WO2022172076A1 - Preparation of microwave dried novel co-processed excipient of sucrose and tablet formulation of canagliflozin tablets using co- processed excipient - Google Patents

Preparation of microwave dried novel co-processed excipient of sucrose and tablet formulation of canagliflozin tablets using co- processed excipient Download PDF

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Publication number
WO2022172076A1
WO2022172076A1 PCT/IB2021/060816 IB2021060816W WO2022172076A1 WO 2022172076 A1 WO2022172076 A1 WO 2022172076A1 IB 2021060816 W IB2021060816 W IB 2021060816W WO 2022172076 A1 WO2022172076 A1 WO 2022172076A1
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processed
sucrose
excipient
pharmaceutical excipient
granules
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PCT/IB2021/060816
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French (fr)
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Shailendra Mandge
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DWIVEDI, Dr. Jayesh
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    • 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
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • 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
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof

Definitions

  • the embodiment herein generally relates to a co-processed excipient of sucrose, its preparation and its use in composition, wherein said co-processed pharmaceutical excipient of sucrose prepared using different ratios or percentage of approved pharmaceutical excipients.
  • Excipient is an inactive substance that serves as the vehicle or medium for a drug or other active substance. These can be things like coloring agents, preservatives and fillers.
  • An excipient is formulated alongside the active ingredient of a medication, included for the purpose of long term stabilization, bulking up solid formulation that contain potent active ingredients in small amounts or to confer a therapeutic enhancement on the active ingredient in the final dosage form, such as facilitating drug adsorption, reducing viscosity or enhancing solubility.
  • Sucrose is a non-reducing crystalline disaccharide made up of glucose and fructose. Sucrose is commonly used in the biopharmaceutical industry to stabilize proteins, lipids and carbohydrates during the formulation process. The utility and function is driven by its unique chemical and physical properties, especially in aqueous solutions.
  • compositions are the vital components of drug formulations and play a significant role in any dosage form.
  • Pharmaceutical excipients can be considered an indispensable part of pharmaceutical products. In most formulations, they are present in a more substantial proportion compare to active pharmaceutical ingredients or API, so it is always necessary to select an excipient that substantiates the ideal properties for an excipient.
  • excipients are engineered to achieve the properties of the tableting’s critical components blend in a single, highly flowable, and compressible granular or microgranular material.
  • the co-processed excipient combines two or more compendial or non- compendial excipients designed to physically modify their properties, which cannot be achieved by simple physical mixing and without significant chemical changes.
  • a main object of the present invention is to develop a co-processed excipient which is ready to be used excipient.
  • Another object of the present invention is to develop a co-processed pharmaceutical excipient of Dicalcium phosphate, Corn starch, Sucrose, Calcium silicate, Providone, Croscarmellose Sodium and Microcrystalline cellulose.
  • Another object of the present invention is to develop a co-processed excipient which provides high functionality compare to the individual excipients.
  • Still another object of the present invention is to develop a co-processed excipient which possesses improved flow properties.
  • Yet another object of the present invention is to develop a co-processed excipient which possesses improved compressibility.
  • Another object of the present invention is to develop a co-processed excipient which has a better dilution potential.
  • Another object of the present invention is to develop a co-processed excipient which has a lesser weight variation during direct compression.
  • Still another object of the present invention is to develop a co-processed excipient which has reduced lubricant sensitivity.
  • Yet another object of the present invention is to reduce development time lines and process validation efforts. [00020]
  • the other objects and advantages of the present invention will be apparent from the following description when read in conjunction with the accompanying drawings, which are incorporated for illustration of preferred embodiments of the present invention and are not intended to limit the scope thereof.
  • an embodiment herein provides a method 1000 of preparation of microwave dried novel co-processed excipient of Sucrose using a co-processed mixture of Di calcium phosphate, com starch, sucrose, calcium silicate, Povidone and microcrystalline cellulose.
  • the method 1000 of preparation of microwave dried novel co-processed excipient of Sucrose uses a co-processed mixture of Di calcium phosphate, corn starch, sucrose, calcium silicate, Povidone and microcrystalline cellulose.
  • the method comprises the steps of: dissolving 1001 the required amount of Sucrose and Povidone in purified water with slow stirring to make the binder solution of the desired concentration; weighing 1002 the required quantity of di calcium phosphate, corn starch, crosscarmellose sodium and calcium silicate mix and sift through ASTM# 20; performing 1003 the granulation using the binder solution followed by the wet sifting using a 0.8 mm sieve; drying 1004 the granules obtained in a microwave with 100% power; sifting 1005 the dried granules using 0.8mm sieve; packing 1006 the granules in a double polybag using silica sachets; and blending 1007 the granules with micro crystalline cellulose in the desired
  • Fig.1 illustrates Differential Scanning Calorimetry (DSC) data of Sucrose, according to an embodiment herein;
  • Fig.2 illustrates Differential Scanning Calorimetry (DSC) data of Granules used in co-processed excipient, according to an embodiment herein;
  • Fig.3 illustrates pXRD of Granules used in co-processed excipient, according to an embodiment herein;
  • Fig.4 illustrates pXRD of Sucrose, according to an embodiment herein
  • Fig.5 illustrates SEM image of granules used in co-processed excipient at a magnification of x250, according to an embodiment herein
  • Fig.6 illustrates SEM image of granules used in co-processed excipient at a magnification of x500, according to an embodiment herein;
  • Fig.7 illustrates SEM image of granules used in co-processed excipient at a magnification of xl500, according to an embodiment herein;
  • Fig.8 illustrates SEM image of granules used in co-processed excipient at a magnification of x5000, according to an embodiment herein;
  • Fig 9 illustrates comparison of Tablet dissolution performed in release media,Water+0.75% SLS, paddle, 75 rpm, 600 mL with the reference product, Invokana (Mfg. by- Janssen Pharmaceuticals, Inc., USA); and [00034] Fig. 10 illustrates the steps in the method of preparation of microwave dried novel co-processed excipient of Sucrose, according to an embodiment herein.
  • the process for preparation of co-processed pharmaceutical excipient comprises the steps of: l.Wet granulation followed by microwave drying; and 2. a blending of step 1 dried granules with Microcrystalline cellulose.
  • the invention is illustrated by the following examples which are only meant to illustrate the invention and not act as limitations. All embodiments apparent to the process in the art are deemed to fall within the scope of the present invention.
  • the Example 1 depicts the formulation of the granules in the below Table 1.
  • the manufacturing process 1000 comprises of the following steps: dissolving 1001 the required amount of Sucrose and Povidone in purified water with slow stirring to make the binder solution of the desired concentration; weighing 1002 the required quantity of di calcium phosphate, corn starch, crosscarmellose sodium and calcium silicate mix and sift through ASTM# 20; performing 1003 the granulation using the binder solution followed by the wet sifting using a 0.8 mm sieve; drying 1004 the granules obtained in a microwave with 100% power; sifting 1005 the dried granules using 0.8mm sieve; packing 1006 the granules in a double polybag using silica sachets; and blending 1007 the granules with micro crystalline cellulose in the desired ratio to make the final co-processed pharmaceutical excipient.
  • the granules characteristics of the Example 1 are depicted in the below mentioned Table 2.
  • Example 2 describes the final blending composition of the tablet in Table 3 mentioned below.
  • Tablet characteristics of Example 2 are mentioned in the below mentioned Table 4.
  • Example 3 shows the design of the experimental trials.
  • Table 5 shows the excipient composition of the granules.
  • Table 5 [00048] According to an embodiment, Table 6 below depicts granules characteristics of Example 3.
  • Table 6 means ‘not acceptable’, ‘+’ means ‘Fine and dusty’, ‘++’ means ‘Moderate’, ‘+++’ means ‘Excellent’.
  • Table 7 depicts tablets characteristics of Example 3.
  • granule data and Compression data for example, 3 indicates that co-processed pharmaceutical excipients show significant improvements.
  • the data of carr’s index, porosity, Hausner's ratio, and angle of repose proves that the co-processed pharmaceutical excipients as per the present invention were having good compressibility and flow property.
  • Fig.l illustrates Differential Scanning Calorimetry of Sucrose, according to an embodiment herein.
  • DSC Differential scanning calorimetry
  • pXRD pXRD data of the granules revealed that the granules are in an amorphous state, and no crystalline peak of sucrose was observed (Fig. 1-4).
  • the amorphous state of sucrose helped in compression and fast disintegration, while sucrose's crystallinity compromises the compaction behavior.
  • Fig 4-8 depict SEM images show the porous structure of the co-processed pharmaceutical excipients.
  • the tablet formulation of Canagliflozin tablets, lOOmg was done using co-processed excipient of sucrose.
  • granules were prepared and blended with microcrystalline cellulose to make the final co processed pharmaceutical excipient.
  • the canagliflozin tablet 100 mg was prepared using a co-processed pharmaceutical excipient depicted in Table 8 and compared the physical parameters and dissolution with the reference product Invokana (Mfg. by- Janssen Pharmaceuticals, Inc., USA) as mentioned in Table 9.
  • Invokana Mfg. by- Janssen Pharmaceuticals, Inc., USA
  • Table 8 the Table 8 below mentions about the canagliflozin Tablet Composition.
  • Table 8 [00060] According to an embodiment, the Table 9 below mentions about comparative tablet physical parameters and dissolution with the reference product Invokana (Mfg. by- Janssen Pharmaceuticals, Inc., USA)
  • Fig. 9 depicts Tablet dissolution performed in release media, Water+0.75% SLS, paddle, 75 rpm, 600 mL and compared with the reference product, Invokana (Mfg. by- Janssen Pharmaceuticals, Inc., USA).
  • a main advantage of the present invention is that it provides a co- processed excipient which is ready to be used excipient.
  • Another advantage of the present invention is that the process is simple and cost effective.
  • Still another advantage of the present invention is that the provided co processed excipient shows high functionality compare to the individual excipients. [00065] Yet another advantage of the present invention is that the co-processed excipient possesses improved flow properties.
  • Another advantage of the present invention is that the provided the co processed excipient possesses improved compressibility.
  • Another advantage of the present invention is that the provided the co- processed excipient possesses better dilution potential.
  • Another advantage of the present invention is that the provided the co processed excipient possesses properties of the tableting’s critical components blend in a single, highly flowable, and compressible granular or microgranular material.

Abstract

A method 1000 of preparation of microwave dried novel co-processed excipient of Sucrose using a co-processed mixture of Di calcium phosphate, corn starch, sucrose, calcium silicate, Povidone and microcrystalline cellulose. The method comprises the steps of: dissolving 1001 the required amount of Sucrose and Povidone in purified water with slow stirring to make the binder solution of the desired concentration; weighing 1002 the required quantity of di calcium phosphate, corn starch, crosscarmellose sodium and calcium silicate mix and sift through ASTM# 20; performing 1003 the granulation using the binder solution followed by the wet sifting using a 0.8 mm sieve; drying 1004 the granules obtained in a microwave with 100% power; sifting 1005 the dried granules using 0.8mm sieve; packing 1006 the granules in a double polybag using silica sachets; and blending 1007 the granules with micro crystalline cellulose in the desired ratio to make the final co-processed pharmaceutical excipient.

Description

PREPARATION OF MICROWAVE DRIED NOVEL COPROCESSED EXCIPIENT OF SUCROSE AND TABLET FORMULATION OF CANAGLIFLOZIN TABLETS USING COPROCESSED EXCIPIENT FIELD OF INVENTION
[0001] The embodiment herein generally relates to a co-processed excipient of sucrose, its preparation and its use in composition, wherein said co-processed pharmaceutical excipient of sucrose prepared using different ratios or percentage of approved pharmaceutical excipients. BACKGROUND AND PRIOR ART
[0002] Excipient is an inactive substance that serves as the vehicle or medium for a drug or other active substance. These can be things like coloring agents, preservatives and fillers.
[0003] An excipient is formulated alongside the active ingredient of a medication, included for the purpose of long term stabilization, bulking up solid formulation that contain potent active ingredients in small amounts or to confer a therapeutic enhancement on the active ingredient in the final dosage form, such as facilitating drug adsorption, reducing viscosity or enhancing solubility.
[0004] Sucrose is a non-reducing crystalline disaccharide made up of glucose and fructose. Sucrose is commonly used in the biopharmaceutical industry to stabilize proteins, lipids and carbohydrates during the formulation process. The utility and function is driven by its unique chemical and physical properties, especially in aqueous solutions.
[0005] Pharmaceutical excipients are the vital components of drug formulations and play a significant role in any dosage form. Pharmaceutical excipients can be considered an indispensable part of pharmaceutical products. In most formulations, they are present in a more substantial proportion compare to active pharmaceutical ingredients or API, so it is always necessary to select an excipient that substantiates the ideal properties for an excipient.
[0006] Developing new excipients and conventionally using a blend of excipients can be time-consuming and expensive from a safety and processing perspective; hence, co-processing already approved excipients is an attractive alternative.
[0007] These excipients are engineered to achieve the properties of the tableting’s critical components blend in a single, highly flowable, and compressible granular or microgranular material. [0008] The co-processed excipient combines two or more compendial or non- compendial excipients designed to physically modify their properties, which cannot be achieved by simple physical mixing and without significant chemical changes.
[0009] Therefore, there is a need to develop co-processed excipients which are ready to be used excipients, provide high functionality compare to the individual excipients which could directly be used in the formulation and does not require RMG/FBG granulation, spray drying or any other technique for the finished dosage form.
OBJECTS OF THE INVENTION [00010] Some of the objects of the present disclosure are described herein below:
[00011] A main object of the present invention is to develop a co-processed excipient which is ready to be used excipient.
[00012] Another object of the present invention is to develop a co-processed pharmaceutical excipient of Dicalcium phosphate, Corn starch, Sucrose, Calcium silicate, Providone, Croscarmellose Sodium and Microcrystalline cellulose. [00013] Another object of the present invention is to develop a co-processed excipient which provides high functionality compare to the individual excipients. [00014] Still another object of the present invention is to develop a co-processed excipient which possesses improved flow properties. [00015] Yet another object of the present invention is to develop a co-processed excipient which possesses improved compressibility.
[00016] Another object of the present invention is to develop a co-processed excipient which has a better dilution potential.
[00017] Another object of the present invention is to develop a co-processed excipient which has a lesser weight variation during direct compression.
[00018] Still another object of the present invention is to develop a co-processed excipient which has reduced lubricant sensitivity.
[00019] Yet another object of the present invention is to reduce development time lines and process validation efforts. [00020] The other objects and advantages of the present invention will be apparent from the following description when read in conjunction with the accompanying drawings, which are incorporated for illustration of preferred embodiments of the present invention and are not intended to limit the scope thereof.
SUMMARY OF THE INVENTION
[00021] In view of the foregoing, an embodiment herein provides a method 1000 of preparation of microwave dried novel co-processed excipient of Sucrose using a co-processed mixture of Di calcium phosphate, com starch, sucrose, calcium silicate, Povidone and microcrystalline cellulose.
[00022] The method 1000 of preparation of microwave dried novel co-processed excipient of Sucrose uses a co-processed mixture of Di calcium phosphate, corn starch, sucrose, calcium silicate, Povidone and microcrystalline cellulose. The method comprises the steps of: dissolving 1001 the required amount of Sucrose and Povidone in purified water with slow stirring to make the binder solution of the desired concentration; weighing 1002 the required quantity of di calcium phosphate, corn starch, crosscarmellose sodium and calcium silicate mix and sift through ASTM# 20; performing 1003 the granulation using the binder solution followed by the wet sifting using a 0.8 mm sieve; drying 1004 the granules obtained in a microwave with 100% power; sifting 1005 the dried granules using 0.8mm sieve; packing 1006 the granules in a double polybag using silica sachets; and blending 1007 the granules with micro crystalline cellulose in the desired ratio to make the final co-processed pharmaceutical excipient.
[00023] These and other aspects of the embodiments herein will be better appreciated and understood when considered in conjunction with the following description and the accompanying drawings. It should be understood, however, that the following descriptions, while indicating preferred embodiments and numerous specific details thereof, are given by way of illustration and not of limitation. Many changes and modifications may be made within the scope of the embodiments herein without departing from the spirit thereof, and the embodiments herein include all such modifications. BRIEF DESCRIPTION OF DRAWINGS
[00024] The detailed description is set forth with reference to the accompanying figures. In the figures, the left-most digit(s) of a reference number identifies the figure in which the reference number first appears. The use of the same reference numbers in different figures indicates similar or identical items.
[00025] Fig.1 illustrates Differential Scanning Calorimetry (DSC) data of Sucrose, according to an embodiment herein;
[00026] Fig.2 illustrates Differential Scanning Calorimetry (DSC) data of Granules used in co-processed excipient, according to an embodiment herein; [00027] Fig.3 illustrates pXRD of Granules used in co-processed excipient, according to an embodiment herein;
[00028] Fig.4 illustrates pXRD of Sucrose, according to an embodiment herein; [00029] Fig.5 illustrates SEM image of granules used in co-processed excipient at a magnification of x250, according to an embodiment herein; [00030] Fig.6 illustrates SEM image of granules used in co-processed excipient at a magnification of x500, according to an embodiment herein;
[00031] Fig.7 illustrates SEM image of granules used in co-processed excipient at a magnification of xl500, according to an embodiment herein;
[00032] Fig.8 illustrates SEM image of granules used in co-processed excipient at a magnification of x5000, according to an embodiment herein;
[00033] Fig 9 illustrates comparison of Tablet dissolution performed in release media,Water+0.75% SLS, paddle, 75 rpm, 600 mL with the reference product, Invokana (Mfg. by- Janssen Pharmaceuticals, Inc., USA); and [00034] Fig. 10 illustrates the steps in the method of preparation of microwave dried novel co-processed excipient of Sucrose, according to an embodiment herein.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS [00035] The embodiments herein and the various features and advantageous details thereof are explained more fully with reference to the non-limiting embodiments and detailed in the following description. Descriptions of well- known components and processing techniques are omitted so as to not unnecessarily obscure the embodiments herein. The examples used herein are intended merely to facilitate an understanding of ways in which the embodiments herein may be practiced and to further enable those of skill in the art to practice the embodiments herein. Accordingly, the examples should not be construed as limiting the scope of the embodiments herein.
[00036] As mentioned above, there is a need to develop a co-processed pharmaceutical excipient which is engineered to achieve the properties of the tableting’s critical components blend in a single, highly flowable, and compressible granular or microgranular material. The embodiments herein achieve this by preparing a co-processed pharmaceutical excipient of Dicalcium phosphate, Com starch, Sucrose, Calcium silicate, Povidone, Croscarmellose Sodium, and Microcrystalline cellulose.
[00037] According to an embodiment, the process for preparation of co-processed pharmaceutical excipient comprises the steps of: l.Wet granulation followed by microwave drying; and 2. a blending of step 1 dried granules with Microcrystalline cellulose. [00038] The invention is illustrated by the following examples which are only meant to illustrate the invention and not act as limitations. All embodiments apparent to the process in the art are deemed to fall within the scope of the present invention. [00039] According to an embodiment, the Example 1 depicts the formulation of the granules in the below Table 1.
Figure imgf000009_0001
Table 1
[00040] According to an embodiment, as mentioned in the Fig. 10 the manufacturing process 1000 comprises of the following steps: dissolving 1001 the required amount of Sucrose and Povidone in purified water with slow stirring to make the binder solution of the desired concentration; weighing 1002 the required quantity of di calcium phosphate, corn starch, crosscarmellose sodium and calcium silicate mix and sift through ASTM# 20; performing 1003 the granulation using the binder solution followed by the wet sifting using a 0.8 mm sieve; drying 1004 the granules obtained in a microwave with 100% power; sifting 1005 the dried granules using 0.8mm sieve; packing 1006 the granules in a double polybag using silica sachets; and blending 1007 the granules with micro crystalline cellulose in the desired ratio to make the final co-processed pharmaceutical excipient.
[00041] According to an embodiment, the granules characteristics of the Example 1 are depicted in the below mentioned Table 2.
Figure imgf000010_0001
Table 2
[00042] According to an embodiment, based on granules characterization, tablet compression was done for selected formulations. For tablet compression, granules are blended with microcrystalline cellulose in 40:60 ratio to make the final pharmaceutical co-processed excipient. The croscarmellose sodium and Magnesium stearate kept constant, i.e., 5.5% w/w for all tablet compositions. [00043] According to an embodiment, Example 2 describes the final blending composition of the tablet in Table 3 mentioned below.
Figure imgf000010_0002
[00044] According to an embodiment, tablets characteristics of Example 2 are mentioned in the below mentioned Table 4.
Figure imgf000011_0001
Table 4
[00045] According to an embodiment, based on the Example 1, the following ranges of excipients were identified and experiments were conducted. The percentage of croscarmellose sodium and providone kept constant for all the trials. [00046] According to an embodiment, the Example 3 shows the design of the experimental trials.
[00047] According to an embodiment, Table 5 below shows the excipient composition of the granules.
Figure imgf000011_0002
Table 5 [00048] According to an embodiment, Table 6 below depicts granules characteristics of Example 3.
Figure imgf000012_0001
Table 6
[00049] According to an embodiment, in Table 6 means ‘not acceptable’, ‘+’ means ‘Fine and dusty’, ‘++’ means ‘Moderate’, ‘+++’ means ‘Excellent’.
[00050] According to an embodiment, Table 7 depicts tablets characteristics of Example 3.
Figure imgf000012_0002
Table 7
[00051] According to an embodiment, granule data and Compression data, for example, 3 indicates that co-processed pharmaceutical excipients show significant improvements. The data of carr’s index, porosity, Hausner's ratio, and angle of repose proves that the co-processed pharmaceutical excipients as per the present invention were having good compressibility and flow property.
[00052] Referring now to the drawings, and more particularly to FIGS. 1 through 9, where similar reference characters denote corresponding features consistently throughout the figures, there are shown preferred embodiments. [00053] Fig.l illustrates Differential Scanning Calorimetry of Sucrose, according to an embodiment herein. [00054] According to an embodiment, Differential scanning calorimetry (DSC) and pXRD data of the granules revealed that the granules are in an amorphous state, and no crystalline peak of sucrose was observed (Fig. 1-4). The amorphous state of sucrose helped in compression and fast disintegration, while sucrose's crystallinity compromises the compaction behavior.
[00055] According to an embodiment, Fig 4-8 depict SEM images show the porous structure of the co-processed pharmaceutical excipients.
[00056] According to an embodiment, the tablet formulation of Canagliflozin tablets, lOOmg was done using co-processed excipient of sucrose. [00057] According to an embodiment, based on Example 3, granules were prepared and blended with microcrystalline cellulose to make the final co processed pharmaceutical excipient.
[00058] According to an embodiment, the canagliflozin tablet, 100 mg was prepared using a co-processed pharmaceutical excipient depicted in Table 8 and compared the physical parameters and dissolution with the reference product Invokana (Mfg. by- Janssen Pharmaceuticals, Inc., USA) as mentioned in Table 9. [00059] According to an embodiment, the Table 8 below mentions about the canagliflozin Tablet Composition.
Figure imgf000013_0001
Table 8 [00060] According to an embodiment, the Table 9 below mentions about comparative tablet physical parameters and dissolution with the reference product Invokana (Mfg. by- Janssen Pharmaceuticals, Inc., USA)
Figure imgf000014_0001
Table 9 [00061] According to an embodiment, the Fig. 9 depicts Tablet dissolution performed in release media, Water+0.75% SLS, paddle, 75 rpm, 600 mL and compared with the reference product, Invokana (Mfg. by- Janssen Pharmaceuticals, Inc., USA).
[00062] A main advantage of the present invention is that it provides a co- processed excipient which is ready to be used excipient.
[00063] Another advantage of the present invention is that the process is simple and cost effective.
[00064] Still another advantage of the present invention is that the provided co processed excipient shows high functionality compare to the individual excipients. [00065] Yet another advantage of the present invention is that the co-processed excipient possesses improved flow properties.
[00066] Another advantage of the present invention is that the provided the co processed excipient possesses improved compressibility.
[00067] Another advantage of the present invention is that the provided the co- processed excipient possesses better dilution potential. [00068] Another advantage of the present invention is that the provided the co processed excipient possesses properties of the tableting’s critical components blend in a single, highly flowable, and compressible granular or microgranular material. [00069] The foregoing description of the specific embodiments will so fully reveal the general nature of the embodiments herein that others can, by applying current knowledge, readily modify and/or adapt for various applications such specific embodiments without departing from the generic concept, and, therefore, such adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation. Therefore, while the embodiments herein have been described in terms of preferred embodiments, those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope of the embodiments as described herein.

Claims

im:
1. A method 1000 of preparation of microwave dried novel co-processed excipient of Sucrose, wherein the method comprises the steps of: dissolving 1001 the required amount of Sucrose and Povidone in purified water with slow stirring to make the binder solution of the desired concentration; weighing 1002 the required quantity of di calcium phosphate, corn starch, crosscarmellose sodium and calcium silicate mix and sift through ASTM# 20; performing 1003 the granulation using the binder solution followed by the wet sifting using a 0.8 mm sieve; drying 1004 the granules obtained in a microwave with 100% power; sifting 1005 the dried granules using 0.8mm sieve; packing 1006 the granules in a double polybag using silica sachets; and blending 1007 the granules with micro crystalline cellulose in the desired ratio to make the final co-processed pharmaceutical excipient; characterized in that wherein the method uses a co-processed mixture of Di calcium phosphate, com starch, sucrose, calcium silicate, Povidone and microcrystalline cellulose; and wherein the di-calcium present in the range of 30 to 70% w/w, corn starch present in the range of 30 to 70% w/w, sucrose present in the range of 40 to 60% w/w, calcium silicate present in the range of 40 to 60% w/w, and MCC present in the range of 10 to 90% w/w of the total weight of co processed excipient.
2. The co-processed pharmaceutical excipient as claimed in claim 1 wherein the ratio of Di calcium phosphate to com starch is in the range of 30:70 % to 70:30% w/w.
3. The co-processed pharmaceutical excipient as claimed in claim 1 wherein the ratio of Sucrose to calcium silicate is in the range of 40:60% to 60:40% w/w.
4. The co-processed pharmaceutical excipient as claimed in claim 1 wherein the ratio of Sucrose to povidone is in the range of 50:50% to 40:60% w/w.
5. The co-processed pharmaceutical excipient as claimed in claim 1 wherein the ratio of Granules to Microcrysatlline is in the range of 10:90% to 90:10% w/w.
6. The co-processed pharmaceutical excipient as claimed in claim 1 wherein the Binder concentration is in the range of 10 to 20 % w/w.
7. The co-processed pharmaceutical excipient as claimed in claim 1, wherein the co-processed pharmaceutical excipient further comprises one or more pharmaceutically acceptable excipients.
8. The co-processed pharmaceutical excipient as claimed in claim 8, wherein one or more pharmaceutically acceptable excipients selected from the binder, disintegrating agent, glidant, or sweetener category.
9. The method for producing a co-processed pharmaceutical excipient as claimed in claim 1, wherein co-processing involves wet granulation and microwave-assisted drying followed by blending.
10. The method for producing a co-processed pharmaceutical excipient as claimed in claim 10, wherein the exhaust temperature during drying is not more than 50°C or 122°F in microwave-assisted drying.
11. The co-processed pharmaceutical excipient as claimed in claim 1, wherein the sucrose essentially is in the amorphous state.
12. A pharmaceutical composition with optimal mechanical strength, wherein the composition comprising; at least one active pharmaceutical or nutraceutical ingredient; a co-processed pharmaceutical excipient comprising Dicalcium phosphate, Corn starch, Sucrose, Calcium silicate, Povidone, Croscarmellose Sodium, and Microcrystalline cellulose; and one or more pharmaceutically acceptable excipients.
PCT/IB2021/060816 2021-02-09 2021-11-22 Preparation of microwave dried novel co-processed excipient of sucrose and tablet formulation of canagliflozin tablets using co- processed excipient WO2022172076A1 (en)

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Citations (1)

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Publication number Priority date Publication date Assignee Title
US20170281609A1 (en) * 2016-03-29 2017-10-05 Hoffmann-La Roche Inc. Granulate Formulation of 5-methyl-1-phenyl-2-(1H)-pyridone and Method of Making the Same

Patent Citations (1)

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Publication number Priority date Publication date Assignee Title
US20170281609A1 (en) * 2016-03-29 2017-10-05 Hoffmann-La Roche Inc. Granulate Formulation of 5-methyl-1-phenyl-2-(1H)-pyridone and Method of Making the Same

Non-Patent Citations (1)

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Title
AL-ALI MAHA, SALIH KUTAIBA I., ALSAMARRAE ABDULQAHAR: "Microwave heating temperatures and pharmaceutical powder characteristics", MATERIALS TODAY: PROCEEDINGS, ELSEVIER, NL, vol. 20, 1 January 2020 (2020-01-01), NL , pages 583 - 587, XP055963161, ISSN: 2214-7853, DOI: 10.1016/j.matpr.2019.09.193 *

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