FIELD OF THE INVENTION
[0001] The present disclosure generally relates to the field of pharmaceuticals. Particularly, it relates to pharmaceutical compositions comprising bempedoic acid, clopidogrel and aspirin. More particularly, it relates to pharmaceutical formulation and process of preparing the same, said pharmaceutical formulation comprising bempedoic acid, clopidogrel and aspirin in discrete units; and wherein bempedoic acid and clopidogrel are in immediate release form, and aspirin is in enteric coated form.
BACKGROUND OF THE INVENTION
[0002] Background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the present invention, or that any publication specifically or implicitly referenced is prior art. [0003] Dyslipidemia is a term used for abnormal levels of fat or lipid in the blood. The fat or lipid components of the blood may be either high or low to be categorized as dyslipidemia. Common plasma lipids include cholesterol, triglycerides, plasma lipoproteins and cholesterol esters. A diet rich in lipids or fats, obesity, genetics, sedentary lifestyle, or age can all be causes for such a condition. The symptomatic indications of the condition are faint and fairly difficult to read. However, it is responsible for a number of co-morbidities which show symptoms. Atherosclerotic arterial disease or hardening of arteries is a common condition resulting from fat buildup and deposition in the walls of arteries blocking the flow of blood. It can lead to higher blood pressure, or ischemic stroke.
[0004] Statins such as Atorvastatin, or Lovastatin are some of the common medicaments administered for dyslipidemia. However, there is a continuing need in the art to look for improved pharmaceutical compositions for management of dyslipidemia.

OBJECT OF THE INVENTION
[0005] An object of the present disclosure is to provide a pharmaceutical
composition comprising bempedoic acid, clopidogrel and aspirin.
[0006] Another object of the present disclosure is to provide a pharmaceutical
formulation comprising bempedoic acid, clopidogrel and aspirin in discrete units.
[0007] Yet another object of the present disclosure is to provide a pharmaceutical
formulation comprising of bempedoic acid, clopidogrel and aspirin in discrete
units; and wherein bempedoic acid and clopidogrel are in immediate release form,
and aspirin is in enteric coated form.
[0008] In still another object of the present disclosure is to provide a
pharmaceutical formulation comprising of bempedoic acid, clopidogrel and
aspirin in discrete units; and wherein the formulation is a fixed dose formulation.
SUMMARY OF THE INVENTION
[0009] This summary is provided to introduce a selection of concepts in a
simplified form that are further described below in Detailed Description section.
This summary is not intended to identify key features or essential features of the
subject matter, nor is it intended to be used as an aid in determining the scope of
the subject matter.
[0010] In an aspect, the present disclosure provides a pharmaceutical composition
comprising bempedoic acid, clopidogrel and aspirin.
[0011] In an embodiment, the composition comprises bempedoic acid in an
amount ranging from about 10% w/w to about 40% w/w with respect to the
composition.
[0012] In an embodiment, the composition comprises clopidogrel in an amount
ranging from about 10% w/w to about 30% w/w with respect to the composition.
[0013] In an embodiment, the composition comprises aspirin in an amount
ranging from about 10% w/w to about 30% w/w with respect to the composition.
[0014] In an aspect, the present disclosure provides a pharmaceutical formulation
comprising bempedoic acid, clopidogrel, aspirin and one or more
pharmaceutically acceptable excipient(s).

[0015] In an embodiment, the present disclosure provides a pharmaceutical formulation comprising bempedoic acid, clopidogrel, aspirin, and one or more pharmaceutically acceptable excipient(s); wherein bempedoic acid, clopidogrel and aspirin are in discrete units; and wherein bempedoic acid and clopidogrel are in immediate release form, and aspirin is in enteric coated form. [0016] In an embodiment, the formulation comprises bempedoic acid in an amount ranging from about 10% w/w to about 35% w/w with respect to the formulation. In an embodiment, the formulation comprises clopidogrel in an amount ranging from about 10% w/w to about 15% w/w with respect to the formulation. In an embodiment, the formulation comprises aspirin in an amount ranging from about 10% w/w to about 15% w/w with respect to the formulation. [0017] In an embodiment, the excipient may be selected from fillers, binders, lubricants, glidants, swelling agents, sustained-release agents, coating agents, coloring agent, flavoring agent, diluents, disintegrating agents, pH modifiers, solvent, carrier or combinations thereof.
[0018] In an embodiment, the formulation may be present in the form of a solid dosage form for oral administration. Specifically, the formulation may be a tablet formulation, granule formulation, capsule formulation or pellet formulation. [0019] In an embodiment, bempedoic acid may be present in an immediate release form of tablets, pellets or granules. In a specific embodiment, bempedoic acid is present as one or more immediate release tablet(s). In another specific embodiment, bempedoic acid is present as immediate release granules. [0020] In a specific embodiment, clopidogrel may be present as immediate release tablets, pellets or granules. In a specific embodiment, the formulation may comprise one or more immediate release tablet(s) comprising clopidogrel. [0021] In a specific embodiment, aspirin may be present as an enteric coated tablet or pellet. In a specific embodiment, the formulation may comprise one or more enteric coated tablet(s) comprising aspirin.
[0022] In one embodiment, the present disclosure provides a pharmaceutical formulation comprising bempedoic acid, clopidogrel, aspirin, and one or more pharmaceutically acceptable excipient(s); wherein the formulation comprises one

or more immediate release tablet(s) of bempedoic acid, one or more immediate release tablet(s) of clopidogrel and one or more enteric coated tablet(s) of aspirin. In one embodiment, the formulation comprises one or more immediate release tablet(s) of bempedoic acid comprising about 60% w/w to about 70% w/w of bempedoic acid; one or more immediate release tablet(s) of clopidogrel comprising about 30% w/w to about 40% w/w of clopidogrel and one or more enteric coated tablet(s) of aspirin comprising about 40% w/w to about 50% w/w of aspirin.
[0023] In one embodiment, the present disclosure provides a pharmaceutical formulation comprising bempedoic acid, clopidogrel, aspirin, and one or more pharmaceutically acceptable excipient(s); wherein the formulation comprises immediate release granules of bempedoic acid, one or more immediate release tablet(s) of clopidogrel and one or more enteric coated tablet(s) of aspirin. In one embodiment, the formulation comprises immediate release granules of bempedoic acid comprising about 60% w/w to about 70% w/w of bempedoic acid; one or more immediate release tablet(s) of clopidogrel comprising about 60% w/w to about 70%) w/w of clopidogrel and one or more enteric coated tablet(s) of aspirin comprising about 50% w/w to about 60% w/w of aspirin.
[0024] In another aspect, the present disclosure provides a process for preparing a pharmaceutical formulation comprising bempedoic acid, clopidogrel, aspirin and one or more pharmaceutically acceptable excipient(s).
[0025] In an embodiment, the present disclosure provides a process for preparing a pharmaceutical formulation comprising the steps of: (a) preparing an immediate release tablet or granules of bempedoic acid; (b) preparing an immediate release tablet of clopidogrel; (c) preparing an enteric coating tablet of aspirin; and (d) adding the immediate release tablet or granules of bempedoic acid, immediate release tablet of clopidogrel and enteric coating tablet of aspirin in a capsule to give the pharmaceutical formulation.
[0026] Other aspects of the invention will be set forth in the description which follows, and in part will be apparent from the description, or may be learnt by the practice of the invention.

DETAILED DESCRIPTION
[0027] The following is a detailed description of embodiments of the disclosure. The embodiments are in such detail as to clearly communicate the disclosure. However, the amount of detail offered is not intended to limit the anticipated variations of embodiments; on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present disclosure.
[0028] All publications herein are incorporated by reference to the same extent as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. Where a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply. [0029] Reference throughout this specification to "one embodiment" or "an embodiment" means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.
[0030] In some embodiments, numbers have been used for quantifying weights, percentages, concentrations, and so forth, to describe certain embodiments of the invention and are to be understood as being modified in some instances by the term "about." Accordingly, in some embodiments, the numerical parameters set forth in the written description are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment. In some embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations,

the numerical values set forth in the specific examples are reported as precisely as
practicable. The numerical values presented in some embodiments of the
invention may contain certain errors necessarily resulting from the standard
deviation found in their respective testing measurements.
[0031] Various terms as used herein are shown below. To the extent a term used
is not defined below, it should be given the broadest definition persons in the
pertinent art have given that term as reflected in printed publications and issued
patents at the time of filing.
[0032] As used in the description herein, the meaning of "a," "an," and "the"
includes plural reference unless the context clearly dictates otherwise. Also, as
used in the description herein, the meaning of "in" includes "in" and "on" unless
the context clearly dictates otherwise.
[0033] Unless the context requires otherwise, throughout the specification which
follow, the word "comprise" and variations thereof, such as, "comprises" and
"comprising" are to be construed in an open, inclusive sense that is as "including,
but not limited to."
[0034] The recitation of ranges of values herein is merely intended to serve as a
shorthand method of referring individually to each separate value falling within
the range. Unless otherwise indicated herein, each individual value is incorporated
into the specification as if it were individually recited herein.
[0035] All methods described herein can be performed in any suitable order
unless otherwise indicated herein or otherwise clearly contradicted by context.
The use of any and all examples, or exemplary language (e.g., "such as") provided
with respect to certain embodiments herein is intended merely to better illuminate
the invention and does not pose a limitation on the scope of the invention. No
language in the specification should be construed as indicating any non-claimed
element essential to the practice of the invention.
[0036] Groupings of alternative elements or embodiments of the invention
disclosed herein are not to be construed as limitations. Each group member can be
referred to individually or in any combination with other members of the group or
other elements found herein. One or more members of a group can be included in,

or deleted from, a group for reasons of convenience and/or patentability. When
any such inclusion or deletion occurs, the specification is herein deemed to
contain the group as modified.
[0037] The description that follows, and the embodiments described therein, is
provided by way of illustration of an example, or examples, of particular
embodiments of the principles and aspects of the present disclosure. These
examples are provided for the purposes of explanation, and not of limitation, of
those principles and of the disclosure.
[0038] The headings and abstract of the invention provided herein are for
convenience only and do not interpret the scope or meaning of the embodiments.
[0039] The following discussion provides many example embodiments of the
inventive subject matter. Although each embodiment represents a single
combination of inventive elements, the inventive subject matter is considered to
include all possible combinations of the disclosed elements. Thus, if one
embodiment comprises elements A, B, and C, and a second embodiment
comprises elements B and D, then the inventive subject matter is also considered
to include other remaining combinations of A, B, C, or D, even if not explicitly
disclosed.
[0040] As described herein, the term 'active ingredient' has the meaning known in
the state of the art. The term denotes a pharmaceutical drug or compound that
produces a desired biological activity in the body.
[0041] The term, "pharmaceutically acceptable excipient" as used herein refers to
an excipient comprised of a material that is not biologically or otherwise
undesirable.
[0042] The term, "subject" as used herein refers to an animal, preferably a
mammal, and most preferably a human. The term "mammal" used herein refers to
warm-blooded vertebrate animals of the class 'mammalia', including humans,
characterized by a covering of hair on the skin and, in the female, milk-producing
mammary glands for nourishing the young, the term mammal includes animals
such as cat, dog, rabbit, bear, fox, wolf, monkey, deer, mouse, pig and human.

[0043] The term, 'management', or 'treatment' as used herein refers to alleviate,
slow the progression, attenuation, prophylaxis or as such treat the existing disease
or condition. Treatment also includes treating, preventing development of, or
alleviating to some extent, one or more of the symptoms of the diseases or
condition.
[0044] The term 'immediate release' as used herein refers to rapid dissolution of
the active ingredient in vitro or in vivo in the gastrointestinal tract. Preferably, it
means dissolution of at least 80% of the active ingredient within 30 minutes.
[0045] The present disclosure generally relates to a pharmaceutical composition
for dyslipidaemia and associated co-morbidities.
[0046] In an embodiment, the disclosure provides a fixed dose composition of
active ingredients for dyslipidaemia; wherein the active ingredients are bempedoic
acid, clopidogrel and aspirin. Each active ingredient exhibits desirable
bioavailability.
[0047] Aspects of the present disclosure provide a composition and formulation
for management of dyslipidemia.
[0048] Aspects of the present disclosure provide a composition and formulation
for management of dyslipidemia without statins. Bempedoic acid acts as a
compound with efficacy against dyslipidemia and has been employed as opposed
to conventional statins based formulations.
[0049] In an embodiment, the present disclosure provides a pharmaceutical
composition comprising bempedoic acid, clopidogrel and aspirin.
[0050] Bempedoic acid is a medication administered for hypercholesterolemia
that inhibits the cholesterol biosynthesis pathway. The IUPAC name of the
compound is 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid. In an
embodiment, the composition comprises bempedoic acid in an amount ranging
from about 10% w/w to about 40% w/w with respect to the composition.
[0051] Clopidogrel inhibits platelet aggregation and is a drug used to prevent
heart attacks and stroke in a subject. The IUPAC name of the compound is methyl
(2S)-2-(2-chlorophenyl)-2-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)acetate. In

an embodiment, the composition comprises clopidogrel in an amount ranging
from about 10% w/w to about 30% w/w with respect to the composition.
[0052] Aspirin is an over the counter drug administered commonly for mild aches
or pains as an analgesic and as an antipyretic for moderate fever. The IUPAC
name of the compound is 2-acetyloxybenzoic acid. In an embodiment, the
composition comprises aspirin in an amount ranging from about 10% w/w to
about 30%) w/w with respect to the composition.
[0053] In an embodiment, the active ingredients may be administered
sequentially, or simultaneously, either in combined dosage forms or in separate
dosage forms for substantially simultaneous delivery.
[0054] In a specific embodiment, the present disclosure provides a pharmaceutical
formulation comprising bempedoic acid, clopidogrel, aspirin, and one or more
pharmaceutically acceptable excipient(s).
[0055] In one embodiment, the present disclosure provides a pharmaceutical
formulation comprising bempedoic acid, clopidogrel, aspirin, and one or more
pharmaceutically acceptable excipient(s); wherein bempedoic acid, clopidogrel
and aspirin are in discrete units; and wherein bempedoic acid and clopidogrel are
in immediate release form, and aspirin is in enteric coated form.
[0056] In an embodiment, the formulation comprises bempedoic acid in an
amount ranging from about 10%> w/w to about 40% w/w with respect to the
formulation. In a preferred embodiment, the formulation comprises bempedoic
acid in an amount ranging from about 10%> w/w to about 35% w/w with respect to
the formulation.
[0057] In an embodiment, the formulation comprises clopidogrel in an amount
ranging from about 10%> w/w to about 30% w/w with respect to the formulation.
In a preferred embodiment, the formulation comprises clopidogrel in an amount
ranging from about 10% w/w to about 15% w/w with respect to the formulation.
[0058] In an embodiment, the formulation comprises aspirin in an amount ranging
from about 10% w/w to about 30% w/w with respect to the formulation. In a
preferred embodiment, the formulation comprises aspirin in an amount ranging
from about 10% w/w to about 15% w/w with respect to the formulation.

[0059] In an embodiment, the active ingredients may be present in any of their pharmaceutically acceptable forms. The pharmaceutically acceptable forms include pharmaceutically acceptable and therapeutically effective forms including their salts, solvates, hydrates, or prodrugs.
[0060] In an embodiment, clopidogrel may be present in the form of clopidogrel bisulphate, clopidogrel besylate or their combination.
[0061] In an embodiment, the excipient may be selected from fillers, binders, lubricants, glidants, swelling agents, sustained-release agents, coating agents, coloring agent, flavoring agent, diluents, disintegrating agents, pH modifiers, solvent, carrier or combinations thereof. However, a person of skill in the art would understand that any other excipient(s) may be employed in the formulation without going beyond the spirit and scope of the present disclosure. [0062] In an embodiment, the excipient may be selected from lactose, anhydrous lactose, sorbitol, sucrose, tragacanth, microcrystalline cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose hypromellose cellulose, croscarmellose, povidone, crospovidone, poloxamer, hydrogenated vegetable oils, citric acid, magnesium oxide, isopropyl alcohol, kaolin, silicon dioxide, silicon, colloidal anhydrous silicon, colloidal silicon dioxide, silicon, silica, fumed silica, stearic acid, magnesium stearate, sodium starch glycolate, glyceryl monostearate, sodium lauryl sulphate, sodium stearyl fumerate, starch, titanium dioxide, talc, water, methylene dichloride, castor oil, hydrogenated castor oil, polyethylene alcohol, polyethylene glycol, polyvinyl alcohol, lecithin, polysorbate, anhydrous silica, iron oxide, dichloromethane, acrylic acid based coating material, gelatin, coating materials such as, but not limited to, Opadry® enteric white 940580000, Seal Opadry® clear 03H9229, Tab Coat 580051, Opadry® White 85F18422; or combinations thereof.
[0063] In an embodiment, the formulation may be present in the form of a solid or a liquid. In an embodiment, the formulation may be present in the form of tablets, pellets, capsules, granules, sachets, lozenges, liquids, suspension, gel, micro-particles, or nano-particles.

[0064] In an embodiment, the formulation may be present in the form of a solid dosage form for oral administration. Specifically, the formulation may be a tablet formulation, granule formulation, capsule formulation or pellet formulation. [0065] In a preferred embodiment, the formulation may be in the form of a hard-gelatin capsule or cellulose capsule. In an embodiment, the capsule may have a size of 0, 00, 000, 1, 2, 3, 4 or 5. Preferably the capsule is sized 00. [0066] In a preferred embodiment, the formulation is a capsule formulation comprising the actives formulated as pellets, granules or tablets. [0067] In an embodiment, bempedoic acid may be present in an immediate release form of a solid, or a liquid. In a specific embodiment, bempedoic acid may be present in an immediate release form of tablets, pellets or granules. [0068] In a specific embodiment, the formulation may comprise one or more immediate release tablets comprising bempedoic acid. In an embodiment, the tablet comprises bempedoic acid along with pharmaceutically acceptable excipients including, but not limited to, lactose, microcrystalline cellulose, isopropyl alcohol, colloidal silicon dioxide, hydroxypropyl cellulose, sodium starch glycolate, magnesium stearate, dicalcium phosphate, starch, polyvinyl pyrrolidone, Opadry® White 85F18422, starch, sodium lauryl sulphate, talc, magnesium stearate, water, dichloromethane, or combinations thereof. [0069] In an embodiment, a tablet may comprise bempedoic acid in a range of about 40% w/w to about 80% w/w. In an embodiment, the pharmaceutically acceptable excipient maybe present in the range of about 20% w/w to about 60% w/w.
[0070] In a specific embodiment, the formulation comprises immediate release granules comprising bempedoic acid. In an embodiment, the granules may comprise bempedoic acid along with pharmaceutically acceptable excipients including lactose, microcrystalline cellulose, isopropyl alcohol, colloidal silicon dioxide, hydroxypropyl cellulose, sodium starch glycolate, magnesium stearate, dicalcium phosphate, starch, polyvinyl pyrrolidone, Opadry® White85F 18422, starch, sodium lauryl sulphate, talc, magnesium stearate, wateror combinations thereof.

[0071] In an embodiment, granules may comprise bempedoic acid in a range of about 40% w/w to about 80% w/w. In an embodiment, the pharmaceutically acceptable excipient maybe present in the range of about 20% w/w to about 60% w/w.
[0072] In an embodiment, clopidogrel may be present in an immediate release form of a solid or a liquid. In a specific embodiment, clopidogrel may be present as immediate release tablets, pellets or granules.
[0073] In a specific embodiment, the formulation may comprise one or more immediate release tablets comprising clopidogrel. In an embodiment, the tablet comprises clopidogrel bisulphate along with pharmaceutically acceptable excipients including anhydrous lactose, microcrystalline cellulose, crospovidone, hydrogenated castor oil, stearic acid, hydrophobic colloidal anhydrous silica, colloidal silicon dioxide, Seal Opadry® Clear 03H9229, Tab Coat 580051, talc, titanium dioxide, HPC, HPMC, polyethylene glycol, iron oxide, coating agent, dichloromethane, isopropyl alcohol, sodium lauryl sulphate, sodium stearyl fumarate ,or combinations thereof.
[0074] In an embodiment, a tablet may comprise clopidogrel in a range of about 30%) w/w to about 70% w/w. In an embodiment, the pharmaceutically acceptable excipients maybe present in the range of about 30% w/w to about 70% w/w. [0075] In an embodiment, aspirin may be present in an enteric coated form of solid. In a specific embodiment, aspirin may be present as an enteric coated tablet or pellet.
[0076] In a specific embodiment, the formulation may comprise one or more enteric coated tablets comprising aspirin. In an embodiment, the tablet comprises aspirin along with pharmaceutically acceptable excipients including starch, microcrystalline cellulose, glyceryl monostearate, colloidal silicon dioxide, seal Opadry® clear 03kl9229, dichloromethane, isopropyl alcohol, Opadry® enteric white 940580000, titanium dioxide, talc, water, or combinations thereof. [0077] In an embodiment, one tablet may comprise aspirin in an amount range of about 30%) w/w to about 60% w/w. In an embodiment, one tablet may comprise excipients in an amount range of about 40% w/w to about 70% w/w.

[0078] In one embodiment, the present disclosure provides a pharmaceutical formulation comprising: (a) one or more immediate release tablet(s) of bempedoic acid comprising bempedoic acid and one or more pharmaceutically acceptable excipient(s); (b) one or more immediate release tablet(s) of clopidogrel comprising clopidogrel and one or more pharmaceutically acceptable excipient(s); and (c) one or more enteric coated tablet(s) of aspirin comprising aspirin and one or more pharmaceutically acceptable excipient(s).
[0079] In one embodiment, the present disclosure provides a pharmaceutical formulation comprising bempedoic acid, clopidogrel, aspirin, and one or more pharmaceutically acceptable excipient(s); wherein the formulation comprises one or more immediate release tablet(s) of bempedoic acid, one or more immediate release tablet(s) of clopidogrel and one or more enteric coated tablet(s) of aspirin. In one embodiment, the formulation comprises one or more immediate release tablet(s) of bempedoic acid comprising about 60% w/w to about 70% w/w of bempedoic acid; one or more immediate release tablet(s) of clopidogrel comprising about 30% w/w to about 40% w/w of clopidogrel; and one or more enteric coated tablet(s) of aspirin comprising about 40% w/w to about 50% w/w of aspirin.
[0080] In a preferred embodiment, the present disclosure provides a pharmaceutical formulation comprising bempedoic acid, clopidogrel, aspirin, and one or more pharmaceutically acceptable excipient(s); wherein the formulation comprises two immediate release tablets of bempedoic acid each comprising about 90mg of bempedoic acid; one immediate release tablet of clopidogrel bisulphate comprising about lOOmg of clopidogrel bisulphate and one enteric coated tablet of aspirin comprising about 75mg of aspirin.
[0081] In one embodiment, the present disclosure provides a pharmaceutical formulation comprising: (a) one or more immediate release granules of bempedoic acid comprising bempedoic acid and one or more pharmaceutically acceptable excipient(s); (b) one or more immediate release tablet(s) of clopidogrel comprising clopidogrel and one or more pharmaceutically acceptable excipient(s);

and (c) one or more enteric coated tablet(s) of aspirin comprising aspirin and one or more pharmaceutically acceptable excipient(s).
[0082] In one embodiment, the formulation comprises immediate release granules of bempedoic acid comprising about 60% w/w to about 70% w/w of bempedoic acid; one or more immediate release tablet(s) of clopidogrel comprising about 60%) w/w to about 70% w/w of clopidogrel; and one or more enteric coated tablet(s) of aspirin comprising about 50% w/w to about 60%> w/w of aspirin. [0083] In a preferred embodiment, the present disclosure provides a pharmaceutical formulation comprising bempedoic acid, clopidogrel, aspirin, and one or more pharmaceutically acceptable excipient(s); wherein the formulation comprises 274 mg of granules of bempedoic acid comprising about 180mg of bempedoic acid, one immediate release tablet of clopidogrel bisulphate comprising about lOOmg of clopidogrel bisulphate and one enteric coated tablet of aspirin comprising about 75mg of aspirin.
[0084] In an embodiment, the present disclosure provides a pharmaceutical formulation for once or twice daily oral administration.
[0085] The formulations are safe, stable and effective. In an embodiment, the present disclosure provides a pharmaceutical composition for once or twice daily oral administration.
[0086] In an embodiment, composition and formulation can show synergistic action and improve patient compliance.
[0087] In an embodiment of the present disclosure, the pharmaceutical formulation may further comprise additional active ingredient(s) selected from one or more of group consisting of: ace-inhibitors, anti-Alzheimer's agents, anti-anginal drugs, anti-arrhythmias, anti-asthmatics, anti-cholesterolemics, analgesics, anesthetics, anti-convulsants, anti-depressants, anti-diabetic agents, anti-diarrhea preparations, antidotes, anti-emetics, anti-histamines, anti-hypertensive drugs, anti-inflammatory agents, anti-lipid agents, anti-manics, anti-migraines, anti-nauseants, anti-stroke agents, anti-thyroid preparations, anti-tumor drugs, anti¬viral agents, acne drugs, alkaloids, amino acid preparations, anti-tussives, anti-uricemic drugs, anti-viral drugs, anabolic preparations, systemic and non-systemic

anti-infective agents, anti-neoplasties, anti-parkinsonian agents, anti-rheumatic agents, anxiolytics, anti-psychotics, appetite stimulants, biological response modifiers, blood modifiers, bone metabolism regulators, bronchodilators, cardiovascular agents, central nervous system stimulates, cholinesterase inhibitors, contraceptives, decongestants, dietary supplements, dopamine receptor agonists, endometriosis management agents, enzymes, erectile dysfunction agents, fertility agents, gastrointestinal agents, H2-antagonists, homeopathic remedies, hormones, hypercalcemia and hypocalcemia management agents, immunomodulators, immunosuppressives, migraine preparations, motion sickness treatments, muscle relaxants, non-steroidal anti-inflammatories (NSAID's), obesity management agents, osteoporosis preparations, oxytocics, parasympatholytics, parasympathomimetics, prostaglandins, psychotherapeutic agents, respiratory agents, sedatives, serotonin 5-HT3 receptor antagonists, smoking cessation aids, sympatholytics, tremor preparations, urinary tract agents, vasodilators, laxatives, antacids, ion exchange resins, anti-pyretics, appetite suppressants, expectorants, anti-anxiety agents, anti-ulcer agents, anti-inflammatory substances, coronary dilators, cerebral dilators, peripheral vasodilators, psycho-tropics, stimulants, anti-hypertensive drugs, vasoconstrictors, migraine treatments, antibiotics, tranquilizers, anti-psychotics, anti-tumor drugs, anti-coagulants, anti-thrombotic drugs, hypnotics, anti-emetics, anti-nauseants, anti-convulsants, neuromuscular drugs, hyper- and hypo-glycemic agents, thyroid and anti-thyroid preparations, diuretics, anti-spasmodics, anti-obesity drugs, erythropoietic drugs, anti-asthmatics, cough suppressants, mucolytics, DNA and genetic modifying drugs, and combinations thereof.
[0088] In an embodiment, the present disclosure provides a process for preparing a pharmaceutical formulation comprising bempedoic acid, clopidogrel and aspirin. [0089] In an embodiment, the present disclosure provides a process for preparing a pharmaceutical formulation comprising bempedoic acid, clopidogrel, aspirin and one or more pharmaceutically acceptable excipient(s); wherein bempedoic acid, clopidogrel and aspirin are in discrete units; and wherein bempedoic acid and clopidogrel are in immediate release form, and aspirin is in enteric coated form.

[0090] In an embodiment, the present disclosure provides a process for preparing a pharmaceutical formulation comprising the steps of: (a) preparing an immediate release tablet or granule of bempedoic acid; (b) preparing an immediate release tablet of clopidogrel; (c) preparing an enteric coating tablet of aspirin; and (d) adding the immediate release tablet or granule of bempedoic acid, immediate release tablet of clopidogrel and enteric coating tablet of aspirin in a capsule to give the pharmaceutical formulation.
[0091] The methods of preparation of the tablets and granules are those well-known in the art.
[0092] In an embodiment, the processes of preparing the formulation and/or composition may involve the steps of milling (wet or dry), weighing, packaging, binder preparation, binding, mixing, lubricating, granulating, melt granulating, blending, sifting, sieving, sizing, direct compression, freeze drying, compaction, refining, tableting or combinations thereof well-known in the art. [0093] In an embodiment, the present disclosure provides a method of management of dyslipidemia and associated co-morbidities in a subject by administering a pharmaceutically effective amount of the pharmaceutical composition or formulation as recited above.
[0094] In an embodiment, the present disclosure provides a method of treatment, amelioration or prevention of dyslipidemia and associated co-morbidities in a subject by administering a pharmaceutically effective amount of the pharmaceutical composition or formulation as recited above. [0095] In an embodiment, the present disclosure provides a method of management o a subject with an increased risk of cardiovascular diseases by administering a pharmaceutically effective amount of the pharmaceutical composition or formulation as recited above.
[0096] The pharmaceutically effective amount may be determined by a trained physician based on the subject being treated, age, gender, weight, severity of disease, medical history, among other factors. In an embodiment, the composition or formulation decreases serum cholesterol in the subject.

[0097] In an embodiment, the dyslipidemia may be associated with atherosclerotic arterial disease with risk of Myocardial infarction, altered platelet function, hypercholesterolemia, stroke, hypertension, or peripheral vascular disease. [0098] In an embodiment, the present disclosure provides use of the pharmaceutical formulation for the treatment, amelioration or prevention of dyslipidemia and associated co-morbidities.
[0099] In an embodiment, the present disclosure provides the pharmaceutical formulation for use in treatment, amelioration or prevention of dyslipidemia and other co-morbidities.
[00100] While the foregoing describes various embodiments of the disclosure, other and further embodiments of the disclosure may be devised without departing from the basic scope thereof. The invention is not limited to the described embodiments, versions or examples, which are included to enable a person having ordinary skill in the art to make and use the invention when combined with information and knowledge available to the person having ordinary skill in the art. EXAMPLES
[00101] The disclosure will now be illustrated with working examples, which is intended to illustrate the working of disclosure and not intended to take restrictively to imply any limitations on the scope of the present disclosure. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which this disclosure belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice of the disclosed methods and compositions, the exemplary methods, devices and materials are described herein. It is to be understood that this disclosure is not limited to particular methods, and experimental conditions described, as such methods and conditions may vary. Example 1
Immediate release tablets of Bempedoic acid and preparation thereof [00102] Bempedoic acid immediate release tablets of 90 mg were prepared based on the composition of Table No. 1 and the procedure provided below:

Table No. 1: Components of Bempedoic acid tablets

S.No. INGREDIENTS mg/Tab w/w %
1 Bempedioic acid 90 62.5
2 Lactose 15 10.4
3 Microcrystalline Cellulose 23.6 16.4
Binder 0.0
4 Hydroxypropyl Cellulose (HPC) 4 2.8
5 Isopropyl alcohol (IPA) q.s. q.s.
Lubrication 0.0
6 Colloidal Silicon dioxide 1.2 0.8
7 sodium starch glycolate (SSG) 5 3.5
8 Magnesium stearate 1.2 0.8
Total 140
Coating 0.0
9 Opadry® White 85F18422 4 2.8
10 IP A 70% q.s. q.s.
11 MDC 30% q.s. q.s.
Total Weight 144 mg 100
1.1. Sifting
Bempedoic acid, lactose, and microcrystalline cellulose were sifted through a 40# sieve and dry mixed for 10 minutes.
1.2 Binder preparation
Sufficient quantity of isopropyl alcohol was taken to dissolve HPC till a clear solution was obtained.
1.3 Binding
Dry mixed powder of 1.1 and binder of 1.2 were mixed slowly till desired consistency of wet mass was achieved. The wet mass was then passed through a sieve #08.
1.4 Drying
Air drying was performed for 10 minutes and if applicable, heating was performed for 10 minutes at 60°C temperature.
1.5 Sizing
The dried granules were passed through # 24 sieve.
1.6 Lubrication and blending

Lubrication materials colloidal silicon dioxide, sodium starch glycolate, and magnesium stearate were sifted through 40#. The sifted materials were blended for 12 minutes without magnesium stearate and for 3 minutes with magnesium stearate.
1.7 Coating
Sufficient quantity of IPA was added to Opadry® White 85F18422 with continuous stirring for 15 minutes. Then MDC was added with continuous stirring, colloided for 20 minutes and filtered through 200#.
1.8 Tableting
The tablets were punched to size - 7.00 mm, round, concave & plain.
Example 2
Immediate release Clopidogrel tablets and preparation thereof
[00103] Clopidogrel tablets of 75 mg were prepared based on the composition of
Table No. 2 and the dry mixing procedure below:
Table No. 2: Components of Clopidogrel tablets

S.No. Ingredients mg/Tab w/w%
1 Clopidogrel Bisulphate** 97.88 32.63
2 Anhydrous lactose 40 13.33
3 Microcrystalline Cellulose PH102 80.24 26.75
4 Crospovidone 40 13.33
5 Hydrogenated Castor Oil 20 6.67
Lubrication
6 Hydrophobic Colloidal Anhydrous silicon dixode 0.8 0.27
7 Stearic Acid 20 6.67
Total Weight 298.92
Seal Coating
8 Seal Opadry® White 85F18422 0.6 0.20
9 Talc 0.2 0.07
10 Titanium dioxide 0.2 0.07
11 Colour Red Oxide Of Iron Lake 0.08 0.03
12 IPA (30%) q.s. q.s.
13 Dichloromethane (70%) q.s. q.s.
Total wt. 300 100

** Factor for Clopidogrel Bisulphate eq. to Clopidogrel - 1.304
2.1 Sifting and blending
Clopidogrel bisulphate, lactose anhydrous, microcrystalline cellulose PH 102, crospovidone, and hydrogenated castor oil were sifted through 40# sieve and all ingredients were mixed for 15 minutes.
2.2 Lubrication and blending
Lubrication materials hydrophobic colloidal anhydrous silicon dioxide and stearic acid were sifted through 40#. Mixture of 2.1 was blended with hydrophobic colloidal anhydrous silicon dioxide and red oxide of iron for 10 minutes. Further, this was blended for 3 minutes with stearic acid.
2.3 Coating I
Sufficient quantity of IP A was added to Seal Opadry® White 85F18422, titanium dioxide, and talcum with continuous stirring for 15 minutes. Then MDC was added with continuous stirring, colloided for 20 minutes and filtered through 200#.
2.4 Tableting
Tablets were punched to size - 9.00 mm, round, concave & plain.
Example 3
Enteric coated tablets of Aspirin and preparation thereof
[00104] Enteric coated tablets of Aspirin 75 mg were prepared based on the
composition of Table No. 3 and the dry mixing procedure below:
Table No. 3: Components of Aspirin tablets

S.No. INGREDIENTS mg/Tab w/w %
1 Aspirin 75 47.47
2 Starch® 1500 30.9 19.56
3 Microcrystalline cellulose (MCC)PH112 28 17.72
Lubrication
4 Glyceryl mono stearate 2 1.27
5 Colloidal silicon dioxide 0.5 0.32
Total 136.4
Coating material
Seal Coat
6 Seal Opadry® clear 03kl9229 5 3.16

7 IP A (30%) q.s. q.s.
8 MDC (70%) q.s. q.s.
Enteric Coat
9 Opadry® enteric white 940580000 14.7 9.68
10 Ti02 0.3 0.19
11 Talcum 1 0.63
12 Purified water (70%) q.s. q.s.
13 IP A (30%) q.s. q.s.
Total Weight 158 mg 100
3.1 Sifting and blending
Aspirin, Starch® 1500, and microcrystalline cellulose PH 112 were sifted through 40# sieve and dry mixed for 10 minutes. All the ingredients were mixed for 15 Minutes.
3.2 Lubrication and blending
Lubrication materials- glyceryl monostearate, and colloidal silicon dioxide were sifted through 40# and blended with the mixture of 3.1 for 12 minutes without glyceryl monostearate and for 3 minutes with glyceryl monostearate.
3.3 Coating: I (Seal Coating)
Sufficient quantity of IPA was added to Seal Opadry® Clear 03kl9229 with continuous stirring for 15 minutes. Then MDC was added with continuous stirring. The solution was colloided for 15 minutes and the seal coating solution was passed through 200#.
3.4 Enteric coating:
Sufficient quantity of IPA was added to Opadry® enteric white 940580000, titanium dioxide, and talcum with continuous stirring for 15 min. Then MDC was added with continuous stirring followed by purified water with continuous stirring. Colloided the solution for 20 minutes and filtered the solution with 200#.
3.5 Tableting
The tablet was punched to size - 7.00 mm, round, concave & plain.
Example 4
A Capsule comprising immediate release tablets of bempedoic acid,
immediate release tablet of clopidogrel and enteric coated tablet of aspirin
preparation

[00105] Two tablets of bempedoic acid as per Example 1, one tablet of clopidogrel as per Example 2 and one tablet of aspirin of Example 3 were filed in an elongated white/off white colored capsule cell of size 00 in accordance with the capsule filling process known in the art to give a formulation as per the present disclosure. Example 5
Immediate release granules of Bempedoic acid and preparation thereof [00106] Bempedoic acid granules of 180 mg were prepared based on the composition of Table No. 4 and the procedure provided below:
Table No. 4: Components of Bempedoic acid granules

S.No. Ingredients mg/Tab w/w %
1 Bempedioic acid 180 66
2 Starch 22 8
3 Sodium starch glycolate 12 4
4 Sodium lauryl sulphate 5 1.8
5 Microcrystalline cellulose PHI 02 31 11
Binder
6 HPC 6 2
7 Purified water q.s. q.s.
Lubrication
8 Colloidal Silicon dioxide 6 2
9 Talcum 4 1
10 Magnesium stearate 8 3
Total weight 274
Granulation procedure
5.1 Sifting
Bempedoic acid, starch, microcrystalline cellulose PHI02, sodium starch glycolate, and sodium lauryl sulphate were sifted through a 40# sieve and dry mixed for 15 minutes.
5.2 Binder preparation
Sufficient quantity of purified water was taken to dissolve HPC till a clear solution was obtained.
5.3 Binding

Dry mixed powder of 5.1 and binder of 5.2 were mixed slowly till desired consistency of wet mass was achieved. The wet mass was then passed through sieve #08.
5.4 Drying
Air drying was performed for 10 minutes and if applicable, heating was performed for 10 minutes at 60°C temperature.
5.5 Sizing
The dried granules were passed through # 20 sieve.
5.6 Lubrication and blending
Lubrication materials colloidal silicon dioxide, talcum and magnesium stearate
were sifted through 40#. The sifted materials were blended for 15 minutes with
granules of 5.5 without magnesium stearate and for 5 minutes with magnesium
stearate.
Example 6
Immediate release Clopidogrel tablets and preparation thereof
[00107] Clopidogrel tablets of 75 mg were prepared based on the composition of
Table No. 5 and the dry mixing procedure below:
Table No. 5: Components of Clopidogrel tablets

S.No. Ingredients mg/Tab w/w%
1 Clopidogrel Bisulphate** 99.16 66
2 Anhydrous lactose 29.34 20
3 Sodium lauryl sulphate 2.5 1.67
4 Crospovidone 5 3
Binder
5 HPC 2 1
6 IPA 25 16.1
Lubrication
7 Colloidal silicon dioxide 3 2
8 Sodium stearyl fumarate 4 3
Avg. wt. of uncoated tablet(mg) 150
Coating Materials
9 HPMCE5 4.32
10 Titanium dioxide 0.3
11 Color Ferric Oxide red 0.01
12 PEG 6000 0.3

13 IPA 50% 48
14 MDC 50% 48
Avg. wt. of coated tablet(mg) 155
** Factor for Clopidogrel Bisulphate eq. to Clopidogrel - 1.304
6.1 Sifting
Clopidogrel, anhydrous lactose, sodium lauryl sulphate and crospovidone were sifted through a 40# sieve and dry mixed for 15 minutes.
6.2 Binder preparation
Sufficient quantity of isopropyl alcohol was taken to dissolve HPC till a clear solution was obtained.
6.3 Binding
Dry mixed powder of 6.1 and binder of 6.2 slowly till desired consistency of wet mass was achieved. The wet mass was then passed through a sieve #08.
6.4 Drying
Air drying was performed for 10 minutes and if applicable, heating was performed for 10 minutes at 60°C temperature.
6.5 Sizing
The dried granules were passed through # 24 sieve.
6.6 Lubrication and blending
Lubrication materials colloidal silicon dioxide, and sodium stearyl fumarate were sifted through 40#. The sifted materials were blended for 15 minutes with granules of 6.5 without sodium stearyl fumarate and for 5 minutes with sodium stearyl fumarate.
6.7 Coating
HPMC E5 was dissolved in IPA for 20 min., after 20 min Ti02 & colour ferric oxide red were added & stirred for 15 min. PEG6000 was dissolved separately in MDC till a clear solution was obtained, and then MDC solution was added in HPMC E5 solution & stirred for 20 min. & sifted with 200# nylon cloth.
6.8 Tableting
The tablets were punched to size - 7.00 mm, round, concave & plain.

Example 7
Enteric coated tablets of Aspirin and preparation thereof
[00108] Aspirin tablets of 75 mg were prepared based on the composition of
Table No. 6 and the dry mixing procedure below:
Table No. 6: Components of Aspirin tablets

S.No. INGREDIENTS mg/Tab w/w%
1 Aspirin 75.28 54.74
2 Starch® 1500 31.5 22.9
3 MCC 112 28 20.44
LUBRICATION
4 Glyceryl mono stearate 2 1.46
5 Colloidal silicon dioxide 0.5 0.36
Total 137
Coating material
Seal Coat
6 seal Opadry® clear 03kl9229 5 3.6
7 IPA 40% q.s. q.s.
8 MDC 60% q.s. q.s.
Enteric Coat
9 Opadry® enteric white 940580000 14.7 10.7
10 Ti02 0.3 0.21
11 Talcum 1 0.72
12 Purified water 30% q.s. q.s.
13 IPA 70% q.s. q.s.
Total Weight 158 mg 100
7.1 Sifting
Aspirin, starch 1500, and Microcrystalline cellulose 112 were sifted through a 40# sieve.
7.2 Blending
The ingredients of 7.1 were blended for 20 mins.
7.3 Lubrication
Lubrication materials colloidal silicon dioxide and glyceryl monostearate were sifted through 40#. The sifted materials were blended for 15 minutes without glyceryl monostearate and for 5 minutes with glyceryl monostearate.

7.4 Seal coating
Seal Opadry® clear 03kl9229 was dissolved in IPA for 20 min., and after 20 min MDC was added & stirred for 15 min and sifted by 200# nylon cloth.
7.5 Enteric coating
Opadry® enteric white 940580000 was dissolved in purified water & colloided for 15 min. HO2 & Talcum were added and colloided for 20 min. After 20 min, IPA was added & again colloided for 10 min followed by filtration with 200# nylon cloth.
7.6 Tableting
The tablets were punched to size - 7.0 mm, round, concave & plain.
Example 8
A capsule comprising immediate release granules of bempedoic acid,
immediate release tablet of clopidogrel and enteric coated tablet of aspirin
preparation
[00109] Granules of bempedoic acid as per Example 5, one tablet of clopidogrel
as per Example 6 and one tablet of aspirin of Example 7 were filed in a capsule
cell of size 00 in accordance with the capsule filling process known in the art.
[00110] From the foregoing, it will be appreciated that, although specific
embodiments of the invention have been described herein merely for purposes of
illustration, various modifications may be made without deviating from the spirit
and scope of the invention and should not be construed so as to limit the scope of
the invention or the appended claims in any way.

We Claim:
1. A pharmaceutical formulation comprising bempedoic acid, clopidogrel, aspirin, and one or more pharmaceutical^ acceptable excipient(s); wherein bempedoic acid, clopidogrel and aspirin are in discrete units; and wherein bempedoic acid and clopidogrel are in immediate release form, and aspirin is in enteric coated form.
2. The formulation as claimed in claim 1, wherein the formulation comprises bempedoic acid in an amount ranging from 10%> w/w to 40% w/w with respect to the formulation.
3. The formulation as claimed in claim 1, wherein the formulation comprises clopidogrel in an amount ranging from 10%> w/w to 30% w/w with respect to the formulation.
4. The formulation as claimed in claim 1, wherein the formulation comprises aspirin in an amount ranging from 10%> w/w to 30% w/w with respect to the formulation.
5. The formulation as claimed in claim 1, wherein the excipient is selected from fillers, binders, lubricants, glidants, swelling agents, sustained-release agents, coating agents, coloring agent, flavoring agent, diluents, disintegrating agents, pH modifiers, solvent, carrier or combinations thereof.
6. The formulation as claimed in claim 1, wherein the formulation is present in the form of a solid dosage form for oral administration selected from a tablet formulation, granule formulation, capsule formulation or pellet formulation.
7. The formulation as claimed in claim 1, wherein bempedoic acid is present as immediate release granules.
8. The formulation as claimed in claim 7, wherein the granules comprise
bempedoic acid in a range of 40% w/w to 80%> w/w.
9. The formulation as claimed in claim 1, wherein bempedoic acid is present as
one or more immediate release tablet(s).
10. The formulation as claimed in claim 9, wherein each tablet comprises
bempedoic acid in a range of 40% w/w to 80%> w/w.

11. The formulation as claimed in claim 1, wherein clopidogrel is present as one or more immediate release tablet(s).
12. The formulation as claimed in claim 11, wherein each tablet comprises clopidogrel in a range of 30% w/w to 70% w/w.
13. The formulation as claimed in claim 1, wherein aspirin is present as one or more enteric coated tablet(s).
14. The formulation as claimed in claim 13, wherein each tablet comprises aspirin in a range of 30% w/w to 60% w/w.
15. The formulation as claimed in claim 1, wherein the formulation comprises one or more immediate release tablet(s) of bempedoic acid comprising 60% w/w to 70%) w/w of bempedoic acid; one or more immediate release tablet(s) of clopidogrel comprising 30% w/w to 40% w/w of clopidogrel; and one or more enteric coated tablet(s) of aspirin comprising 40% w/w to 50% w/w of aspirin.
16. The formulation as claimed in claim 1, wherein the formulation comprises immediate release granules of bempedoic acid comprising 60% w/w to 70% w/w of bempedoic acid; one or more immediate release tablet(s) of clopidogrel comprising 60% w/w to 70% w/w of clopidogrel; and one or more enteric coated tablet(s) of aspirin comprising 50% w/w to 60% w/w of aspirin.
17. A process for preparing a pharmaceutical formulation comprising the steps of: (a) preparing an immediate release tablet or granule of bempedoic acid; (b) preparing an immediate release tablet of clopidogrel; (c) preparing an enteric coating tablet of aspirin; and (d) adding the immediate release tablet or granule of bempedoic acid, immediate release tablet of clopidogrel and enteric coating tablet of aspirin in a capsule to give the pharmaceutical formulation.