastrointestinal
  • IN2012DN4094A application discloses an immediate release pharmaceutical formulation which includes a tablet or capsule formulation comprising metformin and the dapagliflozin or its propylene glycol hydrate.
  • CN109528706A application discloses a medicine composition for treatment of diabetes, which includes dapagliflozin and metformin hydrochloride according to mass ratio of 1 :50 to 1 :200.
  • a medicine composition for treatment of diabetes which includes dapagliflozin and metformin hydrochloride according to mass ratio of 1 :50 to 1 :200.
  • the method by control the amount of both the metformin hydrochloride amount and the dapagliflozin, mixing uniformity of the two active components is guaranteed, and flowability and tabletability of the particles are ensured.
  • Tablet and capsule forms comprising metformin and dapagliflozin are known in the prior art. But, the compressibility of metformin is poor, and how to obtain a tablet or a capsule having an acceptable mechanical strength is an important problem in formulation development.
  • the formulation is present in the form of a sachet, also the formulation provides desired dissolution profile.
  • the formulation has been developed by using standard techniques which is simple and cost-effective method.
  • the main object of the present invention is to provide a sachet formulation comprising metformin, dapagliflozin and at least one pharmaceutically acceptable excipient.
  • Another object of the present invention is to provide pharmacotechnical properties such as flowability and homogeneity and the desired dissolution profile.
  • Another object of the present invention is to provide a sachet formulation comprising metformin and dapagliflozin for increasing patient compliance.
  • metalformin refers to not only metformin, but also its other pharmaceutically acceptable salt, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs or pharmaceutically acceptable prodrugs thereof.
  • metformin can present in the invention as metformin free base or metformin hydrochloride.
  • dapagliflozin refers to not only dapagliflozin, but also its other pharmaceutically acceptable salt, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs or pharmaceutically acceptable prodrugs thereof.
  • sachet formulations have become an issue with increasing importance in terms of patient compliance as compared to conventional solid dosage forms such as capsules and tablets. This issue is more important in terms of patients having difficulty in swallowing.
  • sachet formulations are one of the advantageous routes for administering the drugs comprising metformin and dapagliflozin and provide a higher patient compliance along with recommended pharmaceutical therapies.
  • the term “sachet” will refer to an envelope or bag for a granulate, while “granulate” refers to particles, granulate or spheronised particles.
  • the sachets require no special shaping or molding operations. Thus, the compaction, compression or tamping steps used with other dosage forms are not needed.
  • a sachet formulation comprises metformin, dapagliflozin and at least one pharmaceutically acceptable excipient.
  • the amount of metformin is 10.0% to 20.0% by weight of the total formulation.
  • the amount of dapagliflozin is 0.05% to 5.0% or 0.05% to 2.0% or 0.05% to 1.0% by weight of the total formulation.
  • At least one pharmaceutically acceptable excipient is selected from the group comprising fillers, pH adjusters, flavouring agent, aromas or mixtures.
  • Suitable fillers are selected from the group comprising mannitol, microcrystalline cellulose, sorbitol, sucrose, inorganic salts, calcium salts, spray-dried lactose, calcium silicate, polysaccharides, dextrose, sodium chloride, dextrates, lactitol, sugar pellet, lactose monohydrate, starch, maltodextrin, dibasic calcium phosphate, sucrose-maltodextrin mixtures, xylitol, trehalose, heavy magnesium carbonate, isomalt or mixtures thereof.
  • the amount of the fillers is 5.0% to 60.0% by weight of the total formulation.
  • the amount of the fillers is 8.0% to 50.0% or 10.0% to 40.0% or 12.0% to 35.0% by weight of the total formulation.
  • the filler is mannitol.
  • Suitable pH adjusters are selected from the group comprising citric acid, sodium bicarbonate, aluminum potassium sulfate, anhydrous disodium hydrogen phosphate, potassium carbonate, anhydrous sodium dihydrogen phosphate, dibasic potassium sulfate, calcium carbonate, nicotinic acid, dilute hydrochloric acid, glacial acetic acid, lactic acid, maleic acid, monobasic potassium phosphate, phosphoric acid, adipic acid, sodium acetate, sodium carbonate, sodium citrate, sodium dihydrogen phosphate dihydrate, tartaric acid, tribasic sodium phosphate or mixtures thereof.
  • the amount of the pH adjusters is 4.0% to 80.0% by weight of the total formulation.
  • the amount of the pH adjusters is 5.0% to 70.0% or 5.0% to 60.0% or 5.0% to 50.0% or 5.0% to 40.0% or 5.0% to 30.0% or 5.0% to 20.0% or 5.0% to 10.0% by weight of the total formulation.
  • the pH adjuster is citric acid or sodium bicarbonate or mixtures thereof.
  • Suitable flavourings are selected from the group comprising sucralose, sugar alcohols, sugars, liquid glucose, sucrose, saccharine sodium, xylitol, sorbitol, erythritol or mixtures thereof.
  • the amount of the flavourings is 0.1% to 10.0% by weight of the total formulation.
  • the amount of the flavourings is 0.1% to 5.0% or 1 .0% to 3.0% by weight of the total formulation.
  • the flavouring is sucralose.
  • Suitable aromas are selected from the group comprising menthol, peppermint, cinnamon, chocolate, vanillin, fruit essences, cherry, orange, strawberry, grape, black currant, raspberry, banana, red fruits, wild berries, cardamom, anise, ethyl vanillin or mixtures thereof.
  • the amount of the aromas is 0.1% to 10.0% by weight of the total formulation.
  • the amount of the aromas is 0.1% to 5.0% or 1.0% to 3.0% by weight of the total formulation.
  • flavourings or aromas are used in the formulation, it is observed that the use of the formulation for the patient is very easy.
  • the pharmaceutical composition of the present invention may be prepared, using standard techniques and manufacturing processes well known in the art, such as direct compression, wet or dry granulation, hot melt granulation, hot melt extrusion, fluidized bed granulation, extrusion/spheronization, slugging, spray drying and solvent evaporation.
  • the sachet formulation is obtained by using a wet granulation method therefore, a simple and low-cost production method was employed.
  • the sachet formulation can be used for treatment on the diabetes type II.
  • Example 1 The sachet formulation comprising metformin and dapagliflozin
  • the sachet content is adjusted so that the sachet weight is 4-5 grams.
  • Process for example 1 The process for the preparation of the sachet formulation comprises the following steps: a) Granulating dapagliflozin, metformin and at least one filler with alcohol or alcohol/water, b) Then, drying and sieving, c) Then, adding pH adjusters, at least one flavouring and aromas and mixing, d) Filling the mixture into sachets under low humidity conditions.
  • Example 2 The sachet formulation comprising metformin and dapagliflozin
  • the sachet content is adjusted so that the sachet weight is 4-5 grams.
  • Process for example 2 The process for the preparation of the sachet formulation comprises the following steps: a) Granulating dapagliflozin, metformin and mannitol with alcohol or alcohol/water, b) Then, drying and sieving, c) Then, adding sodium bicarbonate, citric acid, sucralose, aroma and mixing, d) Filling the mixture into sachets under low humidity conditions.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Diabetes (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Biophysics (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)

Abstract

The present invention relates to a sachet formulation comprising metformin, dapagliflozin and at least one pharmaceutically acceptable excipient.

Description

A SACHET FORMULATION COMPRISING METFORMIN AND DAPAGLIFLOZIN
Field of the Invention
The present invention relates to a sachet formulation comprising metformin, dapagliflozin and at least one pharmaceutically acceptable excipient.
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.
Dapagliflozin is a sodium-glucose cotransporter 2 inhibitor (SGLT2) indicated in the treatment of diabetes mellitus, in particular type 2 diabetes. It prevents reabsorption of at least 90% of the glucose in the kidney and facilitates elimination of the glucose through the urine.
Dapagliflozin, also known as (1 S)-1 ,5-Anhydro-1 -C-[4-chloro-3-[(4-ethoxyphenyl)methyl] phenyl]-D-glucitol, is represented by the structure of Formula I.
Formula I
Metformin is antidiabetics having an orally-administrated biguanide structure. Oral doses of metformin are generally recommended in the range of 500 to 2500 mg a day and a single dose may vary from 250 to 1000 mg. It is used singly or in combination with sulfonylureas, alpha-glucosidase inhibitors, or insulin.
The chemical name of metformin is 1 ,1 -dimethyl biguanide, has the following chemical structure of Formula II.
Formula II
Although metformin is effective at lowering blood glucose levels, its use is associated with gastrointestinal (Gl) adverse effects, particularly diarrhea and nausea. These adverse effects may limit the tolerated dose of metformin and cause patients to discontinue the therapy.
IN2012DN4094A application discloses an immediate release pharmaceutical formulation which includes a tablet or capsule formulation comprising metformin and the dapagliflozin or its propylene glycol hydrate.
CN109528706A application discloses a medicine composition for treatment of diabetes, which includes dapagliflozin and metformin hydrochloride according to mass ratio of 1 :50 to 1 :200. In the method, by control the amount of both the metformin hydrochloride amount and the dapagliflozin, mixing uniformity of the two active components is guaranteed, and flowability and tabletability of the particles are ensured.
Tablet and capsule forms comprising metformin and dapagliflozin are known in the prior art. But, the compressibility of metformin is poor, and how to obtain a tablet or a capsule having an acceptable mechanical strength is an important problem in formulation development.
There is thus still a need for a formulation comprising metformin and dapagliflozin that provides pharmacotechnical properties such as flowability, compressibility and homogeneity. In the present invention, the formulation is present in the form of a sachet, also the formulation provides desired dissolution profile. The formulation has been developed by using standard techniques which is simple and cost-effective method. Detailed Description of the Invention
The main object of the present invention is to provide a sachet formulation comprising metformin, dapagliflozin and at least one pharmaceutically acceptable excipient.
Another object of the present invention is to provide pharmacotechnical properties such as flowability and homogeneity and the desired dissolution profile.
Another object of the present invention is to provide a sachet formulation comprising metformin and dapagliflozin for increasing patient compliance.
The term "metformin" as used throughout the specification refers to not only metformin, but also its other pharmaceutically acceptable salt, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs or pharmaceutically acceptable prodrugs thereof.
The metformin can present in the invention as metformin free base or metformin hydrochloride.
The term "dapagliflozin" as used throughout the specification refers to not only dapagliflozin, but also its other pharmaceutically acceptable salt, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs or pharmaceutically acceptable prodrugs thereof.
In terms of physical properties, the compressibility of metformin is poor, and how to obtain a tablet or a capsule having an acceptable mechanical strength is an important problem in formulation development.
It has been surprisingly found that using a sachet formulation comprising metformin and dapagliflozin ensures the desired dissolution profile and high physically and chemically stability provides. The sachet formulations with a good solubility result in a homogenous mixture.
Also, concerning oral administration, sachet formulations have become an issue with increasing importance in terms of patient compliance as compared to conventional solid dosage forms such as capsules and tablets. This issue is more important in terms of patients having difficulty in swallowing. For these reasons, sachet formulations are one of the advantageous routes for administering the drugs comprising metformin and dapagliflozin and provide a higher patient compliance along with recommended pharmaceutical therapies. The term “sachet” will refer to an envelope or bag for a granulate, while “granulate” refers to particles, granulate or spheronised particles. The sachets require no special shaping or molding operations. Thus, the compaction, compression or tamping steps used with other dosage forms are not needed.
According to one embodiment of the invention, a sachet formulation comprises metformin, dapagliflozin and at least one pharmaceutically acceptable excipient.
According to one embodiment of the invention, the amount of metformin is 10.0% to 20.0% by weight of the total formulation.
According to one embodiment of the invention, the amount of dapagliflozin is 0.05% to 5.0% or 0.05% to 2.0% or 0.05% to 1.0% by weight of the total formulation.
According to one embodiment of the invention, at least one pharmaceutically acceptable excipient is selected from the group comprising fillers, pH adjusters, flavouring agent, aromas or mixtures.
Suitable fillers are selected from the group comprising mannitol, microcrystalline cellulose, sorbitol, sucrose, inorganic salts, calcium salts, spray-dried lactose, calcium silicate, polysaccharides, dextrose, sodium chloride, dextrates, lactitol, sugar pellet, lactose monohydrate, starch, maltodextrin, dibasic calcium phosphate, sucrose-maltodextrin mixtures, xylitol, trehalose, heavy magnesium carbonate, isomalt or mixtures thereof.
According to one embodiment of the invention, the amount of the fillers is 5.0% to 60.0% by weight of the total formulation. The amount of the fillers is 8.0% to 50.0% or 10.0% to 40.0% or 12.0% to 35.0% by weight of the total formulation.
According to one embodiment of the invention, the filler is mannitol.
Suitable pH adjusters are selected from the group comprising citric acid, sodium bicarbonate, aluminum potassium sulfate, anhydrous disodium hydrogen phosphate, potassium carbonate, anhydrous sodium dihydrogen phosphate, dibasic potassium sulfate, calcium carbonate, nicotinic acid, dilute hydrochloric acid, glacial acetic acid, lactic acid, maleic acid, monobasic potassium phosphate, phosphoric acid, adipic acid, sodium acetate, sodium carbonate, sodium citrate, sodium dihydrogen phosphate dihydrate, tartaric acid, tribasic sodium phosphate or mixtures thereof.
According to one embodiment of the invention, the amount of the pH adjusters is 4.0% to 80.0% by weight of the total formulation. The amount of the pH adjusters is 5.0% to 70.0% or 5.0% to 60.0% or 5.0% to 50.0% or 5.0% to 40.0% or 5.0% to 30.0% or 5.0% to 20.0% or 5.0% to 10.0% by weight of the total formulation.
According to one embodiment of the invention, the pH adjuster is citric acid or sodium bicarbonate or mixtures thereof.
Suitable flavourings are selected from the group comprising sucralose, sugar alcohols, sugars, liquid glucose, sucrose, saccharine sodium, xylitol, sorbitol, erythritol or mixtures thereof.
According to one embodiment of the invention, the amount of the flavourings is 0.1% to 10.0% by weight of the total formulation. The amount of the flavourings is 0.1% to 5.0% or 1 .0% to 3.0% by weight of the total formulation.
According to one embodiment of the invention, the flavouring is sucralose.
Suitable aromas are selected from the group comprising menthol, peppermint, cinnamon, chocolate, vanillin, fruit essences, cherry, orange, strawberry, grape, black currant, raspberry, banana, red fruits, wild berries, cardamom, anise, ethyl vanillin or mixtures thereof.
According to one embodiment of the invention, the amount of the aromas is 0.1% to 10.0% by weight of the total formulation. The amount of the aromas is 0.1% to 5.0% or 1.0% to 3.0% by weight of the total formulation.
When flavourings or aromas are used in the formulation, it is observed that the use of the formulation for the patient is very easy.
The pharmaceutical composition of the present invention may be prepared, using standard techniques and manufacturing processes well known in the art, such as direct compression, wet or dry granulation, hot melt granulation, hot melt extrusion, fluidized bed granulation, extrusion/spheronization, slugging, spray drying and solvent evaporation.
Furthermore, the sachet formulation is obtained by using a wet granulation method therefore, a simple and low-cost production method was employed.
The sachet formulation can be used for treatment on the diabetes type II. Example 1 : The sachet formulation comprising metformin and dapagliflozin
The sachet content is adjusted so that the sachet weight is 4-5 grams.
Process for example 1 : The process for the preparation of the sachet formulation comprises the following steps: a) Granulating dapagliflozin, metformin and at least one filler with alcohol or alcohol/water, b) Then, drying and sieving, c) Then, adding pH adjusters, at least one flavouring and aromas and mixing, d) Filling the mixture into sachets under low humidity conditions.
Example 2: The sachet formulation comprising metformin and dapagliflozin
The sachet content is adjusted so that the sachet weight is 4-5 grams.
Process for example 2: The process for the preparation of the sachet formulation comprises the following steps: a) Granulating dapagliflozin, metformin and mannitol with alcohol or alcohol/water, b) Then, drying and sieving, c) Then, adding sodium bicarbonate, citric acid, sucralose, aroma and mixing, d) Filling the mixture into sachets under low humidity conditions.

Claims

1. A sachet formulation comprising metformin, dapagliflozin and at least one pharmaceutically acceptable excipient.
2. The sachet formulation according to claim 1 , wherein the amount of metformin is 10.0% to 20.0% by weight of the total formulation.
3. The sachet formulation according to claim 1 , wherein the amount of dapagliflozin is 0.05% to 5.0% by weight of the total formulation.
4. The sachet formulation according to claim 1 , wherein at least one pharmaceutically acceptable excipient is selected from the group comprising fillers, pH adjusters, flavouring agent, aromas or mixtures thereof.
5. The sachet formulation according to claim 4, wherein fillers are selected from the group comprising mannitol, microcrystalline cellulose, sorbitol, sucrose, inorganic salts, calcium salts, spray-dried lactose, calcium silicate, polysaccharides, dextrose, sodium chloride, dextrates, lactitol, sugar pellet, lactose monohydrate, starch, maltodextrin, dibasic calcium phosphate, sucrose-maltodextrin mixtures, xylitol, trehalose, heavy magnesium carbonate, isomalt or mixtures thereof.
6. The sachet formulation according to claim 4, wherein pH adjusters are selected from the group comprising citric acid, sodium bicarbonate, aluminum potassium sulfate, anhydrous disodium hydrogen phosphate, potassium carbonate, anhydrous sodium dihydrogen phosphate, dibasic potassium sulfate, calcium carbonate, nicotinic acid, dilute hydrochloric acid, glacial acetic acid, lactic acid, maleic acid, monobasic potassium phosphate, phosphoric acid, adipic acid, sodium acetate, sodium carbonate, sodium citrate, sodium dihydrogen phosphate dihydrate, tartaric acid, tribasic sodium phosphate or mixtures thereof.
7. The sachet formulation according to claim 4, wherein flavourings are selected from the group comprising sucralose, sugar alcohols, sugars, liquid glucose, sucrose, saccharine sodium, xylitol, sorbitol, erythritol or mixtures thereof.
8. The sachet formulation according to claim 4, wherein aromas are selected from the group comprising menthol, peppermint, cinnamon, chocolate, vanillin, fruit essences, cherry, orange, strawberry, grape, black currant, raspberry, banana, red fruits, wild berries, cardamom, anise, ethyl vanillin or mixtures thereof.
9. The sachet formulation according to any preceding claim, comprising;
0.05 - 0.2% by weight of dapagliflozin,
10.0 - 20.0% by weight of metformin,
5.0 - 60.0% by weight of mannitol,
2.0 - 40.0% by weight of sodium bicarbonate,
2.0 - 40.0% by weight of citric acid,
0.1 - 10.0% by weight of sucralose,
0.1 - 10.0% by weight of aroma of the total formulation.
10. A process for preparing the sachet formulation according to claim 9, comprising the following steps; a) Granulating dapagliflozin, metformin and mannitol with alcohol or alcohol/water, b) Then, drying and sieving, c) Then, adding sodium bicarbonate, citric acid, sucralose, aroma and mixing, d) Filling the mixture into sachets under low humidity conditions.
EP21776477.8A 2020-03-27 2021-01-15 A sachet formulation comprising metformin and dapagliflozin Pending EP4125824A4 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR2020/04809A TR202004809A2 (en) 2020-03-27 2020-03-27 A sachet formulation comprising metformin and dapagliflozin
PCT/TR2021/050029 WO2021194446A1 (en) 2020-03-27 2021-01-15 A sachet formulation comprising metformin and dapagliflozin

Publications (2)

Publication Number Publication Date
EP4125824A1 true EP4125824A1 (en) 2023-02-08
EP4125824A4 EP4125824A4 (en) 2023-12-27

Family

ID=77892783

Family Applications (1)

Application Number Title Priority Date Filing Date
EP21776477.8A Pending EP4125824A4 (en) 2020-03-27 2021-01-15 A sachet formulation comprising metformin and dapagliflozin

Country Status (3)

Country Link
EP (1) EP4125824A4 (en)
TR (1) TR202004809A2 (en)
WO (1) WO2021194446A1 (en)

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10360924A1 (en) * 2003-12-23 2005-07-28 IIP - Institut für industrielle Pharmazie, Forschungs- und Entwicklungsgesellschaft mbH Composition containing metformin, useful as antidiabetic, is formulated as water-soluble granules for administration, after dissolution, through a gastric tube
PL2498759T3 (en) * 2009-11-13 2019-03-29 Astrazeneca Ab Immediate release tablet formulations
WO2013077825A1 (en) * 2011-11-23 2013-05-30 Mahmut Bilgic Preparation process for a formulation comprising metformin
WO2013077822A1 (en) * 2011-11-23 2013-05-30 Mahmut Bilgic New formulations for treatment of diabetes
CN103462900A (en) * 2013-09-02 2013-12-25 天津市聚星康华医药科技有限公司 Metformin hydrochloride dry suspension and preparation method thereof
US20190110994A1 (en) * 2016-03-31 2019-04-18 Lupin Limited Pharmaceutical composition of dapagliflozin

Also Published As

Publication number Publication date
TR202004809A2 (en) 2021-10-21
WO2021194446A1 (en) 2021-09-30
EP4125824A4 (en) 2023-12-27

Similar Documents

Publication Publication Date Title
JP7216055B2 (en) Pharmaceutical composition
US20200323776A1 (en) Diclofenac formulations and methods of use
WO2021240531A1 (en) Transmucosal dosage forms of remdesivir
EP2661252A1 (en) Water soluble dosage forms
EP2377522B1 (en) Orally disintegrating tablet formulations of mirtazapine and process for preparing the same
EP3122330B1 (en) Pharmaceutical compositions comprising levocetirizine
US11020349B1 (en) Transmucosal dosage forms of remdesivir
US20150072014A1 (en) Pharmaceutical Compositions of Sodium Picosulfate, Magnesium Oxide and Citric Acid
US9717692B2 (en) Effervescent formulations comprising dexketoprofen
EP4125824A1 (en) A sachet formulation comprising metformin and dapagliflozin
WO2021054912A1 (en) Effervescent tablet formulations comprising dapagliflozin and metformin
KR101352689B1 (en) Microgranule preparations comprising agglumerate units consisting of discontinuous phase and continuous phase
KR20100008419A (en) Stability increased fast soluble amlodipine tablet and processes for the preparation thereof
JPH11116465A (en) Rapidly dissolvable preparation and its production
KR102259798B1 (en) Oral tablet formulation of lenalidomide with improved disintegration
KR102339817B1 (en) An oral solid formulation containing oseltamivir and a process for the preparation thereof
WO2022153334A1 (en) Transmucosal dosage forms of foscarnet
WO2024047352A1 (en) An orodispersible pharmaceutical composition of fexofenadine and its process of preparation.
WO2022155507A1 (en) Transmucosal dosage forms of brexanolone
EP4008315A1 (en) A process for formulations of dapagliflozin and metformin hydrochloride
US20240091367A1 (en) Orally disintegrating palatable formulations of drotaverine and method of preparation thereof
GB2619970A (en) An orodispersible pharmaceutical composition of baclofen and its process of preparation
KR20130025851A (en) Tablet quickly disintegrating containg megestrol and method for producing the same
PL237530B1 (en) Analgesic and anti-inflammatory pharmaceutical composition for use in the prevention of fever and/or pain, in particular for use in mouth and throat inflammation

Legal Events

Date Code Title Description
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE

PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE

17P Request for examination filed

Effective date: 20220927

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

DAV Request for validation of the european patent (deleted)
DAX Request for extension of the european patent (deleted)
P01 Opt-out of the competence of the unified patent court (upc) registered

Effective date: 20230708

A4 Supplementary search report drawn up and despatched

Effective date: 20231127

RIC1 Information provided on ipc code assigned before grant

Ipc: A61K 47/12 20060101ALI20231121BHEP

Ipc: A61K 47/02 20060101ALI20231121BHEP

Ipc: A61K 31/70 20060101ALI20231121BHEP

Ipc: A61K 9/16 20060101ALI20231121BHEP

Ipc: A61K 9/00 20060101ALI20231121BHEP

Ipc: A61P 3/10 20060101ALI20231121BHEP

Ipc: A61K 31/351 20060101ALI20231121BHEP

Ipc: A61K 31/155 20060101ALI20231121BHEP

Ipc: A61K 9/20 20060101AFI20231121BHEP