The present invention relates to a pharmaceutical composition comprising
bempedoic acid or pharmaceutically acceptable salt thereof and optionally one or
more pharmaceuically acceptable excipient. The present invention further
provides a process for preparing such compositions and their use thereof to treat
cardiovascular diseases.
BACKGROUND OF THE INVENTION
Bempedoic acid is described chemically as: 8-hydroxy-2,2,14,14tetramethylpentadecanedioic acid.
Bempedoic acid is an adenosine triphosphate-citrate lyase (ACL) inhibitor.
Bempedoic acid is currently being marketed in United States under the brand
name NEXLETOL® as 180 mg tablet. It is indicated as an adjunct to diet and
maximally tolerated statin therapy for the treatment of adults with heterozygous
familial hypercholesterolemia or established atherosclerotic cardiovascular
disease who require additional lowering of LDL-C.
U.S. Patent No. 7,335,799 B2 discloses bempedoic acid or a salt, hydrate or
solvate thereof.
3
U.S. Patent No. 8,497,301 B2 relates to a method of lowering LDL levels by
administering bempedoic acid or salt thereof.
U.S. Patent No. 9,000,041 B2 relates to a method for treating a cardiovascular
disease, dyslipidemia by administering bempedoic acid.
U.S. Patent No. 9,624,152 B2 covers a method of inhibiting sterol synthesis in a
patient, comprising administering to a patient bempedoic acid.
U.S. Patent No. 10,118,881 B2 relates to a method for treating
hypercholesterolemia by administering bempedoic acid.
Indian Patent Publication No. IN 201917053385 discloses a granulated
composition comprising bempedoic acid admixed with a lubricant selected from
sodium stearyl fumarate, colloidal silicon dioxide and magnesium stearate, which
reduces or eliminates the stickiness problem.
Therefore, there exists a need in the art to develop an alternate pharmaceutical
composition of bempedoic acid which overcomes the problems associated with
prior art like stickiness and decreased flowability associated with bempedoic acid.
SUMMARY OF THE INVENTION
According to one aspect, there is provided a pharmaceutical composition
comprising bempedoic acid or pharmaceutically acceptable salt thereof and
optionally one or more pharmaceutically acceptable excipient.
According to another aspect, there is provided a pharmaceutical composition
comprising:
4
a) intragranular portion comprising bempedoic acid or pharmaceutically
acceptable salt thereof and optionally one or more pharmaceutically acceptable
excipient; and
b) extragranular portion comprising one or more pharmaceutically acceptable
excipient, wherein the intragranular portion is free of lubricant.
According to another aspect, there is provided a pharmaceutical composition
comprising:
a) intragranular portion comprising bempedoic acid or pharmaceutically
acceptable salt thereof and optionally one or more pharmaceutically acceptable
excipient; and
b) extragranular portion comprising one or more pharmaceutically acceptable
excipient, wherein the composition is free of colloidal silicon dioxide, sodium
stearyl fumarate, and magnesium stearate.
According to another aspect, there is provided a process for preparing a
pharmaceutical composition comprising bempedoic acid or pharmaceutically
acceptable salt thereof, wherein the process comprising the steps of:
a) blending bempedoic acid and optionally one or more pharmaceutically
acceptable excipient;
b) compacting the blend using roller compaction to form granules to form
intragranular portion;
c) blending the granules with one or more pharmaceutically acceptable excipient
to form extragranular portion; and
d) compressing the granules into tablet;
wherein the intragranular portion is free of lubricant.
According to another aspect, there is provided a process for preparing a
pharmaceutical composition comprising bempedoic acid or pharmaceutically
acceptable salt thereof, wherein the process comprising the steps of:
5
a) blending bempedoic acid and optionally one or more pharmaceutically
acceptable excipient;
b) compacting the blend using roller compaction to form granules to form
intragranular portion;
c) blending the granules with one or more pharmaceutically acceptable excipient
to form extragranular portion; and
d) compressing the granules into tablet;
wherein the composition is free of colloidal silicon dioxide, sodium stearyl
fumarate, and magnesium stearate.
According to another aspect, there is provided a process for preparing a
pharmaceutical composition comprising bempedoic acid or pharmaceutically
acceptable salt thereof, wherein the process comprising the steps of:
a) blending bempedoic acid and optionally one or more pharmaceutically
acceptable excipient;
b) preparing the binder solution using suitable solvent;
c) granulating the blend of step a) using binder solution of step b) to form
granules to form intragranular portion;
d) blending the granules of step c) with one or more pharmaceutically acceptable
excipient to form extragranular portion;
e) compressing the granules into tablet;
wherein the intragranular portion is free of lubricant.
According to another aspect, there is provided a process for preparing a
pharmaceutical composition comprising bempedoic acid or pharmaceutically
acceptable salt thereof, wherein the process comprising the steps of:
a) blending bempedoic acid and optionally one or more pharmaceutically
acceptable excipient;
b) preparing the binder solution using suitable solvent;
c) granulating the blend of step a) using binder solution of step b) to form
granules to form intragranular portion;
6
d) blending the granules of step c) with one or more pharmaceutically acceptable
excipient to form extragranular portion;
e) compressing the granules into tablet;
wherein the composition is free of colloidal silicon dioxide, sodium stearyl
fumarate, and magnesium stearate.
According to one embodiment, the solvent for granulation is aqueous or nonaqueous.
According to another aspect, there is provided a process for preparing a
pharmaceutical composition comprising bempedoic acid or pharmaceutically
acceptable salt thereof, wherein the process comprising the steps of:
a) blending bempedoic acid and one or more pharmaceutically acceptable
excipient to form powder blend;
b) compressing the powder blend of step a) into tablet;
wherein the composition is free of colloidal silicon dioxide, sodium stearyl
fumarate, and magnesium stearate.
According to one embodiment, the bempedoic acid is present in crystalline form
or amorphous form.
According to another aspect, the present invention is useful for treating
cardiovascular diseases.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a pharmaceutical composition comprising
bempedoic acid or pharmaceutically acceptable salt thereof and one or more
pharmaceutically acceptable excipient.
There is provided a pharmaceutical composition comprising:
7
a) intragranular portion comprising bempedoic acid or pharmaceutically
acceptable salt thereof and optionally one or more pharmaceutically acceptable
excipient; and
b) extragranular portion comprising one or more pharmaceutically acceptable
excipient, wherein the intragranular portion is free of lubricant.
The present invention provides a pharmaceutical composition comprising:
a) intragranular portion comprising bempedoic acid or pharmaceutically
acceptable salt thereof and optionally one or more pharmaceutically acceptable
excipient; and
b) extragranular portion comprising one or more pharmaceutically acceptable
excipient, wherein the composition is free of colloidal silicon dioxide, sodium
stearyl fumarate, and magnesium stearate.
The pharmaceutical compositions can be prepared by using any suitable method
known in the art such as direct compression, dry or wet granulation (aqueous/nonaqueous or combination), extrusion spheronization, melt extrusion, melt
granulation, coating over inert spheres, spray coating, spray drying and solvent
evaporation.
The present invention provides a process for preparing a pharmaceutical
composition comprising bempedoic acid or pharmaceutically acceptable salt
thereof, wherein the process comprising the steps of:
a) blending bempedoic acid and optionally one or more pharmaceutically
acceptable excipient;
b) compacting the blend using roller compaction to form granules to form
intragranular portion;
c) blending the granules with one or more pharmaceutically acceptable excipient
to form extragranular portion; and
d) compressing the granules into tablet;
wherein the intragranular portion is free of lubricant.
8
The present invention provides a process for preparing a pharmaceutical
composition comprising bempedoic acid or pharmaceutically acceptable salt
thereof, wherein the process comprising the steps of:
a) blending bempedoic acid and optionally one or more pharmaceutically
acceptable excipient;
b) compacting the blend using roller compaction to form granules to form
intragranular portion;
c) blending the granules with one or more pharmaceutically acceptable excipient
to form extragranular portion; and
d) compressing the granules into tablet;
wherein the composition is free of colloidal silicon dioxide, sodium stearyl
fumarate, and magnesium stearate.
The present invention provides a process for preparing a pharmaceutical
composition comprising bempedoic acid or pharmaceutically acceptable salt
thereof, wherein the process comprising the steps of:
a) blending bempedoic acid and optionally one or more pharmaceutically
acceptable excipient;
b) preparing the binder solution using suitable solvent;
c) granulating the blend of step a) using binder solution of step b) to form
granules to form intragranular portion;
d) blending the granules of step c) with one or more pharmaceutically acceptable
excipient to form extragranular portion;
e) compressing the granules into tablet;
wherein the intragranular portion is free of lubricant.
The present invention provides a process for preparing a pharmaceutical
composition comprising bempedoic acid or pharmaceutically acceptable salt
thereof, wherein the process comprising the steps of:
a) blending bempedoic acid and optionally one or more pharmaceutically
acceptable excipient;
9
b) preparing the binder solution using suitable solvent;
c) granulating the blend of step a) using binder solution of step b) to form
granules to form intragranular portion;
d) blending the granules of step c) with one or more pharmaceutically acceptable
excipient to form extragranular portion;
e) compressing the granules into tablet;
wherein the composition is free of colloidal silicon dioxide, sodium stearyl
fumarate, and magnesium stearate.
The solvent used for wet granulation is aqueous or non-aqueous.
The present invention provides a process for preparing a pharmaceutical
composition comprising bempedoic acid or pharmaceutically acceptable salt
thereof, wherein the process comprising the steps of:
a) blending bempedoic acid and one or more pharmaceutically acceptable
excipient to form powder blend;
b) compressing the powder blend of step a) into tablet;
wherein the composition is free of colloidal silicon dioxide, sodium stearyl
fumarate, and magnesium stearate.
The term “bempedoic acid” used herein refers to a pharmaceutically active
molecule as well as its pharmaceutically acceptable salts, esters, amides, prodrugs,
metabolites, enantiomers, polymorphs, analogues, etc. that induce a desired
pharmacological or physiological effect. The term also includes all polymorphic
forms, whether crystalline or amorphous.
The pharmaceutical composition contains bempedoic acid in crystalline form,
amorphous form or mixtures thereof.
10
The pharmaceutical composition comprises about 5 mg to about 500 mg of
bempedoic acid or pharmaceutically acceptable salts, ester, solvates, polymorphs
thereof.
The pharmaceutical composition contains bempedoic acid having particle size of
D90 less than 200µ (microns).
The pharmaceutically acceptable excipients are selected from the group
comprising diluents/fillers, binders, disintegrants, glidants, lubricants,
solubilizers/surfactants/wetting agents, plasticizers, solvents and the like.
Suitable diluents/fillers include, but are not limited to starch, pregelatinized
starch, powdered celluloses, polysaccharides, dibasic calcium phosphate, calcium
phosphate, calcium carbonate, calcium citrate, tricalcium citrate, magnesium
carbonate, lactose monohydrate, lactose anhydrous, microcrystalline cellulose,
mannitol, dextrose, dextrin, maltodextrin, sucrose, sorbitol, xylitol, lactitol.
inositol, dextrates, lactitol, maltodextrin, trehalose, and/or combinations thereof.
Further, the amount of diluent is preferably in the range of 10% w/w to 90% w/w
by weight of the composition.
Suitable binders include, but are not limited to acacia, alginic acid, agar, calcium
carrageenan, dextrin, gelatin, liquid glucose, gum, cellulose derivatives such as
hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcellulose,
microcrystalline cellulose, sodium carboxymethylcellulose, ethylcellulose, pectin,
polyethylene glycol, povidone, starch, pregelatinized starch and/or combinations
thereof. Further, the amount of binder is preferably in the range of 0.5% w/w to
50% w/w by weight of the composition.
Suitable disintegrants include, but are not limited to sodium starch glycolate,
croscarmellose sodium, crosslinked polyvinylpyrrolidone, calcium and sodium
carboxymethylcellulose, pregelatinized starch, magnesium trisilicate, corn starch,
11
potato starch and/or combinations thereof. Further, the amount of disintegrant is
preferably in the range of 1% w/w to 25% w/w by weight of the composition.
Suitable lubricants/glidants may comprise but not limited to magnesium stearate,
colloidal silicon dioxide, aluminum silicate, sodium stearyl fumarate, talc, stearic
acid, calcium stearate, zinc stearate, talc, waxes, boric acid, hydrogenated
vegetable oil, sodium chlorate, magnesium lauryl sulfate, starch, sodium lauryl
sulfate, sodium oleate, sodium acetate, sodium benzoate, polyethylene glycol,
fatty acid, fumaric acid, glyseryl palmito sulphate and/or combinations thereof.
Further, the amount of lubricant is preferably in the range of 0.01% w/w to 20%
w/w by weight of the composition.
Suitable solubilizers/surfactants include but are not limited to poloxamer,
polysorbate, cremophore, soluplus, lecithin, sodium lauryl sulfate, polyethylene
glycol and/or combinations thereof.
Suitable solvents include but are not limited to purified water, methanol, ethanol,
isopropyl alcohol, methylene chloride/ dichloromethane, chloroform, ethylacetate,
acetone and/or mixtures thereof.
Suitable plasticizers include but are not limited to, dibutyl sebacate; vegetable oil,
e.g., castor oil or glycerol/glycerin; or a glyceryl ester of a fatty acid, e.g., glyceryl
triacetate or glyceryl monoricinoleate, polyethylene glycol, triethyl citrate, talc
and/or mixtures thereof.
The pharmaceutical composition may be in the form of tablets, capsules, tablets
filled in capsule, mini tablets filled in capsule, sachets containing powder or
granules, pellets, and the like.
The pharmaceutical composition is meant for once daily or twice daily
administration.
12
The pharmaceutical composition is an oral dosage form.
According to one embodiment, the pharmaceutical composition comprises a solid
dispersion of bemepedoic acid in one or more carrier and optionally including
other pharmaceutically acceptable excipients. The solid dispersion may optionally
be encapsulated in hard gelatin capsules, compressed into a tablet, or may be
granulated with a pharmaceutically acceptable excipients. The carrier can be
hydrophilic or hydrophobic or water swellable, which include but not limited to
polyethylene glycol (PEG), phospholipids, polyvinylpyrrolidone, cellulose
derivatives such as methyl cellulose, carboxymethyl cellulose, hydroxypropyl
cellulose, hydroxypropyl methyl cellulose, ethylcellulose, poly (ethylene oxide),
carboxyvinyl polymer, carboxymethylethylcellulose, polyvinylalcohol and
polyvinylacetate (PVA)/PVP copolymer, guar gum, xanthan gum, sodium
alginate, dextrin, cyclodextrin, crospovidone, polyacrylates polymethacrylates,
urea, soluplus, sugar, polyols and their polymers, surfactants such as poloxamer,
tween, gelucire and/or combinations thereof.
The pharmaceutical compositions of the present invention may be film coated
with various film coating materials known in the art e.g. commercially available
Opadry®. The coating may contain film-forming agents, pigments/opacifier such
as iron oxide, titanium dioxide, zinc oxide, a plasticizer and one or more other
pharmaceutically acceptable excipients.
Examples of film-forming agents include polyvinyl alcohol, ethylcellulose,
hydroxypropyl methylcellulose, hydroxypropylcellulose, methylcellulose,
carboxymethyl cellulose, hydroxymethylcellulose, hydroxyethylcellulose,
cellulose acetate, hydroxypropyl methylcellulose phthalate, cellulose acetate
phthalate, cellulose acetate trimellitate; waxes such as polyethylene glycol;
methacrylic acid polymers such as Eudragit®. Alternatively, commercially
available coating compositions comprising film-forming polymers marketed
under various trade names, such as Opadry® may also be used.
13
According to one embodiment, the pharmaceutical compositions of the present
invention can be in the form of modified release dosage form which include, but
not limited to, controlled release, sustained release, extended release, prolonged
release dosage form. Various rate controlling agents/techniques known in the art
may be used to control the release of the drug from the dosage form.
Suitable release controlling agents, include but are not limited to, cellulose
derivatives such as hydroxypropylmethylcellulose, hydroxypropylcellulose,
hydroxyethylcellulose, ethylcellulose, microcrystalline cellulose, methylcellulose,
carboxymethylcellulose, alginate, poly(alkylcyanoacrylate), polyethylene,
poly(ethylene-co-vinylacetate), poly(hydroxyethyl methacrylate),
poly(hydroxypropylethyl methacrylate), poly(methyl methacrylate), polyurethane,
poly(vinyl alcohol), polyvinyl acetate, poly(acrylic acid), polyvinylpyrrolidone,
poly(ethylene oxide), poloxamers, polymethacrylates, gums, waxes, collagen,
silicon and/or combinations thereof.
The pharmaceutical compositions can be in the form of matrix or reservoir and/or
combinations thereof.
The pharmaceutical compositions are useful for treating cardiovascular diseases
which refer to diseases of the heart and circulatory system. These diseases are
often associated with dyslipoproteinemias and/or dyslipidemias. Cardiovascular
diseases which the compositions of the present invention are useful for preventing
or treating include but are not limited to arteriosclerosis; atherosclerosis; stroke;
ischemia; endothelium dysfunctions, in particular those dysfunctions affecting
blood vessel elasticity; peripheral vascular disease; coronary heart disease;
myocardial infarction; cerebral infarction and restenosis.
The composition can be administered alone or in combination with one or more
other lipid lowering drugs, either simultaneously or sequentially or in fixed dose
combination. The other lipid lowering drugs, include, but are not limited
hydroxymethylglutaryl (HMG) CoA reductase inhibitors such as statins e.g.
14
atorvastatin, rosuvastatin, simvastatin, lovastatin, pravastatin, fluvastatin, or
pitavastatin; cholesterol absorbing inhibitors such as ezetimibe; fibric acid
derivatives such as fenofibrate, gemfibrozil, clofibrate, bezafibrat, ciprofibrate;
bile acid sequestrants such as cholestyramine, colestipol, colesevelam; nicotinic
acid; PCKS9 inhibitor such as evolocumab, alirocumab; omega 3 fatty acids
and/or combinations thereof.
The various embodiments of the present invention can be assembled in several
different ways.
The following examples will illustrate in more detail the various aspects of the
present invention.
EXAMPLE 1:
Ingredient Qty./Tablet
(mg)
Bempedoic acid 180.000
Lactose monohydrate 30.000
Microcrystalline cellulose 48.000
Hydroxypropyl cellulose 12.000
Purified water q.s.
Sodium starch glycolate 15.000
Colloidal silicon dioxide 3.000
Talc 12.000
Uncoated Tablet Weight 300.000
Film Coating
Opadry 9.000
Purified Water q.s.
Total Weight 309.000
Brief Manufacturing process
1. Sifting all the ingredients through appropriate sieves.
2. Dry mixing pre-sifted bempedoic acid, lactose monohydrate and
microcrystalline cellulose.
15
3. Adding hydroxylpropyl cellulose to water and keep stirring till uniform
dispersion is obtained.
4. Granulating the dry mix of step 2 using dispersion of step 3 to obtain granules.
5. Drying the granules followed by passing through appropriate sieve and then
passing through multi mill.
6. Blending the granules of step 5 with sodium starch glycolate, colloidal silicon
dioxide and talc.
7. Compressing the blend of step 6 into tablets using suitable tools.
8. Then film coating the compressed tablets using a coating machine.
Example 2:
Ingredient Qty./Tablet
(mg)
Bempedoic acid 180.000
Lactose monohydrate 30.000
Microcrystalline cellulose 46.000
Hydroxypropyl cellulose 12.000
Polyethylene glycol 2.000
Purified water q.s.
Sodium starch glycolate 15.000
Colloidal silicon dioxide 3.000
Talc 12.000
Uncoated Tablet Weight 300.000
Film Coating
Opadry 9.000
Purified Water q.s.
Total weight 309.000
Brief Manufacturing process
1. Sifting all the ingredients through appropriate sieves.
2. Dry mixing bempedoic acid, lactose monohydrate and microcrystalline
cellulose.
3. Adding polyethylene glycol to water and then adding hydroxylpropyl
cellulose to it and keep stirring till uniform dispersion is obtained.
4. Granulating the dry mix of step 2 using dispersion of step 3 to form granules.
16
5. Drying the granules, followed by sieving and milling.
6. Blending the granules with sodium starch glycolate, colloidal silicon dioxide
and talc
7. Compressing the blend of step 6 into tablets using suitable tools.
8. Film coating the compressed tablets.
Example 3:
Brief Manufacturing process
1. Sifting all the ingredients through appropriate sieves.
2. Dry mixing bempedoic acid, lactose monohydrate and microcrystalline
cellulose.
3. Adding hydroxylpropyl cellulose to water and keep stirring till uniform
dispersion is obtained.
4. Granulating the dry mix of step 2 using dispersion of step 3.
5. Drying the granules, followed by sifting and milling.
6. Mixing the milled granules with sodium starch glycolate and colloidal silicon
dioxide.
Ingredient Qty./Tablet
(mg)
Bempedoic acid 180.000
Lactose monohydrate 30.000
Microcrystalline cellulose 57.000
Hydroxypropyl cellulose 12.000
Purified water q.s.
Sodium starch glycolate 15.000
Colloidal silicon dioxide 3.000
Magnesium stearate / Calcium stearate / Stearic
acid / Sodium stearyl fumarate 3.000
Uncoated Tablet Weight 300.000
Film Coating
Opadry 9.000
Purified Water q.s.
Total weight 309.000
17
7. Mixing the pre-lubricated blend of step 6 with magnesium stearate / calcium
stearate / stearic acid / sodium stearyl fumarate in a blender.
8. Compressing the blend of step 7 into tablets using suitable tools and then film
coating the tablets.
Example 4:
Ingredient Qty./Tablet
(mg)
Bempedoic acid 180.000
Lactose monohydrate 30.000
Microcrystalline cellulose 60.000
Hydroxypropyl cellulose 15.000
Purified Water q.s.
Sodium starch glycolate 9.000
Talc / Calcium stearate / Stearic
acid 6.000
Uncoated Tablet Weight 300.000
Film Coating
Opadry 9.000
Purified Water q.s.
Total weight 309.000
Brief Manufacturing process
1. Sifting all the ingredients through appropriate sieves.
2. Mixing pre-sifted bempedoic acid, lactose monohydrate and microcrystalline
cellulose.
3. Adding hydroxypropyl cellulose to purified water and keep stirring till a clear
solution is obtained.
4. Adding binder of step 3 to dry mix of step 2 to obtain granules
5. Drying the granules and then sifting and milling the granules.
6. Mixing the sifted granules with sodium starch glycolate and or talc / calcium
stearate / stearic acid.
7. Compress the blend of step 6 into tablets using suitable tools.
8. Film coating the tablets of step 7 using Opadry.
18
Example 5:
Ingredient Qty./Tablet
(mg)
Bempedoic acid 180.000
Lactose monohydrate 30.000
Microcrystalline cellulose 60.000
Sodium starch glycolate 9.000
Povidone / Hydroxypropyl cellulose 15.000
Talc / Calcium stearate / Stearic acid 3.000
Talc / Calcium stearate / Stearic acid 3.000
Uncoated Tablet Weight 300.000
Film Coating
Opadry 9.000
Purified Water q.s.
Total weight 309.000
Brief Manufacturing process
1. Sifting all the ingredients through appropriate sieves.
2. Adding pre-sifted bempedoic acid, lactose monohydrate, microcrystalline
cellulose, sodium starch glycolate, povidone or hydroxypropyl cellulose, talc
or calcium stearate or stearic acid in a blender and mix for suitable time.
3. Compacting the blended material of step 2 into flakes/ribbons using a suitable
compactor and obtain granules of uniform size by sizing.
4. Mixing the sifted granules with talc or calcium stearate or stearic acid in a
blender.
5. Compressing the blend of step 4 into tablets using suitable tools.
6. Then film coating the compressed tablets using Opadry.
Example 6:
Ingredient Qty./Tablet
(mg)
Bempedoic acid 180.000
Lactose monohydrate 30.000
Microcrystalline cellulose 60.000
Povidone 15.000
Isopropyl alcohol q.s.
19
Sodium starch glycolate 9.000
Talc / Calcium stearate / Stearic acid 6.000
Uncoated Tablet Weight 300.000
Film Coating
Opadry 9.000
Purified Water q.s.
Total weight 309.000
Brief Manufacturing process
1. Sifting all the ingredients through appropriate sieves.
2. Mixing pre-sifted bempedoic acid, lactose monohydrate and microcrystalline
cellulose.
3. Adding povidone to Isopropyl alcohol and keep stirring till a clear solution is
obtained for use as binder.
4. Adding binder of step 3 to dry mix of step 2 to obtain granules.
5. Drying the granules followed by sifting and milling.
6. Mixing the sifted granules with sodium starch glycolate and talc or calcium
stearate or stearic acid in a blender.
7. Compressing the blend of step 6 into tablets using suitable tools.
8. Film coating the compressed tablets using a suitable coating

We Claim:
1. A pharmaceutical composition comprising:
a) intragranular portion comprising bempedoic acid or pharmaceutically
acceptable salt thereof and optionally one or more pharmaceutically
acceptable excipient; and
b) extragranular portion comprising one or more pharmaceutically acceptable
excipient, wherein the intragranular portion is free of lubricant.
2. A pharmaceutical composition comprising:
a) intragranular portion comprising bempedoic acid or pharmaceutically
acceptable salt thereof and optionally one or more pharmaceutically
acceptable excipient; and
b) extragranular portion comprising one or more pharmaceutically acceptable
excipient, wherein the composition is free of colloidal silicon dioxide,
sodium stearyl fumarate, and magnesium stearate.
3. A process for preparing a pharmaceutical composition comprising bempedoic
acid or pharmaceutically acceptable salt thereof, wherein the process
comprising the steps of:
a) blending bempedoic acid and optionally one or more pharmaceutically
acceptable excipient;
b) compacting the blend using roller compaction to form granules to form
intragranular portion;
c) blending the granules with one or more pharmaceutically acceptable
excipient to form extragranular portion; and
d) compressing the granules into tablet;
wherein the intragranular portion is free of lubricant.
21
4. A process for preparing a pharmaceutical composition comprising bempedoic
acid or pharmaceutically acceptable salt thereof, wherein the process
comprising the steps of:
a) blending bempedoic acid and optionally one or more pharmaceutically
acceptable excipient;
b) compacting the blend using roller compaction to form granules to form
intragranular portion;
c) blending the granules with one or more pharmaceutically acceptable
excipient to form extragranular portion; and
d) compressing the granules into tablet;
wherein the composition is free of colloidal silicon dioxide, sodium stearyl
fumarate, and magnesium stearate.
5. A process for preparing a pharmaceutical composition comprising bempedoic
acid or pharmaceutically acceptable salt thereof, wherein the process
comprising the steps of:
a) blending bempedoic acid and optionally one or more pharmaceutically
acceptable excipient;
b) preparing the binder solution using suitable solvent;
c) granulating the blend of step a) using binder solution of step b) to form
granules to form intragranular portion;
d) blending the granules of step c) with one or more pharmaceutically
acceptable excipient to form extragranular portion;
e) compressing the granules into tablet;
wherein the intragranular portion is free of lubricant.
6. A process for preparing a pharmaceutical composition comprising bempedoic
acid or pharmaceutically acceptable salt thereof, wherein the process
comprising the steps of:
a) blending bempedoic acid and optionally one or more pharmaceutically
acceptable excipient;
22
b) preparing the binder solution using suitable solvent;
c) granulating the blend of step a) using binder solution of step b) to form
granules to form intragranular portion;
d) blending the granules of step c) with one or more pharmaceutically
acceptable excipient to form extragranular portion;
e) compressing the granules into tablet;
wherein the composition is free of colloidal silicon dioxide, sodium stearyl
fumarate, and magnesium stearate.
7. The process as claimed in claim 5 or 6, wherein the solvent is aqueous or nonaqueous.
8. A process for preparing a pharmaceutical composition comprising bempedoic
acid or pharmaceutically acceptable salt thereof, wherein the process
comprising the steps of:
a) blending bempedoic acid and one or more pharmaceutically acceptable
excipient to form powder blend;
b) compressing the powder blend of step a) into tablet;
wherein the composition is free of colloidal silicon dioxide, sodium stearyl
fumarate, and magnesium stearate.