DESC:, a disintegrant, a
binder and a lubricant.
WO 2016/030502A discloses a formulation comprising a nonstoichiometric
hydrate of canagliflozin or an amorphous canagliflozin, and at
least one of excipients, wherein the formulation is defined by a water activity of
< 0.4, determined at room temperature.
However, there still remains a need in the art for novel pharmaceutical
formulations of amorphous canagliflozin.
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SUMMARY OF INVENTION
The present invention relates to pharmaceutical formulations of
amorphous canagliflozin.
An aspect relates to pharmaceutical formulation comprising amorphous
canagliflozin prepared by dry granulation process.
A further aspect relates to pharmaceutical formulation comprising
amorphous canagliflozin prepared by hot melt extrusion process.
A further aspect relates to pharmaceutical formulation comprising
amorphous canagliflozin prepared by wet granulation process.
A further aspect relates to pharmaceutical formulation comprising
amorphous canagliflozin prepared by direct compression process.
A further aspect relates to pharmaceutical bi-layer formulation comprising
amorphous canagliflozin.
An embodiment relates to a pharmaceutical formulation mentioned in
any of the above, additionally contain surfactant.
DETAILED DESCRIPTION
As used herein, the term “surfactant” may include an anionic, a cationic,
a zwitterionic or a non-ionic surfactant. The surfactant of the present invention
may also be a mixture of two or more surfactants. Surfactant may include
sodium lauryl sulfate, polaxomer, cremophors, tween, span, polyethylene
glycol, polyethylene glycol fatty acid esters, polyethylene glycol sorbitan fatty
acid esters, sodium oleate, sodium lauryl sarcosinate, sodium dioctyl
sulfosuccinate, sodium myristate, sodium palmitate, sodium state, sodium
ricinoleate, bile salts such as sodium cholate, sodium taurocholate, sodium
glycocholate and the like.
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As used herein, the term “granulating solvent” may include aqueous and
non- aqueous solvents. Non aqueous solvents may include acetone, ethanol,
methanol, isopropyl alcohol, Dimethylsulfoxide, hexane, propylene glycol,
polyethylene glycol and the like.
In the pharmaceutical formulations of present invention, canagliflozin
may be contained in an amount of 50 mg to 500 mg.
In the pharmaceutical formulations of present invention, particle size D90
of the amorphous canagliflozin may be 1 micron to 200 micron, preferably 5
micron to 40 micron.
As used herein, the term “pharmaceutical formulation” may include solid
dosage forms suitable for oral administration such as tablets, capsules, pills,
films, caplets, granules, pellets and the like. The tablet may be an immediate
release tablet, a delayed release tablet, a modified release tablet, a chewable
tablet, a confectionary tablet, an oral disintegrating tablet. These solid dosage
forms may be coated with sugar coating or film coating with the aim of, for
example, preventing abrasion wear and improving stability.
As used herein, the term “pharmaceutically acceptable excipient” include
any such materials known in the art that are nontoxic and do not interact with
other components of a pharmaceutical formulation in a deleterious manner.
According to the present invention “pharmaceutical acceptable excipient”
include, for example, diluent, binder, disintegrant, lubricant and glidant that are
useful in preparation of pharmaceutical formulation. Pharmaceutically
acceptable excipients may be used as intra granular or extra granular
excipients.
An embodiment of present invention relates to pharmaceutical
formulation comprising amorphous canagliflozin prepared by dry granulation
process
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An embodiment of present invention relates to pharmaceutical
formulation comprising amorphous canagliflozin prepared by hot melt extrusion
process
An embodiment of present invention relates to pharmaceutical
formulation comprising amorphous canagliflozin prepared by wet granulation
process
An embodiment of present invention relates to pharmaceutical
formulation comprising amorphous canagliflozin prepared by direct
compression process
An embodiment of present invention relates to pharmaceutical bi-layer
formulation comprising amorphous canagliflozin
An embodiment of present invention relates to pharmaceutical
formulation comprising amorphous canagliflozin with particle size D90 of 5
micron to 40 micron.
An embodiment relates to a pharmaceutical formulation mentioned in
any of the above, additionally contain surfactant.
An embodiment relates to a pharmaceutical formulation mentioned in
any of the above; additionally contain one or more pharmaceutically acceptable
excipients.
Tablets may be manufactured by blending amorphous canagliflozin, one
or more pharmaceutically acceptable excipient followed by compression as in
the case of direct compression.
Granules of amorphous canagliflozin may be prepared by any one of
known methods such as wet/spray granulation, dry granulation, hot melt
granulation and the like. Tablets may be manufactured after adding extra
granular excipients to these granules followed by compression. The tableting
machine capable of compressing bi-layered tablets may be used.
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Tablet formulations may be film coated with non-functional polymer for
the purpose of preventing abrasion wear, masking bitterness, improving
stability, and the like.
The present invention relates to preparation of pharmaceutical
formulation by dry granulation process, wherein the process comprises the
steps of:
a) Blending amorphous canagliflozin and one or more intra granular
pharmaceutically acceptable excipients;
b) Granulating the blend of using roll compactor, an oscillating granulator etc.
c) Blending the granules of with extra granular excipients;
d) Compressing the blend into tablets and optionally film coated.
The present invention relates to preparation of pharmaceutical
formulation by hot melt granulation process, wherein the process comprises the
steps of:
a) Blending amorphous canagliflozin, and one or more intra granular
pharmaceutically acceptable excipients;
b) Granulating the blend using twin screw extrusion apparatus with use of chiller
if required;
c) Blending the granules with extra granular excipients;
d) Compressing the blend of into tablets and optionally film coated.
The present invention relates to preparation of a pharmaceutical
formulation by wet/spray granulation, wherein the process comprises the steps
of:
a) Blending all intra granular pharmaceutically acceptable excipients optionally
along with amorphous canagliflozin;
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b) Dissolving the binder and optionally amorphous canagliflozin in non-aqueous
granulating solvent;
c) Granulating the blend using binder solution;
d) Blending the granules with extra granular excipients;
e) Compressing the blend into tablets and optionally film coated.
The present invention relates to preparation of pharmaceutical bi-layer
formulation, wherein the process comprises the steps of:
a) Blending amorphous canagliflozin, and one or more intra granular
pharmaceutically acceptable excipients;
b) Dissolving binder in granulating solvent;
c) Granulating the blend using binder solution;
d) Blending remaining all pharmaceutically acceptable excipients;
e) Step (c) and step (d) were compressed into bi-layer tablets and optionally
film coated.
A further embodiment of present invention, may additionally contain
surfactant in any of the above inventions related to process
While this invention has been described with reference to specific
embodiments, the scope of the invention is not limited to these embodiments
alone. Further some of the embodiments are illustrated as working examples
below and are meant to be representative only. The invention may be construed
in any other forms and embodiments which may be understood and applied by
a person skilled in the art within the scope of the present invention.
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Examples:
Unit Composition Details
S. No. Name of the Ingredient
Example 1 Example 2 Example 3
Example
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mg/ tab mg/tab mg/tab mg/tab
1 Canagliflozin (amorphous) 300.00 300.00 300.00 300.00
2 Acetone/ DCM/
Ethanol/Methanol
NA NA q.s. NA
3 Microcrystalline cellulose /
Mannitol/ Lactose/calcium
phosphate etc.
217.56 217.56 222.00 187.56
4 Sodium starch glycolate/
Croscarmellose sodium/
Crospovidone etc.
54.00 54.00 49.56 30.00
5 Hydroxypropyl cellulose/
Hydroxypropyl methyl
cellulose
NA NA 18.00 18.00
6 Sodium lauryl sulphate/
Polaxomer/Polyethylene
glycol
NA NA NA 30.00
7 Colloidal silicon dioxide/
Syloid/ Talc etc.
24.00 24.00 6.00 30.00
8 Magnesium stearate 4.44 4.44 4.44 4.44
Uncoated tablet weight 600.00 600.00 600.00 600.00
9 Opadry Pink 18.00 18.00 18.00 18.00
Coated tablet weight 618.00 618.00 618.00 618.00
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Manufacturing process for Example 1: Dry Granulation
1. Sift canagliflozin (having particle size of D90 around 5 micron to 40
micron) and intra granular excipients through suitable mesh.
2. Compact the blend into granules using roller compactor and mill through
suitable screen.
3. Blend extra granular excipients to the granules to ensure homogeneity of
components.
4. Lubricate the granules with magnesium stearate (sifted through #60
mesh) for 5 min.
5. Compress the blend using suitable tooling with the optimal physical
parameters under suitable manufacturing and RH controls.
6. Film coat the tablets with the opadry coating material to get a desired
coating weight of 3.0-4.0% w/w.
Note: Being a BCS class IV moiety, surfactant such as sodium lauryl sulfate,
polaxomer, cremophors, tweens and the like can also be incorporated.
Manufacturing process for Example 2: Hot melt granulation
1. Sift canagliflozin (having particle size of D90 around 5 micron to 40
micron) and intra granular excipients through suitable mesh.
2. Blend the above mixture to ensure homogeneity and granulate using
twin screw extrusion with use of chiller if required.
3. Blend the granules with the extra granular excipients to attain
homogeneity.
4. Lubricate above blend with magnesium stearate.
5. Compress the blend using suitable tooling with the optimal physical
parameters under suitable manufacturing and RH controls.
6. Film coat the tablets with the opadry coating material to get a desired
coating weight of 3.0-4.0% w/w.
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Note: Being a BCS class IV moiety, surfactant such as sodium lauryl
sulfate, polaxomer, cremophors, tweens and the like can also be
incorporated.
Manufacturing process for Example 3: Spray granulation
1. Sift all the intra granular excipients through suitable sieve and optionally
along with the drug substance.
2. Binder preparation: Dissolve amorphous canagliflozin (having particle
size of D90 around 5 micron to 40 micron) in acetone followed by the
binder to get a clear solution, alternatively the amorphous canagliflozin
may be taken in the dry mix and binder solution alone may be used for
granulation.
3. Granulate the blend with fluid bed processor using the binder solution at
suitable bed temperature.
4. Mill the above blend if required and extra granular excipients were added
and blended to attain homogeneity.
5. Lubricate the above blend with magnesium stearate.
6. Compress the blend using suitable tooling with the optimal physical
parameters under suitable manufacturing and RH controls.
7. Film coat the tablets with the opadry coating material to get a desired
coating weight of 3.0-4.0% w/w.
Note: Being a BCS class IV moiety, surfactant such as sodium lauryl sulfate,
polaxomer, cremophors, tweens and the like can also be incorporated.
Manufacturing process for Example 4: Direct compression
1. Co-sift amorphous canagliflozin (having particle size of D90 around 5
micron to 40 micron) and surfactant using suitable mesh.
2. Sift all other intra granular excipients using suitable mesh and blend with
the above material
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3. Lubricate the above blend with magnesium stearate for desired period of
time.
4. Compress the blend using suitable tooling with the optimal physical
parameters under suitable manufacturing and RH controls.
5. Film coat the tablets with the opadry coating material to get a desired
coating weight of 3.0-4.0% w/w.
Note: Surfactant can also be eliminated from above composition.
Example 5: Bi-layer tablet
S.NO Name of the Ingredient mg/ tab
First Layer
1 Canagliflozin API 300.00
2 Microcrystalline cellulose / Mannitol/ Lactose/calcium
phosphate etc.
149.56
3 Colloidal silicon dioxide/ Syloid/talc etc. 3.00
4 Colloidal silicon dioxide/ Syloid/talc etc. 45.00
5 Sodium starch glycolate/ Croscarmellose sodium/
Crospovidone etc.
30.00
6 Sodium lauryl sulphate / Polaxamer /Polyethylene
glycol etc
18.00
7 Magnesium stearate 2.22
Second Layer
8 Microcrystalline cellulose/ Mannitol 107.00
9 Sodium starch glycolate/ Croscarmellose sodium/
Crospovidone etc.
10.00
10 Sodium lauryl sulfate/ Polaxamer / Poly ethylene glycol
etc.
30.00
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11 Hydroxypropyl cellulose / Hydroxypropyl methyl
cellulose etc.
3.00
12 Magnesium stearate 2.22
Uncoated tablet weight 700.00
13 Opadry Pink 21.00
Coated tablet weight 721.00
Brief manufacturing process
1. Sift amorphous canagliflozin (having particle size of D90 around 5 micron
to 40 micron) and all other excipients of first layer using suitable mesh
2. Binder preparation: Dissolve hydroxypropyl cellulose in purified water
3. Granulate the blend using binder solution
4. Sift all the excipients of the second layer using suitable mesh and
granulate with the binder solution.
5. Lubricate the above blend with magnesium stearate for desired period of
time.
6. Compress bi-layer tablets using step 3 and step 5 suitable tooling with
the optimal physical parameters under suitable manufacturing and RH
controls.
7. Film coat the tablets with the opadry coating material to get a desired
coating weight of 3.0-4.0% w/w.
Note: Surfactant can also be eliminated from above composition ,CLAIMS:Claims:
1. A pharmaceutical formulation comprising amorphous canagliflozin.
2. The pharmaceutical formulation as claimed in claim 1, wherein the
formulation is prepared by dry granulation process.
3. The pharmaceutical formulation as claimed in claim 1, wherein the
formulation is prepared by hot melt extrusion process.
4. The pharmaceutical formulation as claimed in claim 1, wherein the
formulation is prepared by wet granulation process.
5. The pharmaceutical formulation as claimed in claim 1, wherein the
formulation is prepared by direct compression process.
6. The pharmaceutical formulation as claimed in claim 1-6, wherein the
formulation comprising one or more surfactant.
7. A pharmaceutical bi-layer formulation comprising amorphous
canagliflozin.
8. The pharmaceutical formulation as claimed in claim 7, wherein the
formulation comprising one or more surfactant.
9. The pharmaceutical formulation as claimed in any of the claims
comprising one or more pharmaceutically acceptable excipient selected
from the group consisting of diluents, binders, disintegrants, lubricants
and glidants.