WO2020240594A1 - Composition pharmaceutique pour le traitement du diabète sucré - Google Patents

Composition pharmaceutique pour le traitement du diabète sucré Download PDF

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Publication number
WO2020240594A1
WO2020240594A1 PCT/IN2020/050480 IN2020050480W WO2020240594A1 WO 2020240594 A1 WO2020240594 A1 WO 2020240594A1 IN 2020050480 W IN2020050480 W IN 2020050480W WO 2020240594 A1 WO2020240594 A1 WO 2020240594A1
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composition
ranging
viscosity
cps
cellulose
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PCT/IN2020/050480
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English (en)
Inventor
Vijaykumar PATIL
Manisha PATIL
Rajan Verma
Raviraj PILLAI
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Abbott Healthcare Pvt. Ltd.
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Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=71738258&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO2020240594(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Abbott Healthcare Pvt. Ltd. filed Critical Abbott Healthcare Pvt. Ltd.
Priority to MX2021014541A priority Critical patent/MX2021014541A/es
Priority to BR112021024099A priority patent/BR112021024099A2/pt
Priority to CR20220001A priority patent/CR20220001A/es
Priority to PE2021001978A priority patent/PE20220644A1/es
Publication of WO2020240594A1 publication Critical patent/WO2020240594A1/fr
Priority to CONC2021/0018031A priority patent/CO2021018031A2/es

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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
    • A61K9/20—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
    • 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
    • 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
    • A61K31/403—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 condensed with carbocyclic rings, e.g. carbazole
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A61K31/4162—1,2-Diazoles condensed with heterocyclic ring systems
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • 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
    • A61K31/69—Boron compounds

Definitions

  • the present invention relates to a pharmaceutical composition of Dipeptidyl peptidase- IV (DPP-IV) inhibitors for use in treatment of Diabetes Mellitus (DM). More particularly, the invention relates to a modified release dosage form comprising a composition of Vildagliptin or a pharmaceutically acceptable salt thereof with desired physical and chemical parameters.
  • DPP-IV Dipeptidyl peptidase- IV
  • the invention also provides various formulations and methods of preparing the same.
  • Diabetes mellitus type 2 (also known as type 2 diabetes) is a long-term metabolic disorder that is characterized by high blood sugar, insulin resistance, and relative lack of insulin.
  • type 2 diabetes is a long-term metabolic disorder that is characterized by high blood sugar, insulin resistance, and relative lack of insulin.
  • the development of type 2 diabetes is caused by a combination of lifestyle and genetic factors. While some of these factors are under personal control, such as diet and obesity, other factors are not, such as increasing age, female gender, and genetics. It is estimated that 366 million people had type 2 diabetes mellitus in 2011; by 2030 this would have risen to 552 million. Thus, research for anti-diabetic drugs becomes important as type 2 diabetes is an incredibly prevalent disease in the modern world and new treatment choices are much needed.
  • DPP-IV Dipeptidyl peptidase- IV
  • a compound having a DPP-IV inhibitory activity is expected to show effect on impaired glucose tolerance, postprandial hyperglycemia and fasting hyperglycemia observed in type I and type II diabetes and the like, obesity or diabetic complications associated therewith and the like.
  • Vildagliptin is an oral anti-hyperglycemic agent (anti-diabetic drug) of the dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs.
  • Dipeptidyl peptidase-4 (DPP-4) is the enzyme responsible for the rapid degradation of the incretin hormones glucagon-like peptide- 1 (GLP-1)
  • g 1 uco se-dependent insulinotropic peptide GIP
  • This activity increases levels of active incretins and enhances pancreatic islet a- and b-cell responsiveness to glucose, thus improving insulin secretion and reducing inappropriate glucagon production, improving insulin sensitivity, improving postprandial lipid and lipoprotein metabolism, and reducing fasting and prandial glucose and Fib Ale.
  • Vildagliptin has been shown to reduce hyperglycemia (high blood sugar).
  • Non-adherence is a serious problem in patients on long-term treatment, accounting for up to 50% of cases where drugs fall short of their therapeutic goals.
  • the benefits of extended duration of treatment may not be sufficiently apparent.
  • Adherence problems are prevalent where self-administration of treatment is required, including acute and chronic illnesses, a prominent disease being diabetes. And once daily dosing might be of great importance in resource-limited settings.
  • An extended release dosage form allows a drug to be slowly released in the body over an extended period of time especially to reduce dosing frequency.
  • these formulations typically keep the therapeutic dose at a steady level in the body for longer periods of time. Though they typically have a slightly slower onset compared to their immediate-release counterparts, however, they maintain a more consistent level of the drug in the body, Hence, better treatment outcomes for longer periods of time while also lowering the occurrence of side effects with improved patient compliance can be achieved with an extended release dosage form of Vildagliptin.
  • compressed tablets are the most widely used solid dosage form so they must satisfy a number of physical requirements in terms of hardness, disintegration ability, friability and uniformity.
  • direct compression can be utilized. Direct compression is a popular choice because it provides the shortest, most effective, least complex way to produce tablets. Further, moisture or heat sensitive ingredients can also be used in this type of process.
  • One of the principal risk factors for segregation is the wide particle size distribution in direct compression formulations, in which active ingredients tend to be at the fine end of the range. Where there is a wide range of particle sizes, there is an increased likelihood of sifting, where the smaller particles 'slip through' the bigger ones.
  • Other bulk powder properties are also important for successful tableting, such as good flowability, and all of these factors combine to place a high requirement on the excipients used for direct compression.
  • US20100021539A1 relates to a modified release formulation of 1 -[(3-hydroxy- adamant- 1 -ylamino)-acetyl] -pyrrolidine-2(s)-carbonitrile.
  • CN103040759A relates to a sustained-release oral solid preparation by using Vildagliptin as an active component.
  • the oral solid preparation is made by a formulation technique using Vildagliptin as the main component and pharmaceutically acceptable adjuvant, including but not limited to sustained-release matrix tablets, sustained-release diaphragm-con trolled tablets, diaphragm -controlled and matrix sustained-release tablets, and sustained-release capsules prepared from sustained-release particles (pills).
  • Indian Patent application no. 8973/DELNP/2007 relates to a pharmaceutical tablet formulation comprising (a) a compound as an active ingredient; (b) a hydroxypropyl methylcellulose with an apparent viscosity of 80,000cP to 120,000cP (nominal value 10Q,()0QcP) when present in a 1% solution; (c) a microcrystalline cellulose; and (d) a magnesium stearate.
  • Indian Patent application no. 4409/DELNP/2014 describes a pharmaceutical tablet formulation comprising (a) Vildagliptin or the corresponding amount of a pharmaceutically acceptable salt thereof; (b) a hydroxypropyl methylcellulose other than hydroxypropyl methylcellulose K100M with an apparent viscosity of 80,000 cP to 120,000 cP (nominal value 100,000 cP) when present in a 2% solution and optionally a filler and/or a lubricant.
  • a composition comprising Vildagliptinor a pharmaceutically acceptable salt thereof for rapid degradation of the incretin hormones glucagon-like peptide- 1 (GLP-1) and glucose-dependent insulinotropic peptide and improves insulin secretion. It also acts by reducing inappropriate glucagon production, improving insulin sensitivity, improving postprandial lipid and lipoprotein metabolism, and reducing fasting and prandial glucose and HbAlc and reduce hyperglycemia (high blood sugar).
  • GLP-1 glucagon-like peptide- 1
  • HbAlc hyperglycemia
  • the objective of the present invention is to develop an extended release pharmaceutical composition with desired physical and chemical parameters.
  • Another objective of the present invention is to develop a dipeptidyl peptidase IV inhibiting (DPP-IV) pharmaceutical composition with once a day therapeutically effective dosing.
  • DPP-IV dipeptidyl peptidase IV inhibiting
  • Another objective of the present invention is to develop a dipeptidyl peptidase IV inhibiting pharmaceutical composition with increased patient compliance.
  • Another objective of the present invention is to develop extended release dipeptidyl peptidase IV inhibiting (DPP-IV) pharmaceutical composition with desired stability.
  • Yet another objective of the present invention is to develop extended release dipeptidyl peptidase IV inhibiting pharmaceutical composition’s solid dosage forms with desired physical and chemical parameters.
  • the present invention relates to a pharmaceutical composition of Dipeptidyl peptidase- IV (DPP-IV) inhibitors for use in treatment of Diabetes Mellitus (DM). More particularly, the invention relates to a modified release dosage form comprising a composition of Vildagliptin or a pharmaceutically acceptable salt thereof with desired physical and chemical parameters.
  • DPP-IV Dipeptidyl peptidase- IV
  • the invention also provides various formulations and methods of preparing the same.
  • the present invention provides a solid extended release pharmaceutical composition
  • a solid extended release pharmaceutical composition comprising:
  • the present invention further provides a process comprising preparing a tablet dosage form of the pharmaceutical composition, the process comprising:
  • step (b) compressing the tablet formulation obtained in step (a) to form a compressed tablet dosage form.
  • Figurel Illustrates comparative dissolution profile of formulation (F5, F6, F7 and F8) in 0.1N HCl.
  • Figure2 Illustrates comparative dissolution profile of formulation (F5, F6, F7 and F8) in pH 6.8 Phosphate buffer.
  • Figure 3 Illustrates comparative dissolution profile of clinical batches(F9 and FIG) in 0.01 N HCl.
  • Figure 4 illustrates comparative dissolution profile of clinical batches (F9 and FIO) in 0.1 N HCl.
  • Figure 5 Illustrates comparative dissolution profile of clinical batches (F9 and F10) in acetate buffer of pH 4.5.
  • Figure 6 Illustrates comparative dissolution profile of clinical batches (F9 and F10) in phosphate buffer of pH 6.8. DETAILED DESCRIPTION OF THE INVENTION
  • tablets may contain a number of inert materials known as excipients. They may be classified according to the role they play in the final tablet.
  • the primary composition includes filler, binder, lubricant and glidant. Without excipients most drugs and pharmaceutical ingredients cannot be directly- compressed into tablets. This is primarily due to the poor flow and cohesive properties of most drugs.
  • excipients are added to a formulation to impart good flow and compression characteristics to the material being compressed. Such properties are imparted through pretreatment steps, such as wet granulation, slugging, spray drying spheronization or crystallization.
  • the present invention relates to once a day extended release solid dosage form of a pharmaceutical composition comprising a dipeptidyl peptidase IV inhibitor.
  • the dipeptidyl peptidase IV inhibitor (DPP-IV) is useful for preventing or treating diabetes mellitus, non-insulin dependent diabetes mellitus, obesity, arthritis, osteoporosis, and similar diseases.
  • the present invention provides that the dipeptidyl peptidase IV inhibitor is selected from the group consisting of Vildagliptin, Sitagliptin, Saxagliptin, Linagliptin, Gemigliptin, Anagliptin, Teneligliptin, Alogliptin, Trelagliptin, Omarigliptin, Evogliptin, Gasogliptin, Dutogliptin or a pharmaceutically acceptable salt thereof.
  • the dipeptidyl peptidase IV inhibitor is Vildagliptin.
  • the dipeptidyl peptidase IV inhibitor is Vildagliptin.
  • Vildagliptin is readily soluble in water and hence, is rapidly absorbed with more than 90% oral bioavailability. Due to high solubility in water, and rapid absorption, it poses problem is formulating stable extended release formulations of Vildagliptin.
  • the present invention provides stable extended release formulations of Vildagliptin.
  • the present invention relates to an extended release pharmaceutical composition
  • an extended release pharmaceutical composition comprising Vildagliptin in combination with other ingredients which provides a synergistic effect.
  • the present invention relates to a solid dosage form of Vildagliptin pharmaceutical composition which achieves a prolonged therapeutic effect by continuously releasing medication over an extended period after administration of single dose.
  • the present invention relates to development of Vildagliptin matrix based extended release solid dosage form, for the treatment of type 2 diabetes.
  • Compact dosage form is an oral solid dosage form such as tablets which are easy to swallow and more preferably being small in size with length less than 17 mm and width less than 7 mm having shape easier to swallow such as modified oblong.
  • the present invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising of Vildagliptin in combination with hydrophilic polymers to result in a solid dosage form with desired level of stability, dissolution rates, and compact tablet.
  • the present invention describes an extended release stable pharmaceutical solid dosage form containing once a day therapeutically effective dose of Vildagliptin with a combination of hydrophilic polymers with desired physical and chemical parameters.
  • the present invention relates to a stable pharmaceutical solid dosage form comprising of Vildagliptin, hydrophilic release retarding polymers and other excipients.
  • the release retarding polymers are high molecular weight polymers.
  • the present invention relates to a matrix based extended release solid dosage form of Vildagliptin comprising release retarding polymers.
  • the release retarding polymers are high molecular weight (molecular weight of not less than 40,000) hydrophilic release retarding polymers.
  • the hydrophilic release retarding polymer is selected from, but not limited to, methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose (HPMC), sodium carboxymethyl cellulose, polymers of acrylic acid such as Carbomer or a combination thereof.
  • the pharmaceutical composition comprises the high molecular weight hydrophilic polymer in an amount of 10-60% by weight of the composition.
  • the extended release solid dosage forms are prepared by direct compression method using high molecular weight polymers either alone or in combination so as to have compact tablets with good physical properties like flow, wider range of hardness and less friability and a satisfactory impurity data over a stability study.
  • the extended release solid dosage forms are prepared by direct compression method using high molecular weight polymers either alone or in combination so as to have compact tablets which does not show tendency of dose dumping.
  • the extended release solid dosage forms are prepared by direct compression method using hydroxypropyl methyl cellulose polymer with high viscosity of 150,000-280,000 cps based on 2% of solution either alone or in combination so as to have compact tablets which does not show tendency of dose dumping.
  • the pharmaceutical composition of the invention may be formulated in a suitable solid dosage form including, but not limited to, a tablet, caplet, mini-tablet, pellets, granules, capsule, capsule filled with mini-tablets or pellets or combinations thereof.
  • the Vildagliptin pharmaceutical solid dosage form is a compact pharmaceutical tablet formulation with desired physical and chemical parameters.
  • the present invention provides a Vildagliptin pharmaceutical tablet formulation, capable of being compressed, preferably directly compressed, into a tablet having adequate hardne s s/friability, low sensitivity to moisture, improved stability, an acceptable dissolution pattern and improved pharmacokinetic profile in treated patients.
  • the present invention relates to a compact extended release pharmaceutical tablet formulation with desired physical parameters like more compressibility and less friability with expected release profile and acceptable impurity levels at accelerated condition.
  • the extended release tablets are prepared by direct compression method using high molecular weight polymers either alone or in combination to have compact tablets with good physical properties like flow, wider range of hardness and less friability and with acceptable impurity levels.
  • the present invention describes pharmaceutical composition manufactured with direct blending process to form compact pharmaceutical tablets which are easier for administration.
  • the present invention further provides that use of sodium carboxy methyl cellulose as a release retarding polymer not only helps in achieving extended release profile but also helps in improving stability of the product. Further sodium carboxymethyl cellulose alone with combination of two or more different viscosity grades (low viscosity & high viscosity) can help in achieving desired dissolution profile, desired physical andrequired chemical properties.
  • the pharmaceutical composition comprises of the sodium carboxymethyl cellulose with combination of two or more different grades (low viscosity & high viscosity) upto 70% by weight of composition and one or more pharmaceutically acceptable excipients such as fillers, glidants, lubricants, colorants.
  • an extended release pharmaceutical composition comprising:
  • microcrystalline cellulose between 8-10% by weight of composition
  • colloidal silicon dioxide between 0.5-1.0% by weight of composition
  • the pharmaceutical composition comprises of the sodium carboxymethyl cellulose with combination of two or more different grades (low viscosity & high viscosity) upto 70% by weight of composition;
  • microcrystalline cellulose between 8-10% by weight of composition
  • colloidal silicon dioxide between 0.5- 1.0% by weight of composition
  • magnesium stearate between 0.5 -1.0% by weight of composition
  • the pharmaceutical composition comprises of the sodium carboxymethyl cellulose with combination of two or more different grades (low viscosity & high viscosity) upto 70% by weight of composition;
  • the pharmaceutical composition comprises of hydroxypropyl methyl cellulose polymer with viscosity of 150,000-280,000 cps (Methocel K 200 M, Methocel K200 M CR, Hydrocel CW-200000, Benecel K200M pharm) or Hydroxyethyl Cellulose (Natrosol 250 HHX), alone or in combination.
  • the pharmaceutical composition comprises of sodiumcaroboxymethyl cellulose polymer of high viscosity 7500 to 10000 cps for 1% solution (CEKOL 100000), or low viscosity 2500 to 3500 cps for 1% solution (CEKQL 30000 P) or combination thereof.
  • the pharmaceutical composition comprises of hydroxypropyl methyl cellulose polymer with viscosity of 150,000-280,000 cps and hydroxypropyl methyl cellulose polymer with viscosity of 80,000-120,000 cps in combination with a ratio of 5:1 to 1:1, more preferably with a ratio of 3:1 to 2:1 to form a solid dosage form with direct blending which are easy for swallowability.
  • the present invention provides an extended release pharmaceutical composition comprising:
  • hydroxypropyl methylcellulose having viscosity ranging from 150,000 to 280,000 cps
  • hydroxypropyl methylcellulose having viscosity ranging from 80,000 to 120,000 cps
  • microcrystalline cellulose optionally microcrystalline cellulose
  • colloidal silicon dioxide as a glidant
  • hydroxypropyl methylcellulose having viscosity ranging from 150,000 to 280,000cps and that having viscosity ranging from 80,000 to 120,000cps are present in a ratio ranging from 5:1 to 1: 1, more preferably ranging from 3:1 to 2:1.
  • hydroxypropyl methylcellulose having viscosity ranging from 150,000 to 280,000 and that having viscosity ranging from 80,000 to 120,000 ranges are present in a ratio ranging from 5:1 to 1:1, more preferably in a ratio of 3:1.
  • hydroxypropyl methylcellulose having viscosity ranging from 150,000 to 280,000cps and that having viscosity ranging from 80,000 to 120,000cps are present in a ratio ranging from 5:1 to 1:1, more preferably in a ratio of 2:1.
  • vildagliptin in an amount ranging from 26.67% w/w to 33.33% w/w;
  • hydroxypropyl methylcellulose having viscosity ranging from 150,000 to 280,000, in an amount ranging from 24.00% w/w to 30.00% w/w;
  • sodium carboxymethyl cellulose having viscosity ranging from 7500 to 10000 cps for 1% solution, in an amount ranging from 0% w/w to 35.73% w/w;
  • sodium carboxymethyl cellulose having viscosity ranging from 2500 to 3500 cps for 1% solution), in an amount of 0-10.00% w/w;
  • microcrystalline cellulosein an amount ranging from 8.35% w/w to 25.42% w/w; hydroxypropyl cellulose in an amount ranging from3.00% w/w to 3.75% w/w;
  • colloidal silicon dioxide in an amount ranging from 0.50% w/w to 0.62% w/w;
  • magnesium stearate in an amount ranging from 0.50% w/w to 0.62% w/w; and pigment blue in an amount ranging from 1.25% w/w to 1.56% w/w;
  • sodium carboxymethyl cellulose having viscosity ranging from 7500 to 10000 cps for 1% solution and Sodium carboxymethyl cellulose having viscosity ranging from 2500 to 3500 cps for 1% solution are present in a ratio ranging from 5:1 to 1:0.5, and more preferably from 3:1 to 1:0.8.
  • the pharmaceutical composition comprises of hydroxypropyl methyl cellulose polymer with viscosity of 150,000-280,000 cps and high molecular weight (molecular weight of not less than 40,000), sodium carboxy methyl cellulose in combination leading to a solid dosage form which are easier for administration.
  • the invention describes a pharmaceutical solid dosage form manufactured to form a compact tablet with direct blending process having satisfactory physical parameters, comparative dissolution profile (USP type II apparatus with sinkers at 75 rpm in 900 ml at 37°C) as per target.
  • the tablet formulation provides an effective blood concentration for a time period ranging between 15 minutes to 16 hours for Vildagliptin or a pharmaceutically acceptable salt thereof (not more than 30% of Vildagliptin at the end of 15 to 30 minutes; between 35% to 65% of Vildagliptin after 2 hrs or 3 hrs. and not less than 80% of Vildagliptin at the end of 16 hrs.) and satisfactory stability data in terms of acceptable impurity level upon storage at accelerated condition.
  • the present invention also describes pharmaceutical tablet formulation, where in the unit dosage form vildagliptin is present in an amount of 25% weight to 35% weight of the final pharmaceutical composition.
  • the present invention describes a pharmaceutical tablet formulation having tablet hardness and friability in the desired range to obtain the dosage form with acceptable physical and chemical parameters.
  • the present invention describes the pharmaceutical tablet formulation as having tablet hardness in the range of 5-30kg/cm .
  • the hardness is in the range of 7-10 kg/cm 2 , 11-16 kg/cm 2 , 25-29 kg/cm 2 , 15-18 kg/cm 2 , 18-20 kg/cm 2 , or 10-14 kg/cm 2 .
  • One embodiment of the present invention describes the pharmaceutical tablet formulation having friability in the range of 0.01% to 0.5% at 300 rotations.
  • the friability at 300 rotations is 0.334%, 0.088%, or 0.01%.
  • no damage is observed for the pharmaceutical tablet formulation in a friability test conducted at 100 rotations.
  • the pharmaceutical composition is stable and comprises of impurities less than 1.28%.
  • the pharmaceutical composition comprises of impurities less than 0.61%.
  • the pharmaceutical composition comprises of impurities less than 0.58%.
  • the release rate of vildagliptin or a pharmaceutically acceptable salt thereoffrom the tablet formulation is:
  • the present invention describes pharmaceutical tablet formulation comprising 100 mg of Vildagliptin or a salt, wherein;
  • dissolution is measured using a USP type II apparatus with sinkers at 75 rpm in 900 ml at 37°C.
  • the pharmaceutical tablet formulations comprise hydroxypropyl methylcellulose, in an amount ranging from 10% to 60% by weight of the pharmaceutical composition, preferably ranging from 20% to 40% by weight of the pharmaceutical composition. More preferably, the hydroxypropyl methylcellulose is present between 20% by weight and 30% by weight of the pharmaceutical composition.
  • the pharmaceutical tablet formulations comprise hydroxyethyl cellulose, preferably between 20% by weight and 50% by weight of the pharmaceutical composition. More preferably, the hydroxyethyl cellulose is present between 35.73% by weight and 40% by weight of the pharmaceutical composition.
  • the pharmaceutical tablet formulations comprising combination of sodium carboxy methyl cellulose, preferably between 10% by weight and 40% by weight of the pharmaceutical composition and high molecular weight hydroxypropyl methyl cellulose polymer with viscosity of 150,000-280,000 cpspreferably between 20% by weight and 30% by weight of the pharmaceutical composition. More preferably, the sodium carboxy methyl cellulose is present between 10% by weight and 35.73% by weight and high molecular weight hydroxypropyl methyl cellulose polymer with viscosity of 150,000-280,000 cps is present between 24% by weight and 30% by weightof the pharmaceutical composition.
  • the pharmaceutical tablet formulation comprises a high viscosity sodium carboxymethyl cellulose having viscosity ranging from 7500 to 10000 cps for 1% solution or a low viscosity sodium carboxymethyl cellulose having viscosity ranging from 2500 to 3500 cps for 1% solution or a combination thereof; wherein Sodium carboxymethyl cellulose having viscosity ranging from 7500 to 10000 cps for 1% solution and Sodium carboxymethyl cellulose having viscosity ranging from 2500 to 3500 cps for 1% solution are present in the combination in a ratio ranging from 5:1 to 1:0.5, and more preferably from 3:1 to 1 :0.8.
  • the present invention concerns a process for preparing a tablet, in unit dosage form, which comprises:
  • step (b) compressing the tablet formulation obtained in step (a) to form a compressed tablet as unit dosage form.
  • Vildagliptin used throughout the specification refers to not only
  • Formula F3& F4 (With combination of polymers like Hydroxypropyl Methylcellulose, and Hydroxypropyl cellulose)
  • Example 5 refers to clinical study batches of Example 3 (Formula F3&F4) that were taken as per below details:

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  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne une composition pharmaceutique d'inhibiteurs de la dipeptidyl peptidase-IV (DPP-IV) destinée à être utilisée dans le traitement du diabète sucré (DM). Plus particulièrement, la présente invention concerne une forme posologique à libération modifiée ou étendue comprenant une composition de vildagliptine ou un sel pharmaceutiquement acceptable de celle-ci avec des paramètres physiques et chimiques souhaités pour une observance améliorée du patient.
PCT/IN2020/050480 2019-05-29 2020-05-29 Composition pharmaceutique pour le traitement du diabète sucré WO2020240594A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
MX2021014541A MX2021014541A (es) 2019-05-29 2020-05-29 Composicion farmacéutica para diabetes mellitus.
BR112021024099A BR112021024099A2 (pt) 2019-05-29 2020-05-29 Composição farmacêutica para diabetes mellitus
CR20220001A CR20220001A (es) 2019-05-29 2020-05-29 Una composición farmacéutica para la diabetes mellitus
PE2021001978A PE20220644A1 (es) 2019-05-29 2020-05-29 Una composicion farmaceutica para la diabetes mellitus
CONC2021/0018031A CO2021018031A2 (es) 2019-05-29 2021-12-29 Una composición farmacéutica para la diabetes mellitus

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN201921021312 2019-05-29
IN201921021312 2019-05-29

Publications (1)

Publication Number Publication Date
WO2020240594A1 true WO2020240594A1 (fr) 2020-12-03

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BR (1) BR112021024099A2 (fr)
CL (1) CL2021003152A1 (fr)
CO (1) CO2021018031A2 (fr)
CR (1) CR20220001A (fr)
MX (1) MX2021014541A (fr)
PE (1) PE20220644A1 (fr)
WO (1) WO2020240594A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100021539A1 (en) * 2005-06-10 2010-01-28 James Kowalski Modified Release 1-[(3-Hydroxy-Adamant-1-Ylamino)-Acetyl]-Pyrrolidine-2(S)-Carbonitrile Formulation
WO2016016772A1 (fr) * 2014-07-26 2016-02-04 Wockhardt Limited Nouvelle composition pharmaceutique à libération modifiée d'inhibiteurs de la dpp-iv ou de leur sel pharmaceutiquement acceptable

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100021539A1 (en) * 2005-06-10 2010-01-28 James Kowalski Modified Release 1-[(3-Hydroxy-Adamant-1-Ylamino)-Acetyl]-Pyrrolidine-2(S)-Carbonitrile Formulation
WO2016016772A1 (fr) * 2014-07-26 2016-02-04 Wockhardt Limited Nouvelle composition pharmaceutique à libération modifiée d'inhibiteurs de la dpp-iv ou de leur sel pharmaceutiquement acceptable

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CL2021003152A1 (es) 2022-09-23
MX2021014541A (es) 2022-02-11
BR112021024099A2 (pt) 2022-01-11
CO2021018031A2 (es) 2022-04-19
CR20220001A (es) 2022-03-21
PE20220644A1 (es) 2022-04-28

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