Pharmaceutical composition comprising rosuvastatin and acetylsalicylic acid, preparation process and uses thereof.

Description

1 / 50 Pharmaceutical composition comprising rosuvastatin and acetylsalicylic acid, preparation process and uses thereof. TECHNICAL AREA

[001] The present invention relates to the field of the pharmaceutical industry and more particularly to a pharmaceutical composition comprising rosuvastatin and acetylsalicylic acid, a process for its preparation and uses. BACKGROUND

[002] Cardiovascular events represent one of the main causes of morbidity and mortality in the world, constituting a public health challenge of significant proportions. In recent decades, there has been an alarming increase in the incidence of these events in the population, highlighting the urgency of implementing effective prevention and treatment strategies.

[003] The use of medications such as statins to control cholesterol, antihypertensives to regulate blood pressure, and antiplatelet drugs to prevent blood clots plays a key role in reducing cardiovascular risk.

[004] In this regard, comparative studies have been published between different doses of rosuvastatin and different dosages of other statins, such as atorvastatin, pravastatin, and simvastatin, mainly in relation to cholesterol-lowering performance and adverse events. Rosuvastatin showed better cholesterol-lowering performance, even at lower dosages, than atorvastatin and the other indicated statins.

[005] Rosuvastatin is a completely synthetic drug, a member of the statin family, and is a lipid-lowering agent whose chemical name is bis[(E)-7-[4-(4-fluorophenyl)-6-isorpropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid]. A Petition 870250081794, dated 11 / 09 / 2025, page 14 / 86 Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, a rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A into mevalonate, a precursor of cholesterol.

[006] Acetylsalicylic acid (ASA), commonly known as aspirin, is a nonsteroidal anti-inflammatory drug (NSAID) belonging to the salicylate family; its chemical name is 2-(acetyloxy)benzoic acid; salicylic acid acetate. ASA interferes with the production of prostaglandins in various organs and tissues through acetylation of the cyclooxygenase enzyme. By preventing the synthesis and release of prostaglandins in inflammatory processes, ASA can prevent the sensitization of pain receptors.

[007] Considering the mechanisms of action and effects on the human body, formulations have been developed that comprise a combination of the active ingredients rosuvastatin and acetylsalicylic acid for the secondary prevention of cardiovascular events. However, it is known that acetylsalicylic acid has acidic properties, while rosuvastatin incorporates alkaline salts, so the mixture of acetylsalicylic acid and rosuvastatin can result in the hydrolysis of acetylsalicylic acid, generating degradation of rosuvastatin. Rosuvastatin salts are particularly unstable, being susceptible to heat, humidity, low pH, and light. Acetylsalicylic acid is an ester that is easily hydrolyzed in the presence of moisture to form salicylic acid. Furthermore, according to its type II biopharmaceutical classification, rosuvastatin exhibits high permeability and low solubility, which jeopardizes its stability and, consequently, the pharmaceutical composition or form containing it.To try to solve the problem described above, pharmaceutical compositions have been proposed that combine these active ingredients in separate entities in a single solid dosage form, whether tablets, particles, granules, pellets or capsules. Petition 870250081794, dated 11 / 09 / 2025, page 15 / 86 3 / 50

[008] U.S. Patent Application 2007 / 116756 A1, published May 24, 2007 (DR. REDDY LAB. INC.), describes stable pharmaceutical compositions of cardiovascular therapeutic agents comprising a combination of effective dosages of a cholesterol-lowering agent or its salts, solvates, pharmaceutically acceptable enantiomers, or mixtures thereof in a single dosage form and aspirin. The amount of aspirin ranges from 25 to 600 mg. Useful agents for lowering cholesterol include statins, which include, but are not limited to, atorvastatin, pravastatin, cerivastatin, fluindostatin, fluvastatin, lovastatin, mevastatin, rosuvastatin, pitavastatin, dalvastatin, and velostatin. Although the application describes the compositions as stable, stability is only proven for one composition comprising lisinopril, atenolol, and aspirin, and that test was conducted over a period of 4 weeks.In contrast, for the composition of the present invention comprising rosuvastatin and acetylsalicylic acid, its stability has been proven for 6 months.

[009] International application WO 2012 / 081905 published on June 21, 2012 (HANMI HOLDING, CO) describes a compound formulation for preventing or treating cardiovascular diseases comprising a first particle comprising an HMG-CoA reductase inhibitor and a basic additive, and a second particle comprising an aspirin core and an enteric coating layer, wherein the difference between the average diameters of said first and second particles is from 100 µm to 800 µm. Examples of HMG-CoA reductase inhibitors are rosuvastatin, lovastatin, atorvastatin, pravastatin, fluvastatin, pitavastatin, simvastatin, rivastatin, cerivastatin, velostatin, mevastatin and pharmaceutically acceptable salts thereof, precursors or a mixture thereof. The first particle may also comprise diluents and other excipients, such as disintegrants, Petition 870250081794, dated 11 / 09 / 2025, page 16 / 86 4 / 50 binders, lubricants, coating agents, fillers, rheology modifiers, crystallization retardants, solubilizers, pH modifiers, surfactants, emulsifiers or mixtures thereof. The second particle comprises an aspirin core and an enteric coating, which may include excipients such as plasticizers and lubricants. The present invention provides a pharmaceutical composition comprising a first phase of rosuvastatin and a second phase of stable acetylsalicylic acid, where only one of the phases is a granulate.

[010] Patent document WO 2012 / 11882 A1, published on January 26, 2012 (MAHMUT BILGIC), also describes a pharmaceutical composition comprising aspirin (acetylsalicylic acid) and atorvastatin and / or their pharmaceutically acceptable salts, hydrates, enantiomers, racemates, organic salts, inorganic salts, esters, polymorphs, crystalline forms, amorphous forms, and combinations thereof. The active ingredients are in separate units, present in a single dosage form. The units may be granules, powder, pellets, tablets, mini-tablets, micro-tablets, capsules, microcapsules, and combinations thereof. The highest bioavailability was found to be achieved in tablet and powder forms, with preference given to atorvastatin powder and aspirin tablets.In contrast, the present invention provides a pharmaceutical composition comprising a first phase of rosuvastatin and a second phase of acetylsalicylic acid, wherein preferably the first phase of rosuvastatin is a tablet and the second phase of acetylsalicylic acid is a granule.

[011] In turn, document US 2002 / 034546 A1, published on March 21, 2002 (ISMAT ULLAH & NEMICHAND B JAIN) describes a composition comprising a statin cholesterol-lowering agent and aspirin. Petition 870250081794, dated 11 / 09 / 2025, page 17 / 86 5 / 50 In some embodiments, each of the drugs is in separate units within a dosage unit. The separate forms include granules. Common excipients in the art and types thereof are helpful. However, statins do not include rosuvastatin; and in certain embodiments, aspirin is presented as coated granules.

[012] Document WO 2014 / 195421 A1, published on December 11, 2014 (FERRER INT., SA & FUNDACIÓN CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III), describes an orally administerable pharmaceutical dosage form for the treatment and / or prevention of cardiovascular diseases, comprising acetylsalicylic acid and an HMG-CoA reductase inhibitor selected from atorvastatin and rosuvastatin and salts thereof, the active ingredients being in two or more independent coated dosage units, comprising one or more water-soluble polymers in said coating, being free of water-insoluble polymers or an enteric polymer, wherein the coating is greater than 6 mg / cm2 and does not exhibit a modified release profile; where the independently coated dosing units are selected from the group consisting of tablets, particles, granules, pellets and capsules.The pharmaceutical composition of the present invention comprises a first phase of rosuvastatin and a second phase of acetylsalicylic acid; however, only one of the phases is coated.

[013] Document US2012 / 045505 A1, published February 23, 2012 (DR. REDDY LAB. INC.) describes a pharmaceutical formulation in capsule form containing at least one tablet, comprising as active ingredients: a cholesterol-lowering agent, aspirin, a renin-angiotensin system reducer and a beta-adrenergic receptor inhibitor or a diuretic, the active ingredients or a combination of two or more Petition 870250081794, dated 11 / 09 / 2025, page 18 / 86 6 / 50 of them being in the form of tablets, capsules or particles, where the cholesterol-lowering agent is physically separated from aspirin. The cholesterol-lowering agent may be lovastatin, atorvastatin, simvastatin, fluvastatin, rosuvastatin or pravastatin, their salts, esters, amides, prodrugs, metabolites, analogues, solvates, hydrates, enantiomers, polymorphs, derivatives and the like. According to the examples in this document, aspirin is in the form of a coated tablet; in contrast, the pharmaceutical composition of the present invention comprises a second phase of acetylsalicylic acid, which is in the form of granules.

[014] Patent document WO 2012 / 124973 A2, published on September 20, 2012 (BORYUNG PHARM), describes a capsule dosage form of a combined drug formulation for the treatment of cardiovascular diseases, comprising mini-tablets containing a cholesterol-lowering agent, a cholesterol-lowering stabilizer, and excipients, including an enteric coating on the surface thereof, with a diameter of 7.5 mm or less, and mini-tablets or mini-pellets of an antithrombotic agent and excipients, including an enteric coating on the surface thereof, with a diameter of 7.5 mm or less. The cholesterol-lowering agent may be rosuvastatin, rosuvastatin calcium, atorvastatin calcium, rivastatin, and pharmaceutically acceptable salts thereof. The stabilizer may be calcium phosphate. The preferred antithrombotic agent is acetylsalicylic acid.Similar to previous documents, acetylsalicylic acid is described as having an enteric coating, which can alter drug release; in contrast, the pharmaceutical composition of the present invention comprises an uncoated acetylsalicylic acid phase.

[015] Document WO 2004 / 80488 A1, published on September 23, 2004 (BAYER HEALTHCARE AG), generally describes a combination of Petition 870250081794, dated 11 / 09 / 2025, p. 19 / 86 7 / 50 Acetylsalicylic acid and a statin, in separate forms (tablets or capsules), each within a packaging material (blister). The document in question neither teaches nor suggests that drugs can be in only one pharmaceutical form.

[016] In turn, document WO 2011 / 96665 A2, published on August 11, 2011 (HANMI HOLDING, CO), describes a capsule-form formulation containing aspirin granules or pellets coated with a barrier containing a hydrophobic additive and granules or pellets of an HMG-CoA reductase inhibitor. Aspirin is available in quantities from 10 mg to 2 g. The HMG-CoA reductase inhibitor may be mevastatin, rosuvastatin, atorvastatin, lovastatin, pravastatin, pravastatin lactone, pitavastatin, bervastatin, velostatin, simvastatin, rivastatin, fluvastatin, cerivastatin, or isomers or salts and combinations thereof. The HMG-CoA reductase inhibitor is available in quantities from 5 mg to 80 mg. Unlike this document, the pharmaceutical composition of the present invention comprises acetylsalicylic acid (aspirin) without enteric coating.

[017] Document CN 1965843 A, published on May 23, 2007 (BEIJING HUAANFO MEDICAL RES CT), describes the use of a combination of aspirin and a statin cholesterol-lowering agent (simvastatin, pravastatin, lovastatin, fluvastatin, atorvastatin, rosuvastatin, pitavastatin) to prepare a medicament for the treatment of blood hyperviscosity. The aspirin is in the form of coated tablets, coated micropills, or coated dropper pills, where the coating is an enteric coating. As previously indicated, the pharmaceutical composition of the present invention comprises an acetylsalicylic acid phase that does not have an enteric coating.

[018] None of the state-of-the-art documents propose to improve the Petition 870250081794, dated 11 / 09 / 2025, page 20 / 86 8 / 50 stability of a pharmaceutical composition containing a statin and acetylsalicylic acid placing the said NSAID without coating, despite the already known problems of the susceptibility of statins to heat, humidity, low pH environments and light; or to drug interactions that can produce degradation products, which shortens their shelf life. On the other hand, rosuvastatin is sensitive to humidity, and typical granulation processes, such as wet granulation, leave residual moisture, which jeopardizes the stability of rosuvastatin and, consequently, of any pharmaceutical form manufactured with said methodology that contains it.

[019] As a consequence of the foregoing, efforts were made to eliminate the drawbacks related to the stability of pharmaceutical compositions comprising rosuvastatin and acetylsalicylic acid as active ingredients, developing a pharmaceutical composition comprising rosuvastatin and acetylsalicylic acid, a preparation process and uses thereof in which a single solid, stable, and immediate-release pharmaceutical form is provided. The proposed composition and its manufacturing process overcome the major drawbacks associated with the combination of active ingredients through its novel manufacturing process.

[020] Thus, the present invention proposes the combination in a single dosing unit of the active ingredients rosuvastatin and acetylsalicylic acid, solving a set of important technological challenges due to the physicochemical properties and the difference in dosages to ensure obtaining a stable product in the treatment and prevention of cardiovascular diseases. OBJECTIVES OF THE INVENTION

[021] Taking into account the shortcomings of the prior art, it is an objective of the present invention to provide a solid pharmaceutical composition. Petition 870250081794, dated 11 / 09 / 2025, page 21 / 86 9 / 50 comprising rosuvastatin and acetylsalicylic acid, wherein the said pharmaceutical composition is stable, immediate-release and easy to administer.

[022] Another objective of the invention is to provide a pharmaceutical composition comprising rosuvastatin and acetylsalicylic acid whose dissolution profile is comparable to that of the single drugs separately.

[023] A further objective of the invention is to provide a process for manufacturing a pharmaceutical composition comprising rosuvastatin and acetylsalicylic acid, improving the stability of the active ingredients.

[024] These and other objectives are achieved by means of a pharmaceutical composition comprising rosuvastatin and acetylsalicylic acid, preparation process and uses thereof according to the present invention. BRIEF DESCRIPTION OF THE INVENTION

[025] For this purpose, a first aspect of the present invention relates to a pharmaceutical composition comprising: a) a first phase comprising rosuvastatin; and b) a second phase comprising acetylsalicylic acid, wherein the first phase comprising rosuvastatin is a coated tablet and the second phase comprising acetylsalicylic acid is a granule. [0 26] In a second aspect of the invention, a manufacturing process for the pharmaceutical composition described above is provided, wherein the process comprises the steps of: a) to provide a first phase comprising rosuvastatin, wherein the first phase comprising rosuvastatin is a film-coated tablet; b) provide a second phase comprising acetylsalicylic acid, wherein the second phase comprising acetylsalicylic acid is a granule; and c) encapsulate the first phase comprising rosuvastatin and the second phase comprising acetylsalicylic acid. Petition 870250081794, dated 11 / 09 / 2025, page 22 / 86 10 / 50

[027] A third aspect of the invention relates to the use of the pharmaceutical composition of the present invention in the treatment of hyperlipidemia and in the prevention of at least one cardiovascular disease. BRIEF DESCRIPTION OF THE FIGURES

[028] The new aspects considered characteristic of the present invention will be set out in particular in the appended claims. However, some embodiments, features, and some objects and advantages thereof will be better understood from the detailed description when read in conjunction with the appended drawings, in which:

[029] Figure 1 is a flow diagram of a first stage of the process of preparing a pharmaceutical composition according to an embodiment of the invention.

[030] Figure 2 shows a flow diagram of a second and third stage of the process of preparing a pharmaceutical composition according to an embodiment of the invention.

[031] Figure 3 corresponds to the graph of the results of an accelerated stability study regarding the Rosuvastatin content of a pharmaceutical composition according to an embodiment of the invention.

[032] Figure 4 is a graphical representation of the results of an accelerated stability study with respect to the acetylsalicylic acid content of a pharmaceutical composition according to an embodiment of the invention.

[033] Figure 5 shows a graph of the results of an accelerated stability study regarding the dissolution of Rosuvastatin present in a pharmaceutical composition according to an embodiment of the invention.

[034] Figure 6 corresponds to the graph of the results of an accelerated stability study regarding the dissolution of acetylsalicylic acid present in a pharmaceutical composition according to an embodiment of the invention. Petition 870250081794, dated 11 / 09 / 2025, page 23 / 86 11 / 50

[035] Figure 7 shows a diagram of the comparative bioavailability study design.

[036] Figure 8 is an arithmetic scale profile of the mean plasma concentration of rosuvastatin as a function of time after drug administration.

[037] Figure 9 shows a semilogarithmic scale profile of the mean plasma concentration of rosuvastatin as a function of time after drug administration.

[038] Figure 10 shows an arithmetic scale profile of the mean plasma concentration of acetylsalicylic acid as a function of time after drug administration.

[039] Figure 11 is a semi-logarithmic scale profile of the mean plasma concentration of acetylsalicylic acid as a function of time after drug administration. DETAILED DESCRIPTION OF THE INVENTION

[040] It should be understood that the present invention is not limited to the methodologies, protocols and reagents provided by the detailed description, as these may vary. It should also be understood that the terminology used in this document is merely to describe particular embodiments and is not intended to limit the scope of this disclosure, which will be limited only by the appended claims. Unless otherwise defined, all technical and scientific terms used in this document have the same meaning as those commonly understood by a person skilled in the art. Definitions

[041] As used in the present invention, the term “approximately” refers to a measurable value that, due to the nature of the techniques employed to measure it, may vary. In the case of a quantity of Petition 870250081794, dated 11 / 09 / 2025, p. 24 / 86 12 / 50 weight, time, dosage, etc., it is understood that it covers, for example, variations of ± 20% or ± 10%, in another example ± 5%, in another example ± 1% and in another example ± 0.1% of the specified quantity, since such variations are appropriate to carry out the disclosed process.

[042] The term pharmaceutically acceptable salt of a given compound refers to salts that retain the biological efficacy and properties of the given compound and that are not biologically, or otherwise, undesirable. Pharmaceutically acceptable base addition salts may be prepared from inorganic or organic bases. Salts derived from inorganic bases include, by way of example only, sodium, potassium, lithium, ammonium, calcium, and magnesium salts.

[043] As used in the present invention, the term “stability” is defined as the ability of a pharmaceutical product to retain its chemical, physical, microbiological and biopharmaceutical properties within specified limits throughout its shelf life.

[044] The present invention relates to stable, immediate-release solid pharmaceutical compositions that maintain the dissolution and bioavailability of a statin and a nonsteroidal anti-inflammatory drug (NSAID). In particular, in the compositions of the present invention, the statin is rosuvastatin and the NSAID is acetylsalicylic acid. In this regard, it is known that the combination of rosuvastatin and acetylsalicylic acid presents a set of important technological challenges due to the physicochemical properties of the drugs, since the mixture of acetylsalicylic acid and rosuvastatin can result in the degradation of both active ingredients.

[045] In order to solve the technical problem described above, the present invention provides a pharmaceutical composition comprising: a) a first phase comprising rosuvastatin; and Petition 870250081794, dated 11 / 09 / 2025, page 25 / 86 13 / 50 b) a second phase comprising acetylsalicylic acid, wherein the first phase comprising rosuvastatin is a coated tablet and the second phase comprising acetylsalicylic acid is a granule.

[046] The pharmaceutical composition also comprises pharmaceutically acceptable excipients, which are selected from the group consisting of diluents, carriers, stabilizers, disintegrants, glidants, lubricants, coatings, binders, humectants and absorbents.

[047] Examples of pharmaceutically acceptable diluents include, but are not limited to, lactose monohydrate; cellulose derivatives, such as microcrystalline cellulose, silicified microcrystalline cellulose; starch derivatives, such as pregelatinized starch and corn starch; phosphates, such as dibasic calcium phosphate; mannitol, maltitol, dextrose, calcium phosphates or combinations thereof.

[048] In a non-limiting embodiment, pharmaceutically acceptable stabilizers are selected from the group consisting of anhydrous lactose, microcrystalline cellulose, starches, mannitol, maltitol, dextrose, calcium phosphates or combinations thereof.

[049] Pharmaceutically acceptable disintegrants include, but are not limited to, cellulose derivatives, for example, croscarmellose sodium, hydroxypropylcelluloses, carboxymethylcelluloses, microcrystalline cellulose; povidone derivatives, such as crospovidone, plasdones; starch derivatives, such as pregelatinized starch, sodium starch glycolate and corn starch; or combinations thereof.

[050] Examples of pharmaceutically acceptable glidants include cellulose derivatives, such as carboxymethylcellulose, microcrystalline cellulose; starch derivatives, for example, pregelatinized starch and corn starch; silicate derivatives, for example, magnesium silicate, trisilicate of Petition 870250081794, dated 11 / 09 / 2025, page 26 / 86 14 / 50 magnesium and talc.

[051] Examples of pharmaceutically acceptable lubricants include, but are not limited to, stearate derivatives, such as magnesium stearate, zinc stearate, calcium stearate, stearic acid, monostearates, stearyl fumarate; sulfate derivatives, such as magnesium lauryl sulfate and magnesium lauryl sulfate.

[052] With regard to the first phase which includes rosuvastatin, as previously indicated, it is available in the form of a coated tablet.

[053] The aforementioned rosuvastatin tablet further comprises at least one of a diluent, a stabilizing agent, a disintegrant, a glidant and a lubricant.

[054] In a non-limiting embodiment, the diluent is selected from the group consisting of lactose monohydrate; cellulose derivatives, including carboxymethylcellulose, mannitol, maltitol, dextrose, microcrystalline cellulose, anhydrous calcium phosphate, corn starch and combinations thereof. The stabilizing agent is selected from the group consisting of phosphate derivatives, including anhydrous dibasic calcium phosphate, aluminum and magnesium silicate, anhydrous lactose, microcrystalline cellulose, starches, mannitol, maltitol, dextrose and combinations thereof. The disintegrant is selected from the group consisting of croscarmellose sodium, cellulose derivatives including hydroxypropylcelluloses, carboxymethylcelluloses, microcrystalline cellulose; povidone derivatives including plasdones; starch derivatives including pregelatinized starch, sodium starch glycolate and corn starch.The glide is selected from the group consisting of colloidal silicon dioxide, cellulose derivatives, including carboxymethylcelluloses, microcrystalline cellulose, starch derivatives, including pregelatinized starch and corn starch, silicate derivatives, including magnesium silicate, magnesium trisilicate. Petition 870250081794, dated 11 / 09 / 2025, page 27 / 86 15 / 50 talc; and combinations thereof. The lubricant is selected from the group consisting of stearate derivatives, including zinc stearate, magnesium stearate, calcium stearate, stearic acid, monostearates, stearyl fumarate; sulfate derivatives, including magnesium lauryl sulfate and sodium lauryl sulfate; talc; and combinations thereof.

[055] As for the coating, it functions as a protective barrier between the active ingredients and as a moisture barrier, maintaining the stability of the composition. In a non-limiting embodiment, the coating is selected from the group consisting of cellulose derivatives, such as hydroxypropylmethylcellulose, hydroxypropylcellulose, carboxymethylcelluloses; polyvinyl derivatives, such as polyvinyl acetate; polyethylene glycol, povidone in all grades K and their derivatives. In one embodiment, the coating is polyvinyl acetate; in a preferred embodiment, the coating is opadry, such as, for example, opadry AMB II white 88A180021. To incorporate the coating, as described below, water is used as a solvent; however, it evaporates in the process. [ 056] In a more preferred embodiment, the first phase comprising rosuvastatin further comprises two lubricants, wherein the first lubricant is talc and the second lubricant is zinc stearate. [ 057] In an even more preferred embodiment, the first phase comprising rosuvastatin additionally comprises: - rosuvastatin or a pharmaceutically acceptable salt thereof as the active ingredient at a dosage of 10 mg to 20 mg of rosuvastatin; - Lactose monohydrate as a diluent in an amount of 40% to 80% by weight of the tablet; - Dibasic calcium phosphate as a stabilizing agent in an amount of 0.26% to 2% by weight of the tablet; Petition 870250081794, dated 11 / 09 / 2025, page 28 / 86 16 / 50 - Croscarmellose sodium as a disintegrant in an amount of 0.5% to 10% by weight of the tablet; - Colloidal silicon dioxide as a glidant in an amount of 0.08% to 2% by weight of the tablet; - talc as the primary lubricant in an amount of 0.5% to 10% by weight of the tablet; - Zinc stearate as a secondary lubricant in an amount of 0.5% to 10% by weight of the tablet; and - a polyvinyl acetate coating in an amount of 0.5% to 10% by weight of the tablet. [ 058] In a preferred embodiment, the rosuvastatin tablet comprises a dosage of 10 mg of rosuvastatin or a pharmaceutically acceptable salt thereof. [ 059] In another preferred embodiment, the rosuvastatin tablet comprises a dosage of 20 mg of rosuvastatin or a pharmaceutically acceptable salt thereof. [ 060] With regard to the pharmaceutically acceptable salt of rosuvastatin, in a preferred embodiment, rosuvastatin calcium is used. In this regard, a person skilled in the art will understand that adjustments must be made to the amount of rosuvastatin calcium used to obtain the desired dosage. [ 061] Based on the above, in a preferred embodiment, the rosuvastatin tablet is preferably in its calcium form, where 10.40 mg of rosuvastatin calcium is equivalent to a dosage of 10 mg of rosuvastatin. [ 062] In another preferred embodiment, rosuvastatin in tablet form is preferably in its calcium form, where 20.80 mg of rosuvastatin calcium is equivalent to a dosage of 20 mg of rosuvastatin. Petition 870250081794, dated 11 / 09 / 2025, page 29 / 86 17 / 50 [ 063] In a preferred embodiment, the amount of the active ingredient rosuvastatin is adjusted according to the titration. [ 064] In a preferred embodiment, the tablet coating is in an amount of 0.5% to 10% by weight of the tablet. [ 065] On the other hand, in a preferred embodiment, the second phase comprising acetylsalicylic acid and being a granulate which additionally comprises at least one of a diluent, a binder, a humectant, a glide and a lubricant.

[066] In a non-limiting embodiment, the binder is selected from the group consisting of glyceryl dibehenate; povidone and its derivatives; cellulose derivatives, including carbomers, hydroxypropylcellulose, carboxymethylcellulose; starch derivatives, including pregelatinized starch and corn starch; polyethylene glycol in its different grades; poloxamer; and combinations thereof. The humectant is selected from the group consisting of sodium lauryl sulfate; poloxamers; polyoxyethylene castor oil derivative; benzalkonium chloride; benzethonium chloride; polyoxyethylene alkyl ethers; polyoxyethylene sorbitan fatty acid esters; and combinations thereof.The slip agent is selected from the group consisting of colloidal silicon dioxide, cellulose derivatives, including carboxymethylcelluloses, microcrystalline cellulose, starch derivatives, including pregelatinized starch and corn starch, silicate derivatives, including magnesium silicate and magnesium trisilicate; talc; and combinations thereof. The lubricant is selected from the group consisting of stearate derivatives, including magnesium stearate, zinc stearate, calcium stearate, stearic acid, monostearates and stearyl fumarate; sulfate derivatives, including magnesium lauryl sulfate and sodium lauryl sulfate; talc; and combinations thereof. The diluent is selected from the... Petition 870250081794, dated 11 / 09 / 2025, page 30 / 86 18 / 50 group consisting of starch derivatives, including pregelatinized starch and corn starch; cellulose derivatives, including microcrystalline cellulose, carbomers, hydroxypropylcellulose and carboxymethylcellulose; polyethylene glycol in its different grades; poloxamer; and combinations thereof. [ 067] In a more preferred embodiment, the acetylsalicylic acid granules comprise two diluents, wherein the first diluent is pregelatinized starch and the second diluent is microcrystalline cellulose. [ 068] In an even more preferred embodiment, acetylsalicylic acid granules comprise: - Acetylsalicylic acid as the active ingredient in a dosage of 100 mg; - Pregelatinized starch as a primary diluent in an amount of 5% to 75% by weight of the granules; - Glyceryl dibehenate as a binder in an amount of 0.4% to 4% by weight of the granules; - Microcrystalline cellulose as a secondary diluent in an amount of 5% to 90% by weight of the granules; - Sodium lauryl sulfate as a humectant in an amount of 0.02% to 4% by weight of the granules; - Colloidal silicon dioxide as a glidant in an amount of 0.08% to 2% by weight of the granules; and - Zinc stearate as a lubricant in an amount of 0.1% to 1%.

[069] In a preferred embodiment, the acetylsalicylic acid granules comprise acetylsalicylic acid preferably in its free form. In this regard, a person skilled in the art will understand that adjustments must be made to the amount of acetylsalicylic acid to obtain the dosage. Petition 870250081794, dated 11 / 09 / 2025, page 31 / 86 19 / 50 equivalent desired, for example, quantities of 100 ± 0.5 mg can be used to obtain a dosage of 100 mg.

[070] In one embodiment, the pharmaceutical composition of the present invention is a solid form, preferably a capsule.

[071] The pharmaceutical composition as described above stands out for its physical, chemical and biological stability, as well as for the control of drug release and low cost.

[072] Surprisingly, the pharmaceutical composition of the present application was found to be highly stable, since, in a 6-month accelerated stability study, the pharmaceutical composition of the present invention was found to have retained its chemical and physical characteristics within the established specifications, maintaining its quality, efficacy and safety.

[073] Additionally, it was found that the bioavailability in humans of the active ingredients rosuvastatin and acetylsalicylic acid contained in the pharmaceutical composition of the present invention is comparable to the concomitant administration of the reference drugs, thus demonstrating the efficacy of the composition. Furthermore, the composition of the present invention is safe, since no serious adverse events were reported; in fact, the number of adverse events observed in a clinical study was greater for the concomitant administration of the single drugs.

[074] The pharmaceutical composition of the present invention is useful in the secondary prevention of cardiovascular events. In this sense, secondary prevention refers to reducing the risk of developing recurrent coronary artery and cerebrovascular disease, death or disability.

[075] Furthermore, there is evidence that the combination of acetylsalicylic acid and rosuvastatin is safe; moreover, it is an effective replacement therapy for monocomponent therapy in the secondary prevention of events. Petition 870250081794, dated 11 / 09 / 2025, page 32 / 86 20 / 50 secondary. The combined use of these medications is considered part of the comprehensive management of patients with cardiovascular disease in secondary prevention and is supported by numerous international guidelines, such as those of the American Heart Association and American College of Cardiology Foundation (AHA / ACCF) and the European Society of Cardiology (ESC). The magnitude of the benefit of the combination is associated with the anti-inflammatory properties of the drugs, which decrease cholesterol plaque, inflammation, platelet aggregation activation, and ultimately reduce cardiovascular events.

[076] As a consequence, the present invention also provides a method for the secondary prevention of cardiovascular events as a replacement therapy comprising the administration of a pharmaceutical composition according to the present invention, wherein the treatment is preferably intended for adult patients adequately controlled with the single-component drugs administered together in therapeutically equivalent dosages. Advantageously, the composition of the present invention provides better patient adherence to treatment as it reduces the number of dosages to be consumed while maintaining the efficacy of the concomitantly administered medications.

[077] Furthermore, considering that rosuvastatin is a lipid-lowering agent, the present invention also provides a method for treating hyperlipidemia and cardiovascular diseases. In a non-limiting embodiment, hyperlipidemia and cardiovascular disease are selected from the group consisting of hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia, hypertension, angina, infarctions, aneurysms, which comprises the administration of a pharmaceutical composition according to the present invention. In one embodiment, the pharmaceutical composition of the present invention participates in the regulation of blood concentration of Petition 870250081794, dated 11 / 09 / 2025, page 33 / 86 21 / 50 low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides, and cholesterol.

[078] In a preferred embodiment, the treatment method comprises administering a composition according to the present invention once a day.

[079] The present invention also describes an optimized process that allows the manufacture of a pharmaceutical composition as described above.

[080] The manufacturing process of the pharmaceutical composition as described comprises the following steps: a) To provide a first phase comprising rosuvastatin, wherein the first phase comprising rosuvastatin is a film-coated tablet; b) provide a second phase comprising acetylsalicylic acid, wherein the second phase comprising acetylsalicylic acid is a granule; and c) encapsulate the first phase comprising rosuvastatin and the second phase comprising acetylsalicylic acid. [ 081] The preparation of the first phase, which includes rosuvastatin, involves the following steps: - Mix rosuvastatin with a glidant, a disintegrant, a stabilizing agent, a diluent, and a first lubricant; - lubricate the previous mixture with at least one lubricant; - compress the lubricated mixture to obtain a rosuvastatin tablet; - Coat the tablet. [ 082] In a non-limiting embodiment, the diluent is lactose monohydrate, the stabilizing agent is dibasic calcium phosphate, the disintegrant is croscarmellose sodium, the glidant is colloidal silicon dioxide, Petition 870250081794, dated 11 / 09 / 2025, page 34 / 86 22 / 50 The solvent is purified water, the first lubricant is talc, the second lubricant is zinc stearate, and the coating is polyvinyl acetate. [ 083] Additionally, to incorporate the coating, it is dispersed in water, which evaporates in the process. [ 084] The second phase comprises acetylsalicylic acid, which corresponds to acetylsalicylic acid granules, wherein said granules do not have an enteric coating. [ 085] To prepare acetylsalicylic acid granules, the following steps are taken: - Mix acetylsalicylic acid with a humectant, a first diluent, and a binder; - granulate and heat the previous mixture; - Cool the mixture and add a glide and a second thinner; - Lubricate the mixture with a lubricant.

[086] In a non-limiting embodiment, the binder is glyceryl dibehenate, the humectant is lauryl sulfate, the glide is colloidal silicon dioxide, the lubricant is zinc stearate, the first diluent is pregelatinized starch and the second diluent is microcrystalline cellulose.

[087] In a preferred embodiment, the production of acetylsalicylic acid granules involves a melt granulation process employing a binding agent that is solid at room temperature but melts at relatively low temperatures. This binder can be added already melted to the preheated powder mixture or in solid form along with the other components of the mixture, so that granulation occurs in a single step by melting the binder within the mixture. After melting, the binding agent acts as a binding liquid for the powder particles, similar to the liquid added in wet processes. Petition 870250081794, dated 11 / 09 / 2025, page 35 / 86 23 / 50

[088] The melt granulation process avoids dust formation, eliminates the drying phase, making the granulation process shorter, and avoids the use of solvents and the potential problems that arise from them (hydrolysis of the active ingredient).

[089] In this particular case, melt granulation makes it possible to generate a protective barrier between the drugs and thus achieve their stability.

[090] Since glyceryl dibehenate has a melting point between 65°C and 85°C, the process requires a temperature of 85°C, the temperature at which the binder melts. Temperature control is critical, as it is a crucial factor in the drug's dissolution characteristics and granulation characteristics that ensure proper flow for the subsequent encapsulation step.

[091] Among the characteristics of acetylsalicylic acid are its high solubility, high permeability, and light sensitivity, characteristics that can be controlled with the granulation process using glyceryl dibehenate (binder), which, being hydrophobic, generates an isolation barrier that prevents interaction with rosuvastatin. In addition, the inclusion of the humectant sodium lauryl sulfate in the granulation process allows the generation of pores in the binder barrier, which ensure adequate dissolution of acetylsalicylic acid.

[092] On the other hand, the encapsulation step involves introducing the first phase comprising rosuvastatin and the second phase comprising acetylsalicylic acid into a gelatin capsule.

[093] Due to the innovation implemented in the drug's process and formulation, it was possible to obtain a product with demonstrably improved stability through studies in accordance with current standards, which met the quality attributes during the period. Petition 870250081794, dated 11 / 09 / 2025, page 36 / 86 24 / 50 evaluation. Stability tests are a means of comparing different formulations, packaging materials, or manufacturing processes in short-term experiments. Once the final formulation and definitive manufacturing process are established, the manufacturer conducts a series of stability tests that will allow them to predict the stability of the product or drug in this case and determine its shelf life and storage conditions.

[094] Initial and accelerated results for determining the stability of the compositions of the present invention, for the manufacture of a medicament useful in the treatment and prevention of cardiovascular diseases under conditions of 40 °C / 75%RH, are shown below in Example 2.

[095] Technological development comprised a series of evaluations that defined the formulation and process as described below. Those skilled in the art will discover that multiple variations and embodiments are possible in carrying out the present invention without departing from its spirit and scope to ensure proper product functioning and to meet the required quality characteristics.

[096] The present invention will be better understood from the following examples, which are presented for illustrative purposes only, to allow a complete understanding of the preferred embodiments of the present invention, without implying that there are no other embodiments not illustrated that can be put into practice based on the detailed description. EXAMPLES Example 1. Process for preparing a pharmaceutical composition according to an embodiment of the invention.

[097] Two pharmaceutical compositions comprising rosuvastatin and acetylsalicylic acid were manufactured, the first with a dosage of Petition 870250081794, dated 11 / 09 / 2025, page 37 / 86 The first dosage is 25 / 50 mg of rosuvastatin / 100 mg of acetylsalicylic acid, whose qualitative and quantitative formula is detailed in Table 1, and the second dosage is 20 mg of rosuvastatin / 100 mg of acetylsalicylic acid, whose qualitative and quantitative formula is detailed in Table 2. Table 1. Qualitative and quantitative formula of the pharmaceutical composition with a dosage of 10 mg of rosuvastatin / 100 mg of acetylsalicylic acid. Component Quantity Function Phase I Rosuvastatin calcium 10.40 mg Equivalent to 10.00 mg of rosuvastatin Active ingredient Lactose monohydrate 50.20 mg DCL 11 for adjustment of total solids to 73.00 mg / tablet Diluent Dibasic calcium phosphate 1.20 mg Anhydrous Stabilizing agent Croscarmellose sodium 3.50 mg Disintegrant Colloidal silicon dioxide 0.40 mg Glidant Talc 3.60 mg Lubricant Zinc stearate 0.70 mg Lubricant Coating Opardy 3.00 mg Opardy AMB II White 88A180021 Composition: Partially hydrolyzed polyvinyl alcohol........ 39.50% Talc...............................38.00% Titanium dioxide.............................15.00% GMCC type 1...........................................4.50% Sodium lauryl sulfate....................................3.00% Coating system Purified water csIt is evaporated during the process. Solvent Phase II Acetylsalicylic acid 100.00 mg Purity adjustment Active ingredient Pregelatinized starch 129.10 mg Diluent Glyceryl dibehenate 10.00 mg Binder Cellulose 50.00 mg pH 112 Diluent. Petition 870250081794, dated 11 / 09 / 2025, page 38 / 86 26 / 50 Component Quantity Microcrystalline Function For adjustment of total solids to 300.00 mg / capsule Lauryl sulfate 9.40 mg Humectant Colloidal silicon dioxide 0.75 mg Glidant Zinc stearate 0.75 mg Lubricant Table 2. Qualitative and quantitative formula of the pharmaceutical composition with a dosage of 20 mg of rosuvastatin / 100 mg of acetylsalicylic acid. Component Quantity Function Phase I Rosuvastatin calcium 20.80 mg Equivalent to 20.00 mg of rosuvastatin Active ingredient Lactose monohydrate 39.80 mg DCL 11 for adjustment of total solids to 73.00 mg / tablet Diluent Dibasic calcium phosphate 1.20 mg Anhydrous Stabilizing agent Croscarmellose sodium 3.50 mg Disintegrant Colloidal silicon dioxide 0.40 mg Glidant Talc 3.60 mg Lubricant Zinc stearate 0.70 mg Lubricant Coating Opardy 3.00 mg Opardy AMB II White 88A180021 Composition: Partially hydrolyzed polyvinyl alcohol.........39.50% Talc...................................38.00% Titanium dioxide...............................15.00% GMCC type 1.............................................4.50% Sodium lauryl sulfate....................................3.00% Coating system Purified water csIt is evaporated during the process. Solvent Phase II Acetylsalicylic acid 100.00 mg Purity adjustment Active ingredient Pregelatinized starch 129.10 mg Diluent Glyceryl dibehenate 10.00 mg Binder. Petition 870250081794, dated 11 / 09 / 2025, page 39 / 86 27 / 50 Component Quantity Function Microcrystalline cellulose 50.00 mg pH 112 For adjustment of total solids to 300.00 mg / capsule Diluent Lauryl sulfate 9.40 mg Humectant Colloidal silicon dioxide 0.75 mg Glidant Zinc stearate 0.75 mg Lubricant

[098] To prepare the pharmaceutical compositions according to an embodiment of the present invention, as described above, a process was carried out which generally consists of three steps described below: I. Development of a first phase comprising rosuvastatin: The objective of this stage is to develop a first phase that includes rosuvastatin, for which the following steps were followed: 1. Rosuvastatin calcium (active ingredient) was mixed with a glidant (colloidal silicon dioxide), a disintegrant (croscarmellose sodium), and a stabilizing agent (anhydrous dibasic calcium phosphate) for approximately 8 minutes. The excipients were previously sieved. [09 9] 2. A sieving operation was carried out using a 0.045 inch (1.143 mm) mesh on mixture 2.

[100] 3. The sieving from step no. 2 was mixed with a diluent (lactose monohydrate DCL 11) for approximately 5 minutes.

[101] 4. The mixture from step no. 3 was mixed with a first lubricant (talc) that had been previously sifted for approximately 03 minutes.

[102] 5. The mixture from step no. 4 was mixed with a second lubricant (zinc stearate) for approximately 3 minutes.

[103] 6. The lubricated mixture obtained in step no. 5 was compressed into cores of 70 ± 7.0 mg, with a hardness of 3.0 - 8.0 kp and a disintegration time of less than 5 minutes.

[104] 7. The cores obtained in step 6 were coated with a Petition 870250081794, dated 11 / 09 / 2025, page 40 / 86 28 / 50 polyvinyl acetate coating, which is Opadry AMB II white 88A180021, which has been previously dispersed in water.

[105] The result of the development of the previous steps is a white, biconvex coated tablet, smooth on both faces, with an average weight of 73.0 mg ± 7.0 mg; a thickness of 3.0 mm to 3.6 mm; and a disintegration time not exceeding 5 min in water at 37 °C ± 2 °C.

[106] II. Development of a second phase comprising acetylsalicylic acid: The objective of this stage is to develop a second phase that includes acetylsalicylic acid, for which the following steps were followed: 1. Acetylsalicylic acid (active ingredient), a humectant (sodium lauryl sulfate), a portion (approximately 38.7%) of the first diluent (pregelatinized starch), and a binder (glyceryl dibehenate) were mixed for approximately 3 minutes in a granulator.

[107] 2. The granulator equipment was heated for approximately 15 min at a temperature of approximately 85 °C.

[108] 3. A granulation process was carried out until a temperature between approximately 65 °C and 70 °C was reached.

[109] 4. The remainder (approximately 61.3%) of the first diluent (pregelatinized starch) was added.

[110] 5. The granulator equipment was cooled to a temperature between approximately 30°C and 35°C.

[111] 6. A reduction in particle size was achieved by sieving the granules from step no. 5 through a 0.050 inch mesh.

[112] 7. A slip agent (colloidal silicon dioxide) and a second diluent (microcrystalline cellulose PH112) were added and mixed for approximately 5 minutes. Petition 870250081794, dated 11 / 09 / 2025, page 41 / 86 29 / 50

[113] 8. A lubricant (zinc stearate) was added and mixed for approximately 3 minutes.

[114] III. Encapsulation

[115] For encapsulation and therefore preparation of a pharmaceutical composition according to the present invention, a capsule number 0 was used, which has an opaque white body and an opaque red cap, for this purpose, phase I comprising rosuvastatin and phase II comprising acetylsalicylic acid were introduced into said gelatin capsule.

[116] The average weight of the capsule (capsule + powder) was 396.0 mg ± 30.0 mg; the average weight of the contents (granules + tablet) was 373.0 mg ± 30.0 mg; the average weight of the filled capsule was 469.0 mg ± 30.0 mg; the disintegration time was less than 15 min in water at 37 °C ± 2.0 °C.

[117] Finally, the pharmaceutical composition was packaged in primary packaging consisting of a cold-formed aluminum foil blister of 176 µm - 25 µm aluminum foil which provides airtightness; the secondary packaging is a white cardboard box.

[118] The detailed process is described in Figures 1 and 2. In particular, Figure 1 corresponds to the flow diagram of Stage I of production of the first phase comprising rosuvastatin, while Figure 2 is a flow diagram of Stages II and III, i.e., the elaboration of the second phase comprising acetylsalicylic acid and encapsulation. Example 2. Stability of a pharmaceutical composition according to a preferred embodiment of the present invention.

[119] The objective of the stability study was to evaluate the stability of a pharmaceutical composition according to a preferred embodiment of the present invention, particularly of a composition as described in Example 1, Table 1 (dosage of 10 mg rosuvastatin / 100 mg acid) Petition 870250081794, dated 11 / 09 / 2025, page 42 / 86 30 / 50 acetylsalicylic acid) under accelerated stability conditions (40 °C ± 2 °C / 75% ± 2% relative humidity) for 6 months.

[120] The study began on July 30, 2021 and was completed on January 30, 2022, in accordance with section 11 of the Mexican Official Standard NOM-059-SSA1-2015, Good manufacturing practices for medicines, and in accordance with section 7.1 of NOM-073-SSA1-2015, Stability of Drugs and Medicines, as well as herbal remedies.

[121] During the study, three batches (DFF2106-17, DFF2106-18 and DFF2106-19) of the pharmaceutical composition described in Table 1 (dosage of 10 mg rosuvastatin / 100 mg acetylsalicylic acid) were evaluated and packaged in a primary packaging consisting of a cold-formed foil blister 176 µm - foil 25 µm; the secondary packaging is a white cardboard box.

[122] Initial sampling was carried out at the end of the first month (August 30, 2021), the third month (October 30, 2021), and at six months (January 30, 2022). The following samples were considered for each analysis period: - 40 blisters for physicochemical tests.

[123] - 32 blisters for microbiological tests for the initial and final periods.

[124] The parameters analyzed were product description, rosuvastatin content, acetylsalicylic acid content, rosuvastatin dissolution, acetylsalicylic acid dissolution, rosuvastatin organic impurities, salicylic acid limit, microbial limits (initial and final period) and water content (tablet and granules).

[125] The results obtained for the three lots evaluated can be found in Tables 3, 4 and 5. Petition 870250081794, dated 11 / 09 / 2025, page 43 / 86 Table 3. Stability study results for batch DFF2106-17 Determination Specification Sample No. Initial 30-Jul-2021 1 month 30-Aug-2021 3 months 30-Oct-2021 6 months 30-Jan-2022 Rosuvastatin Content Rosuvastatin 90.0% to 110.0% M1 97.25% 98.22% 95.99% 96.42% M2 98.01% 94.61% 95.67% 96.47% M3 97.23% 97.70% 95.57% 96.43% Average 97.5% 97.8% 95.7% 96.4% CV 0.46% 0.34% 0.23% 0.02% Rosuvastatin 10.0 mg / capsule M1 9.73 9.82 9.60 9.64 M2 9.80 9.76 9.57 9.65 M3 9.72 9.77 9.56 9.64 Maverage 9.8 9.8 9.6 9.6 Content Acetylsalicylic acid Acetylsalicylic acid 90.0% to 110.0% M1 107.03% 105.89% 102.27% 97.30% M2 106.48% 106.03% 102.08% 97.32% M3 106.58% 105.94% 101.93% 97.17% Average 106.7% 106.0% 102.1% 97.3% CV 0.27% 0.07% 0.16% 0.08% Acetylsalicylic acid 100.0 mg / capsule M1 107.03 105.89 102.27 97.30 M2 106.48 106.03 102.08 97.32 M3 106.58 105.94 101.93 97.17 Average 106.7 106.0 102.1 97.3 Rosuvastatin Dissolution Rosuvastatin Q = 75.0% in 30 minutes M1 97.72% 91.60% 95.59% 93.25% M2 102.24% 94.00% 89.72% 90.61% M3 99.52% 101.35% 98.60% 83.32% M4 96.52% 96,40% 95.80% 96.39% 31 / 50 Petition 870250081794, dated 11 / 09 / 2025, p. 44 / 86 Determination Specification Sample No. Initial 30-Jul-2021 1 month 30-Aug-2021 3 months 30-Oct-2021 6 months 30-Jan-2022 M5 97.68% 101.53% 98.39% 93.43% M6 96.76% 96.21% 103.75% 99.46% Average 98.4% 96.9% 97.8% 92.7% CV 2.19% 4.09% 4.46% 5.96% Dissolution Acetylsalicylic acid Acetylsalicylic acid Q = 70.0% in 45 minutes M1 103.43% 93.79% 89.52% 79.72% M2 93.74% 91.51% 92.65% 81.79% M3 102.27% 86.88% 91.73% 76.08% M4 99.08% 89.42% 85.11% 85.36% M5 101.78% 85.34% 93.07% 77.18% M6 95.53% 88.32% 94.35% 83.16% Average 99.3% 89.2% 91.1% 80.6% CV 3.96% 3.46% 3.66% 4.42% Organic impurities Rosuvastatin Rosuvastatin ketone: Not more than 2.10% M1 0.15% 0.25% 0.27% Rosuvastatin lactone: Not more than 3.80% M1 0.09% 0.27% 0.54% 3.47% Rosuvastatin ethyl ester: Not more than 0.50% M1 Not detected Not detected Not detected Not detected Any non-specific degradation product: No M1 0.03% 0.04% 0.01% 0.03% 32 / 50 Petition 870250081794, dated 11 / 09 / 2025, page 45 / 86 Determination Specification Sample No. Initial 30-Jul-2021 1 month 30-Aug-2021 3 months 30-Oct-2021 6 months 30-Jan-2022 more than 0.20% Total degradation products: Not more than 3.60% M1 0.09% 0.08% 0.06% 0.18% Salicylic acid limit Not more than 2.00% X20 0.28% 0.39% 0.38% 1.56% Microbial limits Aerobic mesophilic count: Not more than 10³ CFU / g X20 Less than 10 CFU / g Not applicable Less than 10 CFU / g Less than 10 CFU / g Filamentous fungi and yeasts: Not more than 10² CFU / g Less than 10 CFU / g Not applicable Less than 10 CFU / g Less than 10 CFU / g Absence of pathogens: Absence of Escherichia coli Absence of Escherichia coli Not applicable Absence of Escherichia coli Absence of Escherichia coli Water content Tablet: Not more than 15.00% x 20 4.55% 4.67% 4.77% 3.98% Granules: No 4.16% 4.33% 4.11% 2.93% 33 / 50 Petition 870250081794, dated 11 / 09 / 2025, page 46 / 86 Determination Specification Sample No. Initial 30-Jul-2021 1 month 30-Aug-2021 3 months 30-Oct-2021 6 months 30-Jan-2022 more than 15.00% Table 4. Stability study results for batch DFF2106-18 Determination Specification Sample No. Initial 30-Jul-2021 1 month 30-Aug-2021 3 months 30-Oct-2021 6 months 30-Jan-2022 Rosuvastatin Content Rosuvastatin 90.0% to 110.0% M1 98.06% 95.40% 97.45% 97.53% M2 98.59% 96.57% 97.36% 97.48% M3 98.09% 96.17% 97.25% 97.58% Average 98.3% 96.1% 97.4% 97.5% CV 0.30% 0.62% 0.10% 0.05% Rosuvastatin 10.0 mg / capsule M1 9.81 9.54 9.75 9.75 M2 9.86 9.66 9.74 9.75 M3 9.81 9.62 9.73 9.76 Maverage 9.8 9.6 9.7 9.8 Content Acetylsalicylic acid Acetylsalicylic acid 90.0% to 110.0% M1 105.00% 101.93% 102.55% 97.10% M2 106.80% 102.45% 103.02% 97.11% M3 103.55% 102.36% 102.53% 97.12% Average 105.1% 102.3% 102.7% 97.1% CV 1.55% 0.27% 0.27% 0.01% Acetylsalicylic acid 100.0 mg / capsule M1 105.00 101.93 102.55 97.10 M2 106.80 102.45 103.02 97.11 M3 103.55 102.36 102.53 97.12 Average 105.1 102.3 102.7 97.1 Rosuvastatin Dissolution M1 95.25% 94.86% 92.74% 90.55% 34 / 50 Petition 870250081794, dated 11 / 09 / 2025, page 47 / 86 Determination Specification Sample No. Initial 30-Jul-2021 1 month 30-Aug-2021 3 months 30-Oct-2021 6 months 30-Jan-2022 Rosuvastatin Q = 75.0% in 30 minutes M2 98.07% 95.89% 93.02% 94.51% M3 96.54% 100.67% 96.14% 92.49% M4 100.61% 98.93% 96.70% 100.52% M5 100.70% 100.83% 101.18% 95.08% M6 97.59% 100.89% 98.83% 93.70% Average 98.1% 98.7% 96.4% 94.5% CV 2.23% 2.71% 3.40% 3.57% Dissolution Acetylsalicylic acid Acetylsalicylic acid Q = 70.0% in 45 minutes M1 82.23% 90.94% 93.24% 82.94% M2 82.78% 94.56% 90.27% 79.71% M3 96.22% 89.99% 87.68% 85.33% M4 89.64% 94.39% 79.32% 88.94% M5 83.82% 89.16% 90.81% 86.94% M6 79.19% 91.63% 87.38% 82.04% Average 85.7% 91.8% 88.1% 84.3% CV 7.25% 2.45% 5.47% 4.02% Organic impurities Rosuvastatin Rosuvastatin ketone: Not more than 2.10% M1 0.16% 0.23% 0.31% 0.44% Rosuvastatin lactone: Not more than 3.80% M1 0.09% 0.27% 0.51% 3.10% Rosuvastatin ethyl ester: Not detected M1 Not detected Not detected Not detected Not detected 35 / 50 Petition 870250081794, dated 11 / 09 / 2025, page 48 / 86 Determination Specification Sample No. Initial 30-Jul-2021 1 month 30-Aug-2021 3 months 30-Oct-2021 6 months 30-Jan-2022 more than 0.50% Any non-specific degradation product: Not more than 0.20% M1 0.04% 0.03% 0.01% 0.03% Total degradation products: Not more than 3.60% M1 0.10% 0.07% 0.06% 0.16% Salicylic acid limit Not more than 2.00% X20 0.26% 0.37% 0.36% 1.51% Microbial limits Aerobic mesophilic count: Not more than 103 CFU / g X20 Less than 10 CFU / g Not applicable Less than 10 CFU / g Less than 10 CFU / g Filamentous fungi and yeasts: Not more than 10² CFU / g Less than 10 CFU / g Not applicable Less than 10 CFU / g Less than 10 CFU / g Absence of pathogens: Absence of Escherichia coli Not applicable Absence of Escherichia coli Absence of Escherichia coli 36 / 50 Petition 870250081794, dated 11 / 09 / 2025, page 49 / 86 Determination Specification Sample No. Initial 30-Jul-2021 1 month 30-Aug-2021 3 months 30-Oct-2021 6 months 30-Jan-2022 Escherichia coli Water content Tablet: Not more than 15.00% X20 4.54% 4.76% 4.87% 4.31% Granules: Not more than 15.00% 3.95% 4.21% 4.24% 3.08% Table 5. Stability study results for batch DFF2106-19 Determination Specification Sample No. Initial 30-Jul-2021 1 month 30-Aug-2021 3 months 30-Oct-2021 6 months 30-Jan-2022 Rosuvastatin Content Rosuvastatin 90.0% to 110.0% M1 98.20% 98.37% 96.72% 96.98% M2 98.48% 98.43% 96.72% 97.13% M3 98.30% 97.44% 96.86% 97.11% Average 98.3% 98.1% 96.8% 97.1% CV 0.14% 0.57% 0.09% 0.08% Rosuvastatin 10.0 mg / capsule M1 9.82 9.84 9.67 9.70 M2 9.85 9.84 9.67 9.71 M3 9.83 9.74 9.69 9.71 Maverage 9.8 9.8 9.7 9.7 Content Acetylsalicylic acid Acetylsalicylic acid 90.0% to 110.0% M1 105.34% 103.94% 104.76% 96.63% M2 105.25% 104.39% 104.89% 96.40% M3 104.96% 104.53% 105.10% 96.56% Average 105.2% 104.3% 104.9% 96.5% CV 0.19% 0.29% 0.16% 0.12% M1 Acid 105.34 103.94 104.76 96.63 37 / 50 Petition 870250081794, dated 11 / 09 / 2025, page 50 / 86 Determination Specification Sample No. Initial 30-Jul-2021 1 month 30-Aug-2021 3 months 30-Oct-2021 6 months 30-Jan-2022 Acetylsalicylic acid 100.0 mg / capsule M2 105.25 104.39 104.89 96.40 M3 104.96 104.53 105.10 96.56 Average 105.2 104.3 104.9 96.5 Rosuvastatin Dissolution Rosuvastatin Q = 75.0% in 30 minutes M1 97.46% 97.62% 96.31% 91.25% M2 104.73% 99.91% 95.69% 97.86% M3 96.45% 98.38% 101.26% 94.60% M4 98.31% 95.24% 101.75% 93.96% M5 101.13% 99.46% 86.86% 92.59% M6 99.74% 97.23% 98.65% 97.20% Average 99.6% 98.0% 98.4% 94.6% CV 3.01% 1.73% 2.63% 2.72% Dissolution Acetylsalicylic acid Acetylsalicylic acid Q = 70.0% in 45 minutes M1 84.05% 82.37% 80.54% 95.15% M2 86.60% 83.01% 83.42% 100.32% M3 90.98% 81.90% 89.24% 93.23% M4 93.02% 84.35% 80.05% 93.78% M5 95.61% 83.71% 90.77% 95.76% M6 82.89% 88.44% 92.49% 90.51% Average 88.9% 84.0% 86.1% 94.8% CV 5.77% 2.81% 6.30% 3.45% Organic impurities Rosuvastatin Rosuvastatin ketone: Not more than 2.10% M1 0.16% 0.22% 0.27% 0.43% Rosuvastatin M1 0,10% 0.24% 0.53% 2.68% 38 / 50 Petition 870250081794, dated 11 / 09 / 2025, page 51 / 86 Determination Specification Sample No. Initial 30-Jul-2021 1 month 30-Aug-2021 3 months 30-Oct-2021 6 months 30-Jan-2022 Lactone: Not more than 3.80% Rosuvastatin ethyl ester: Not more than 0.50% M1 Not detected Not detected Not detected Not detected Any non-specific degradation product: Not more than 0.20% M1 0.03% 0.03% 0.01%. 0.03% Total degradation products: Not more than 3.60% M1 0.08% 0.07% 0.06% 0.15% Salicylic acid limit Not more than 2.00% X20 0.28% 0.39% 0.48% 1.53% Microbial limits Aerobic mesophilic count: Not more than 10³ CFU / g X20 Less than 10 CFU / g Not applicable Less than 10 CFU / g Less than 10 CFU / g Filamentous fungi and yeasts: Not more than 10² Less than 10 CFU / g Not applicable Less than 10 CFU / g Less than 10 CFU / g 39 / 50 Petition 870250081794, dated 11 / 09 / 2025, page 52 / 86 Determination Specification Sample No. Initial 30-Jul-2021 1 month 30-Aug-2021 3 months 30-Oct-2021 6 months 30-Jan-2022 CFU / g Absence of pathogens: Absence of Escherichia coli Absence of Escherichia coli Not applicable Absence of Escherichia coli Absence of Escherichia coli Water content Tablet: Not more than 15.00% X20 4.64% 4.64% 5.15% 4.72% Granules: Not more than 15.00% 3.40% 4.04% 4.29% 2.66% 40 / 50 Petition 870250081794, dated 11 / 09 / 2025, page 53 / 86 41 / 50

[126] Regarding the product description, the evaluated batches met the specification in all analysis periods, that is, the product description corresponded to a capsule no. 0 opaque white body and opaque red cap containing a biconvex coated tablet of white color, smooth on both faces and granulated of white color free of foreign particles.

[127] Figure 2 is a graph of the Rosuvastatin content results for the three batches tested. It is appreciated that the rosuvastatin content underwent small modifications throughout the study, but the general trend is to maintain the content within the specification.

[128] Similarly, Figure 3 is a graphical representation of the Acetylsalicylic Acid content results for the three batches evaluated. It is appreciated that the Acetylsalicylic Acid content underwent small modifications throughout the study, but the general trend is to maintain the content within the specification.

[129] On the other hand, Figure 4 shows the dissolution results of rosuvastatin. It can be observed that, for all three batches evaluated, the dissolution of rosuvastatin decreased slightly at the end of the study; however, despite this decrease, the percentage of rosuvastatin dissolved remains higher than the specification.

[130] Regarding the dissolution of acetylsalicylic acid (Figure 5), there was greater variation in the results between batches, however the percentage of acetylsalicylic acid was greater than 70.0% in the periods evaluated and in all batches, so the specification was met.

[131] Based on the results presented and described above, it is clear that the evaluated batches (DFF2106-17, DFF2106-18 and DFF2106-19) demonstrated that they maintain their chemical and physical characteristics within the established specifications, thus guaranteeing their quality, effectiveness and safety. Petition 870250081794, dated 11 / 09 / 2025, page 54 / 86 42 / 50 Example 3. Comparative bioavailability study

[132] A comparative bioavailability study was conducted in humans to evaluate differences in the magnitude and rate of absorption between a pharmaceutical composition according to a preferred embodiment of the present invention and the concomitant administration of the reference drugs. The secondary objective of the study was to evaluate the safety and tolerability of a composition according to a preferred embodiment of the present invention in healthy male and female subjects under fasting conditions.

[133] For this purpose, as illustrated in Figure 6, a single-center, longitudinal, prospective, open-label, crossover, randomized study was conducted with two treatments, two periods, two sequences with a single dose of a capsule of the pharmaceutical composition according to a preferred embodiment of the present invention (test drug) and a tablet of both reference drugs (according to the randomization sequence), under fasting conditions, with 250 mL of water and a 7-day washout period between each dose of the research product.

[134] The reference medicines were as follows: - Crestor®: Tablet containing 10 mg of Rosuvastatin from AstraZeneca, SA de CV

[135] - Aspirin Junior®: Tablet containing 100 mg of acetylsalicylic acid from Bayer de México, SA de CV

[136] As indicated above, the test drug corresponds to a pharmaceutical composition according to an embodiment of the present invention, particularly a pharmaceutical composition as described in Example 1 and Table 1.

[137] The clinical study was evaluated and approved by the Ethics Committee in Petition 870250081794, dated 11 / 09 / 2025, page 55 / 86 43 / 50 Research was conducted by the Research Committee of AvantSanté Research Center, SA de CV. Subsequently, it was evaluated and authorized by the Federal Commission for Protection against Sanitary Risks (COFEPRIS) under procedure number 213301410B0347 / 2021.

[138] Before any process related to the clinical study, the research individuals signed the Free and Informed Consent Form after receiving complete written and verbal information about the aspects involved in the study, thus corroborating their voluntary participation.

[139] The study consisted of two hospitalization periods. In each period, volunteers remained in the clinical unit facilities for approximately 36 hours (12 hours before and 24 hours after dosing the products under investigation), in order to standardize the individuals' diet and evaluate the safety of the products. The study periods were separated by a 7-day washout period.

[140] Twenty-six samples (in each period) of 8 mL of whole blood each were collected at the following times: 0.0, 0.167, 0.25, 0.34, 0.50, 0.75, 01.00, 01.25, 01.50, 01.75, 02.00, 02.50, 03.00, 03.50, 04.00, 04.50, 05.00, 06.00, 08.00, 10.00, 12.00, 16.00, 24.00, 36.00, 48.00 and 72.00 hours after the assay with the products under investigation. Samples were collected in 8 mL vacutainer tubes containing K2EDTA (dipotassium ethylenediaminetetraacetic acid) as an anticoagulant. There was a 2-minute phase-out interval between each study group. Rosuvastatin and salicylic acid (a metabolite of acetylsalicylic acid) were quantified by reversed-phase Ultra High Resolution Liquid Chromatography coupled to a Mass-Mass detector. Population

[141] Thirty-six research individuals were included in the clinical study, of whom 21 were men and 15 were women, with ages ranging from 19 to 50 Petition 870250081794, dated 11 / 09 / 2025, pp. 56 / 86 44 / 50 years old, with an average age of 29 years.

[142] During the first study period, individual 03 was removed from the study due to an adverse event (COVID-19), which was not related to the treatment. During the second study period, individuals 32 and 33 were removed from the study due to withdrawal of informed consent. As mentioned earlier, 33 of the 36 research individuals completed their participation in the clinical study. Treatment administered

[143] Table 6 shows the characteristics of the treatments administered. Table 6. Treatments administered, description of medications. Drug Details Trial drug (A) Reference drug (B1) Reference drug (B2) International generic name Rosuvastatin / Acetylsalicylic acid Rosuvastatin Acetylsalicylic acid Distinctive name N / A CRESTOR® ASPIRIN JUNIOR® Pharmaceutical form Capsules Tablets Tablets Dosage 10 mg / 100 mg 10 mg 100 mg Concentration 10 mg / 100 mg 10 mg 100 mg Dosages administered 35 34 34 Vital signs

[144] Vital signs, including blood pressure, respiratory rate, heart rate and temperature, were measured at admission, before dosing, at 1:00 and 3:00 (within a range of ±45 minutes) after dosing and before discharge in each study period. Adverse events

[145] During the conduct of the study, a total of 4 adverse events occurred: 2 Headache, 1 COVID-19 and 1 decrease in blood pressure Petition 870250081794, dated 11 / 09 / 2025, page 57 / 86 45 / 50 systolic. According to the severity of the event, 3 events were classified as “mild” and 1 as “moderate”. Based on causality, 2 events were classified as probable, 1 as possible, and 1 as improbable; regarding the assessment of safety issues, 2 events were considered expected and 2 as unexpected. According to the established authorized clinical protocol and the current NOM-220-SSA1-2016 “Installation and operation of pharmacovigilance”, all adverse events were classified as non-serious and unrelated to treatment. Table 7 describes the adverse events that occurred. Petition 870250081794, dated 11 / 09 / 2025, pp. 58 / 86 Table 7. Description of adverse events Individual Number Treatment Administered Patient Gender Patient Age (years) Severity of Notification Adverse Event Reported Severity Casualty Expected or Unexpected Event 26 Reference Medication (B1 and B2) Male 24 Non-severe Headache Moderate Possible Expected 03 Reference Medication (B1 and B2) Male 22 Non-severe COVID-19 Mild Unlikely Unexpected 05 Reference Medication (B1 and B2) Male 24 Non-severe Decrease in systolic blood pressure Mild Possible Unexpected 17 Reference Medication (B1 and B2) Male 50 Non-severe Headache Mild Possible Expected 46 / 50 Petition 870250081794, dated 11 / 09 / 2025, page 59 / 86 47 / 50 Pharmacokinetic bioavailability between treatments

[146] To determine that the test drug (A) has a similar comparative bioavailability with concomitant administration of the reference drugs Bi and B2, it had to be met that the confidence intervals of the geometric means of the quotient (test / reference) of the maximum observed plasma concentration (Cmax) and ABC parameters of rosuvastatin and salicylic acid (acetylsalicylic acid metabolite) were between 80% and 125% and the Schuirmann one-sided double t-test showed a value less than 0.05.

[147] The results of the comparative bioavailability are shown in Tables 8 and 9. Table 8. Pharmacokinetic parameters of administered medications Parameter A Bi + B2 Rosuvastatin Salicylic acid Rosuvastatin Salicylic acid Cmax (ng / mL) 7.892 ± 4.6560 7359.168 ± 1485.6889 7.162 ± 4.2202 7352.475 ± 1669.0617 AUC0-t 72.467 ± 28939.434 ± 68.085 ± 28981.949 ± (h*ng / mL) 40.0741 7336.1749 40.9434 8143.0935 AUC0-inf 75.484 ± 30250.490 ± 71.446 ± 30295.059 ± (h(ng / mL) 40.1511 7247.0982 40.7350 8295.9829 tmax (h) 4.288 ± 0.9273 1.508 ± 0.5247 3.924 ± 1.2382 1.833 ± 0.8585 Kel (1 / h) 0.047 ± 0.0150 0.379 ± 0.0802 0.048 ± 0.0221 0.376 ± 0.0719 t1 / 2 16.585 ± 1.907 ± 17.376 ± 1.922 ± (h) 6.6856 0.3915 9.0628 0.4409 Petition 870250081794, dated 11 / 09 / 2025, pp. 60 / 86 Table 9. Results of statistical bioavailability assays between medications with data transformed to their natural logarithm. Parameter A / B (%) Least squares geometric mean Schuirmann confidence interval Statistical power (%) AB (80.00 125.00%) P < 80.00 P > 125.00 Rosuvastatin Cmax 109.7 6.848 6.244 98.28 122.39 0.000 0 0.0260 95.5 Lactic acid AUCo-4 107.0 63.672 59.495 97.56 117.39 0.000 0 0.0039 98.9 Salicylic acid Cmax 100.7 7198.8 63 7146.769 93.97 107.97 0.000 0 0.0000 100.0 AUCo-4 100.4 28002, 313 27902,361 95.95 104.97 0.000 0 0.0000 100.0 48 / 50 Petition 870250081794, dated 11 / 09 / 2025, pp. 61 / 86 49 / 50

[148] Figures 8 and 9 show the pharmacokinetic profile of the maximum concentration of treatment A (pharmaceutical composition according to an embodiment of the present invention) and the concomitant administration of the reference drugs Bi and B2.

[149] Figures 10 and 11 correspond to the pharmacokinetic profile of the maximum concentration of treatment A (pharmaceutical composition according to an embodiment of the present invention) and the concomitant administration of reference drugs B1 and B2 on a normal and semilogarithmic scale for salicylic acid.

[150] Statistical analysis between test drug A (pharmaceutical composition according to an embodiment of the present invention) and reference drugs B1 and B2 demonstrated that the pharmacokinetic parameters of observed maximum plasma concentration (Cmax) and area under the plasma concentration curve from time zero to the last measurable concentration (AUC0-t) are directly related and without statistically significant differences in the rate of absorption and amount of drug absorbed, and the confidence intervals of the pharmacokinetic parameters described above are within the ranges of 80%-125% for transformed data of Rosuvastatin / Salicylic Acid. As a consequence, the bioavailability of test product A (pharmaceutical composition according to an embodiment of the present invention) is comparable with reference drugs B1 and B2.

[151] As described above, it can be observed that the pharmaceutical composition comprising rosuvastatin and acetylsalicylic acid was designed to provide a stable, immediate-release pharmaceutical form that has a bioavailability of the active ingredients similar to that of concomitantly administered monodrugs, and will be evident to Petition 870250081794, dated 11 / 09 / 2025, pp. 62 / 86 50 / 50 any person skilled in the art that the embodiments of the pharmaceutical composition comprising rosuvastatin and acetylsalicylic acid, the preparation process and uses thereof, as described above and illustrated in the accompanying drawings, are merely illustrative, but not limiting, of the present invention, since numerous significant alterations in its details are possible without departing from the scope of the invention.

[152] Therefore, the present invention should not be considered restricted, except as required by the state of the art and the scope of the appended claims. Petition 870250081794, dated 11 / 09 / 2025, pp. 63 / 86

Claims

1 / 9 CLAIMS 1. Pharmaceutical composition, characterized in that it comprises: (a) a first phase comprising rosuvastatin and (b) a second phase comprising acetylsalicylic acid, wherein the first phase comprising rosuvastatin is a coated tablet and the second phase comprising acetylsalicylic acid is a granule.

2. Pharmaceutical composition, according to claim 1, characterized in that it further comprises pharmaceutically acceptable excipients selected from the group consisting of diluents, carriers, disintegrants, glidants, lubricants, coatings, binders, humectants and stabilizing agents.

3. Pharmaceutical composition, according to claim 1, characterized in that the first phase comprising rosuvastatin further comprises: at least one of a diluent selected from the group consisting of lactose monohydrate, microcrystalline cellulose, anhydrous calcium phosphate and corn starch; a stabilizing agent selected from the group consisting of phosphate derivatives, including anhydrous dibasic calcium phosphate and aluminum and magnesium silicate; a disintegrant selected from the group consisting of croscarmellose sodium, cellulose derivatives including hydroxypropylcelluloses, carboxymethylcelluloses, microcrystalline cellulose, povidone derivatives including plasdones, starch derivatives including pregelatinized starch, sodium starch glycolate and corn starch;a selected slip agent from the group consisting of colloidal silicon dioxide, cellulose derivatives, including carboxymethylcelluloses, microcrystalline cellulose, starch derivatives, including pregelatinized starch and corn starch, silicate derivatives, including magnesium silicate, magnesium trisilicate and talc; and a selected lubricant from the group consisting of stearate derivatives, including zinc stearate, magnesium stearate, calcium stearate, stearic acid, monostearates, stearyl fumarate, sulfate derivatives, including magnesium lauryl sulfate and talc.

4. Pharmaceutical composition, according to claim 3, characterized in that the first phase, which additionally comprises rosuvastatin, comprises two lubricants.

5. Pharmaceutical composition, according to claim 3 or 4, characterized in that the first phase comprising rosuvastatin further comprises lactose monohydrate as a diluent, dibasic calcium phosphate as a stabilizing agent, croscarmellose sodium as a disintegrant, colloidal silicon dioxide as a glidant, talc as a first lubricant and zinc stearate as a second lubricant and a polyvinyl acetate coating.

6. Pharmaceutical composition, according to any one of claims 3 to 5, characterized in that the first phase comprising rosuvastatin further comprises: - rosuvastatin or a pharmaceutically acceptable salt thereof as the active ingredient in a dosage of 10 mg to 20 mg of rosuvastatin; - lactose monohydrate in an amount of 40% to 80% by weight of the tablet; - dibasic calcium phosphate as a stabilizing agent in an amount of 0.26% to 2% by weight of the tablet; - croscarmellose sodium as a disintegrant in an amount of 0.5% Petition 870260045829, dated 14 / 05 / 2026, p.13 / 20 3 / 9 at 15% by weight of the tablet; - colloidal silicon dioxide as a glidant in an amount of 0.08% to 2% by weight of the tablet; - talc as the first lubricant in an amount of 0.5% to 10% by weight of the tablet; - zinc stearate as a second lubricant in an amount of 0.5% to 10% by weight of the tablet; and - a polyvinyl acetate coating in an amount of 0.5% to 10% by weight of the tablet.

7. Pharmaceutical composition according to claim 6, characterized in that, in addition, rosuvastatin is rosuvastatin calcium.

8. Pharmaceutical composition according to claim 7, characterized in that the tablet additionally comprises 10.40 mg to 20.80 mg of rosuvastatin calcium.

9. Pharmaceutical composition, according to any one of claims 4 to 8, characterized in that it further comprises the rosuvastatin tablet coating, which is present in an amount of 0.5% to 6% by weight of the tablet.

10. Pharmaceutical composition, according to claim 1, characterized in that the second phase comprising acetylsalicylic acid further comprises: at least one of a diluent selected from the group consisting of starch derivatives, including pregelatinized starch and corn starch; cellulose derivatives, including microcrystalline cellulose, carbomers, hydroxypropylcellulose and carboxymethylcellulose; polyethylene glycol in its different grades; and poloxamer; Petition 870260045829, dated 05 / 14 / 2026, page 14 / 20 4 / 9 a binder selected from the group consisting of glyceryl dibehenate; povidone and its derivatives; cellulose derivatives, including carbomers, hydroxypropylcellulose, carboxymethylcellulose; starch derivatives, including pregelatinized starch and corn starch; polyethylene glycol in its different grades; and poloxamer; a humectant selected from the group consisting of sodium lauryl sulfate; poloxamers;Polyoxyethylene castor oil derivative; benzalkonium chloride; benzethonium chloride; polyoxyethylene alkyl ethers; and polyoxyethylene sorbitan fatty acid esters; a slipper selected from the group consisting of colloidal silicon dioxide; cellulose derivatives, including carboxymethylcelluloses and microcrystalline cellulose, starch derivatives, including pregelatinized starch and corn starch, silicate derivatives, including magnesium silicate and magnesium trisilicate; and talc; and a lubricant selected from the group consisting of stearate derivatives, including magnesium stearate, zinc stearate, calcium stearate, stearic acid, monostearanes and stearyl fumarate, sulfate derivatives, including magnesium lauryl sulfate and sodium lauryl sulfate; and talc.

11. Pharmaceutical composition, according to claim 10, characterized in that the binder is additionally glyceryl dibehenate, the humectant is lauryl sulfate, the glide is colloidal silicon dioxide, the lubricant is zinc stearate, and the diluent is selected from the group consisting of pregelatinized starch and microcrystalline cellulose.

12. Pharmaceutical composition, according to claim 10 or 11, characterized in that the acetylsalicylic acid granules additionally comprise two diluents.

13. Pharmaceutical composition, according to any of claims 10 to 12, characterized in that the acetylsalicylic acid granules further comprise: - acetylsalicylic acid as the active ingredient in a dosage of 100 mg; - pregelatinized starch as the first diluent in an amount of 5% to 75% by weight of the granules; - glyceryl dibehenate as a binder in an amount of 0.4% to 4% by weight of the granules; - microcrystalline cellulose as a second diluent in an amount of 5% to 90% by weight of the granules; - sodium lauryl sulfate as a humectant in an amount of 0.02% to 4% by weight of the granules; - Colloidal silicon dioxide as a slip agent in an amount of 0.08% to 2% by weight of the granules; and - Zinc stearate as a lubricant in an amount of 0.1% to 1%.

14. Pharmaceutical composition, according to any one of claims 1 to 13, characterized in that it is additionally in solid form.

15. Pharmaceutical composition, according to any one of claims 1 to 14, characterized in that it is additionally a capsule.

16. Pharmaceutical composition, according to any one of claims 1 to 15, characterized in that it further comprises: (a) a first phase comprising: - 10.4 mg of rosuvastatin calcium; Petition 870260045829, dated 05 / 14 / 2026, p.16 / 20 6 / 9 - 50.20 mg of lactose monohydrate; - 1.20 mg of dibasic calcium phosphate; - 3.5 mg of croscarmellose sodium; - 0.40 mg of colloidal silicon dioxide; - 3.6 mg of talc; - 0.70 mg of zinc stearate; and - 3 mg of a polyvinyl acetate coating; wherein the first phase of rosuvastatin is a coated tablet; (b) a second phase comprising: - 100 mg of acetylsalicylic acid; - 129.10 mg of pregelatinized starch; - 10 mg of glyceryl dibehenate; - 50 mg of microcrystalline cellulose; - 9.4 mg of sodium lauryl sulfate; - 0.75 mg of colloidal silicon dioxide; and - 0.75 mg of zinc stearate; wherein the second phase of acetylsalicylic acid is a granule; and the pharmaceutical form containing the first phase of rosuvastatin and the second phase of acetylsalicylic acid is a capsule.

17. Pharmaceutical composition, according to any one of claims 1 to 15, characterized in that it further comprises: (a) a first phase comprising: - 20.8 mg of rosuvastatin calcium; - 39.80 mg of lactose monohydrate; - 1.20 mg of dibasic calcium phosphate; - 3.5 mg of croscarmellose sodium; Petition 870260045829, dated 05 / 14 / 2026, p.17 / 20 7 / 9 - 0.40 mg of colloidal silicon dioxide; - 3.6 mg of talc; - 0.70 mg of zinc stearate; and - 3 mg of a polyvinyl acetate coating; wherein the first phase of rosuvastatin is a coated tablet; (b) a second phase comprising: - 100 mg of acetylsalicylic acid; - 129.10 mg of pregelatinized starch; - 10 mg of glyceryl dibehenate; - 50 mg of microcrystalline cellulose; - 9.4 mg of sodium lauryl sulfate; - 0.75 mg of colloidal silicon dioxide; and - 0.75 mg of zinc stearate; wherein the second phase of acetylsalicylic acid is a granule; and the pharmaceutical form containing the first phase of rosuvastatin and the second phase of acetylsalicylic acid is a capsule.

18. A manufacturing process for a pharmaceutical composition defined in any one of claims 1 to 17, characterized in that it comprises the following steps: a) providing a first phase comprising rosuvastatin, wherein the first phase comprising rosuvastatin is a coated tablet; b) providing a second phase comprising acetylsalicylic acid, wherein the second phase comprising acetylsalicylic acid is a granule; and c) encapsulating the first phase comprising rosuvastatin and the second phase comprising acetylsalicylic acid.

19. Process, according to claim 18, characterized in that the first phase, which additionally comprises coated rosuvastatin, is carried out with the following steps: - mixing the rosuvastatin with a glidant, a disintegrant, a stabilizing agent, a diluent and a first lubricant; - lubricating the previous mixture with at least one lubricant; - compressing the lubricated mixture to obtain a rosuvastatin tablet; - coating the tablet.

20. Process according to claim 19, characterized in that the diluent is additionally lactose monohydrate, the stabilizing agent is dibasic calcium phosphate, the disintegrant is croscarmellose sodium, the glidant is colloidal silicon dioxide, the solvent is purified water, the first lubricant is talc, the second lubricant is zinc stearate, and the coating is polyvinyl acetate.

21. Process according to claim 18, characterized in that the second phase, which additionally comprises acetylsalicylic acid, is prepared with the following steps: - mixing the acetylsalicylic acid with a humectant, a first diluent and a binder; - granulating and heating the previous mixture; - cooling the mixture and adding a glide and a second diluent; - lubricating the mixture with a lubricant.

22. Process according to claim 19, characterized in that the binder is additionally glyceryl dibehenate, the humectant is lauryl sulfate, the glide is colloidal silicon dioxide, the lubricant is zinc stearate, the first diluent is pregelatinized starch and the second diluent is microcrystalline cellulose.

23. Process, according to claim 18, characterized by the fact that step c) of encapsulation further comprises introducing the first phase comprising rosuvastatin and the second phase comprising acetylsalicylic acid into a gelatin capsule.

24. Use of a pharmaceutical composition defined in any one of claims 1 to 17, characterized in that it is for the manufacture of a medicament useful in the treatment of hyperlipidemia and the prevention of at least one cardiovascular disease.

25. Use according to claim 24, characterized in that hyperlipidemia and cardiovascular disease are selected from the group consisting of hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia, hypertension, angina, infarctions and aneurysms.

26. Use, according to claim 25, characterized in that the pharmaceutical composition regulates the blood concentration of low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides, and cholesterol. Petition 870260045829, dated 05 / 14 / 2026, page 20 / 20

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