SOLID ORAL COMPOSITION AND PROCESS FOR PREPARING A SOLID ORAL COMPOSITION OF OLAPARIB

Abstract

The present invention discloses a novel solid oral pharmaceutical composition of olaparib or pharmaceutically acceptable salts thereof in the solid oral dosage form preferably in the form of a tablet and its process for preparations thereof. The present invention further discloses a solid oral pharmaceutical composition of olaparib or its pharmaceutically acceptable salts thereof along with a hydrophilic matrix polymer.

Description

1 / 26 “SOLID ORAL COMPOSITION AND PROCESS FOR PREPARING A SOLID ORAL COMPOSITION OF OLAPARIB” Field of the invention

[001] The present invention relates to a novel solid pharmaceutical composition of Olaparib or its salt that is pharmaceutically acceptable for oral dosing and to the process for its preparation. The Olaparib composition containing one or more matrix polymers provided by the present invention exhibits an excellent in vitro dissolution profile, and is safe and stable. Background of the invention

[002] Olaparib is a poly(ADP-ribose) polymerase (PARP) inhibitor used to treat ovarian cancer, breast cancer, pancreatic cancer, and prostate cancer. Olaparib is chemically known as 4-(3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazine-1-one and structurally is represented as follows: OLAPARIB

[003] Olaparib is disclosed in U.S. Patent No. 8,475,842 and is marketed under the brand name Lynparza®, which is a film-coated tablet. The patent describes an immediate-release pharmaceutical composition. Petition 870250080814, dated 09 / 09 / 2025, page 14 / 44 2 / 26 of Olaparib in the form of a solid dispersion, prepared by solvent evaporation (spray drying method) or hot melt extrusion, in which the composition contains Olaparib in amorphous form, together with a matrix polymer, such as a copovidone polymer, wherein the weight ratio of Olaparib to polymer is in the range of 1:2 to 1:4. US document 8475842 states that povidone unexpectedly failed to provide a stable solid dispersion formulation for Olaparib and that 2. Solid dispersions produced with the relatively hygroscopic polymer povidone tended to crystallize when stored at 40 °C / 75% relative humidity, leading to a reduction in the dissolution rate.

[004] Document US20200108008 describes a sustained-release, controlled-release oral pharmaceutical composition of Olaparib containing a rate-adjusting matrix polymer, such as povidone, for an enhanced dissolution form, wherein the composition is in the form of a solid dispersion containing Olaparib, a matrix polymer, such as povidone, and other additives, such as surfactants, a lubricant, a colloidal silica, a plasticizer, and the like.

[005] Document US10662178 describes a pharmaceutical composition comprising a crystalline form of Olaparib together with benzyl alcohol and one or more pharmaceutically acceptable excipients, wherein the composition is in the form of a tablet or capsule.

[006] Document EP4079295 describes an amorphous oral solid dispersion composition of Olaparib in which the composition contains a polymethacrylate copolymer in which the Petition 870250080814, dated 09 / 09 / 2025, page 15 / 44 3 / 26 polymethacrylate copolymer is poly(butyl methacrylate-co(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate).

[007] Document CN104434809 describes solid dispersion particles of Olaparib, comprising compositions of Olaparib, povidone and lubricant.

[008] The technical data described above describe the preparation of a solid dispersion of Olaparib using a large amount of polymers as adjuvants to improve the bioavailability of the drug, and the patient faces the problem of the convenience of administration during administration. Thus, there remains a need for a solid dispersion formulation of Olaparib in which the amount of adjuvants used in the formulation can be reduced and the formulation remains stable with improved dissolution, which increases the convenience of medication for patients. The inventors of the present invention have solved the problem by synergistically using a mixture or blend of polymers in the present invention, which significantly improves the dissolution behavior of the active ingredient, i.e., Olaparib, and thus reduces the amount of excipients used and improves the bioavailability of active ingredients and are easy to industrialize.

[009] The prior art references above describe different compositions comprising Olaparib. However, there is a need for the development of alternative formulations comprising Olaparib. The inventors of the present invention have surprisingly discovered that a tablet composition comprising Olaparib containing one or more matrix polymers is possible. The present invention presents Petition 870250080814, dated 09 / 09 / 2025, page 16 / 44 4 / 26 an excellent in vitro dissolution profile, being safe and stable.

[010] There is a need to provide oral solid dispersion compositions of Olaparib that contain a matrix polymer with improved bioavailability, stability and drug loading when compared to other Olaparib tablet compositions. The present invention also relates to a process for preparing these new pharmaceutical compositions. Summary of the invention

[011] The present invention involves a solid dispersion composition of Olaparib in tablet form, wherein the composition contains Olaparib, one or more matrix polymers and one or more pharmaceutically acceptable excipients.

[012] In one embodiment, the present invention involves a solid dispersion composition of Olaparib together with a matrix polymer, povidone, including, among others, Povidone K12, Povidone K90, Povidone K25, Povidone K30, povidone 12PF, povidone 17PF or povidone K25, and in another embodiment, the weight ratio of Olaparib to polymer is in the range of 1: > 4.

[013] In another embodiment, the present invention involves a solid dispersion composition of Olaparib along a matrix polymer, wherein the matrix polymer is a hydrophilic polymer with a glass transition temperature in the range of 40°C to 100°C, including, among others, a polyvinyl caprolactam / polyvinyl acetate / polyethylene glycol copolymer (soluplus) and / or copolymers based on dimethyl aminoethyl methacrylate, butyl methacrylate and methyl Petition 870250080814, dated 09 / 09 / 2025, page 17 / 44 5 / 26 methacrylate, and wherein the weight ratio of Olaparib to the polymer is in any range. In another embodiment, the present invention involves a solid dispersion composition of Olaparib throughout a polymer matrix that includes, among others, copovidone, hypromellose phthalate (hydroxypropylmethylcellulose phthalate, HPMCP), HPMC HP-50 phthalate, HPMC E6, hypromellose acetate succinate (hydroxypropylmethylcellulose acetate succinate, HPMCAS), 2-hydroxypropyl-β-cyclodextrin (HPBCD), hypromellose (hydroxypropylmethylcellulose, HPMC), polymethacrylates (poly(methacrylic acid, methyl methacrylate 1:1; poly(methacrylic acid, ethyl acrylate) 1:1), hydroxypropylcellulose (HPC) and cellulose acetate phthalate (CAP), wherein the weight ratio of Olaparib to polymer is in any range.

[014] In another embodiment, the solid dispersion composition of Olaparib or its pharmaceutically acceptable salts, together with one or more. Excipients include, among others, fillers, binders, disintegrants, lubricants, preservatives, stabilizers, antioxidants, silica flow conditioners, anti-adherents, glidants, solubility enhancers and / or coating agents and / or colorants.

[015] In another embodiment, the methods for preparing the solid dispersion composition of Olaparib or its pharmaceutically acceptable salts include, among others, aqueous granulation, kneading method, solvent evaporation, spray drying process, lyophilization, supercritical fluid, coprecipitation and Petition 870250080814, dated 09 / 09 / 2025, page 18 / 44 6 / 26 electrospinning. Brief description of the drawings

[016] Figure 1: illustrates the in vitro dissolution profile of the product of the present invention with a reference product (Lynparza® 150 mg tablet) at 100 RPM in 900 mL of phosphate buffer pH 6.8, basket (Basket) at (37 ± 0.5)°C. Detailed description of the invention

[017] The nature of the invention is clearly described in the descriptive report. The invention has several components, which are clearly described in the descriptive report. The present invention will now be disclosed by describing certain preferred and optional embodiments, to facilitate various aspects thereof.

[018] The present invention describes a method for preparing a solid dispersion, comprising the steps of dissolving the drug and the polymer in a common solvent and evaporating the solvent. The solvent is carefully selected according to the polymer used. Examples of solvents are: acetone, acetone / dichloromethane, methanol / dichloromethane, acetone / water, acetone / methanol, acetone / ethanol, dichloromethane / ethanol or ethanol / water. Methods for solvent evaporation include vacuum drying, spray drying, tray drying, freeze-drying or other drying techniques, rotary evaporation, freeze-drying and thin-film evaporation. Alternatively, solvent removal can be carried out by cryogenic freezing followed by freeze-drying.

[019] In one aspect of the present invention, one or more filling agents include, among others, lactose, sugar, starches, modified starches, mannitol, sorbitol, salts Petition 870250080814, dated 09 / 09 / 2025, page 19 / 44 7 / 26 Inorganic, cellulose derivatives (e.g., microcrystalline cellulose, cellulose), calcium sulfate, xylitol, and lactitol.

[020] In another aspect of the present invention, one or more channeling agents include, among others, mannitol, sodium chloride, sugars, polyol and EMDEX® (glucose monohydrate and different starch-derived polysaccharides).

[021] In another aspect of the present invention, one or more binders include, among others, lactose, starches, modified starches, sugars, acacia gum, tragacanth gum, guar gum, pectin, wax binders, microcrystalline cellulose, methylcellulose, carboxymethylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, copovidone, gelatin, polyvinylpyrrolidone (PVP) and sodium alginate.

[022] In another aspect of the present invention, one or more disintegrants include, among others, crosslinked polymers, including crosslinked polyvinylpyrrolidone (crospovidone), crosslinked sodium carboxymethylcellulose (croscarmellose sodium) and modified starch, sodium starch glycolate.

[023] In another aspect of the present invention, one or more lubricants include, among others, magnesium stearate, magnesium lauryl stearate, sodium stearyl fumarate, stearic acid, calcium stearate, zinc stearate, potassium benzoate, sodium benzoate, myristic acid, palmitic acid, mineral oil, hydrogenated castor oil, medium-chain triglycerides, poloxamer, polyethylene glycol and talc. Petition 870250080814, dated 09 / 09 / 2025, p. 20 / 44 8 / 26

[024] In another aspect of the present invention, one or more preservatives include, among others, sodium benzoate, EDTA, sorbic acid and parabens.

[025] In another aspect of the present invention, one or more stabilizers include, among others, PVP (Povidone), PVA (Polyvinyl Alcohol), PEG (Polyethylene Glycol), HPMC (Hypromellose), HPC (Hydroxypropylcellulose) and HEC (Hydroxyethylcellulose).

[026] In another aspect of the present invention, one or more antioxidants include, among others, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium metabisulfite (SMB), propyl gallate (PG) and cysteine ​​(CYS).

[027] In another aspect of the present invention, one or more non-stick agents include, among others, Tween®-80 (Polysorbate-80), sodium lauryl sulfate (sodium dodecyl sulfate), Labrafil® (PEGylated oils) and Labrasol® (PEGylated caprylic / capric glycerides).

[028] In one aspect of the present invention, one or more slip agents include, among others, talc, colloidal silicon dioxide, magnesium stearate and silica.

[029] In another aspect of the present invention, one or more solubility enhancers include, among others, magnesium aluminometasilicate, Sepitrap 80 or any combination thereof.

[030] In another aspect of the present invention, one or more coating agents include, among others, Opadry, polyvinyl alcohol (PVA), Eudragit® EPO, hydroxypropyl methylcellulose (HPMC), hydroxyethylcellulose (HEC) and polyvinyl alcohol-polyethylene glycol copolymer ( Petition 870250080814, dated 09 / 09 / 2025, page 21 / 44 9 / 26 PVA-PEG).

[031] In another aspect of the present invention, one or more coloring agents include, among others, red ferric oxide, titanium oxide, lead oxide, copper sulfate and carbon black.

[032] In another aspect of the present invention, Olaparib or its pharmaceutically acceptable salts are present in an amount of 10 to 50%, more preferably 15 to 45% by weight of the total weight of the pharmaceutical composition.

[033] In another aspect of the present invention, the polymer in the composition is present in an amount of 1 to 95%, more preferably 2% to 85% by weight of the total weight of the pharmaceutical composition.

[034] In another aspect of the present invention, one or more fillers in the composition are present in an amount of 1 to 70%, more preferably 3 to 7% by weight of the total weight of the pharmaceutical composition.

[035] In another aspect of the present invention, one or more fillers in the composition are present in an amount of 2 to 40% by weight of the total weight of the pharmaceutical composition.

[036] In another aspect of the present invention, one or more disintegrants in the composition are present in an amount of 1 to 20% by weight of the total weight of the pharmaceutical composition.

[037] In another aspect of the present invention, one or more lubricants in the composition are present in an amount of 0.5 to 3%, more preferably 0.5 to 3% by weight of the total weight of the pharmaceutical composition.

[038] In another aspect of the present invention, one or more Petition 870250080814, dated 09 / 09 / 2025, page 22 / 44 10 / 26 preservatives in the composition are present in an amount of 0.02 to 0.5% by weight of the total weight of the pharmaceutical composition.

[039] In another aspect of the present invention, one or more stabilizers in the composition are present in an amount of 0.5 to 10% by weight of the total weight of the pharmaceutical composition.

[040] In another aspect of the present invention, one or more antioxidants in the composition are present in an amount of 0.05 to 0.9% by weight of the total weight of the pharmaceutical composition.

[041] In another aspect of the present invention, one or more anti-adherents in the composition are present in an amount of 5 to 20% by weight of the total weight of the pharmaceutical composition.

[042] In another aspect of the present invention, one or more glide agents in the composition are present in an amount of 0.5 to 3.0%, more preferably 0.5 to 1.5% by weight of the total weight of the pharmaceutical composition.

[043] In another aspect of the present invention, one or more film coating agents in the composition are present in an amount of 1 to 3% by weight of the total weight of the pharmaceutical composition.

[044] In another aspect, the present invention relates to a process for preparing a solid oral composition of Olaparib by the spray-drying technique: a) Prepare a solid dispersion of Olaparib with one or more matrix polymers using solvent, b) Spray drying of the Olaparib solid dispersion to remove solvents using equipment for Petition 870250080814, dated 09 / 09 / 2025, page 23 / 44 11 / 26 spray drying, c) sieve the solid dispersion of Olaparib by means of co-sieving with fillers and a slip agent, d) sieve the lubricant, e) pre-mixing the sieved material from step (c) in the mixer and lubricating the mixture with the lubricant from step (d), f) mixing and demixing, g) mix and lubricate with lubricant, h) compress into a tablet, i) Coat with a coating agent in purified water to form a film-coated tablet.

[045] The inventors of the present invention surprisingly obtained better intact properties of the composition and improved release profile when the mixture of one or more polymers is in the ratio of 1: > 4. The addition of one or more polymers, preferably in the ratio of 1:>4, to the preparation of the composition improves the release profile and solubility, and the dissolution profile was similar to that of the reference product (Lynparza® 150 mg tablet).

[046] The term oral administration means that the active agent is in a formulation designed to be ingested, that is, designed to be delivered to the gastrointestinal system for absorption.

[047] The term solid oral composition includes capsule, tablet (film-coated tablet, controlled-release tablet, modified-release tablet, extended-release tablet, delayed-release tablet, immediate-release tablet, etc.), microtablet, powder, granules and Petition 870250080814, dated 09 / 09 / 2025, p. 24 / 44 12 / 26 pellets. The capsules used as an oral dosage form may be soft or hard capsules, although the oral dosage form of the present invention is the tablet.

[048] The term % w / w refers to the value relative to the total weight of the granules or the total weight of the pharmaceutical composition, and % v / v refers to the percentage of volume per total volume.

[049] The pharmaceutical composition described herein is stable throughout its shelf life when subjected to accelerated and long-term stability studies.

[050] The present invention has been described only as an example. It should be recognized that modifications that fall within the scope and spirit of the claims, which would be obvious to a person skilled in the art based on the description given herein, are also considered to be included within the scope of this invention. The scope of the invention is in no way limited by the example described. Petition 870250080814, dated 09 / 09 / 2025, page 25 / 44 13 / 26 EXAMPLE 1: Table 1: Preparation of a tablet containing Olaparib and Povidone K12 PF (API / Polymer ratio - 1:4.5) Mr. No. Ingredients Mg / Tablet %s / s 150 mg Binder solution 1 Olaparib 150.00 18.18 2 Povidone K12 PF 675.00 81.82 3 Methanol q.s. 4 Dichloromethane q.s. Total weight of dispersion 825.00 100.00 Intragranular materials 5 Spray-dried Olaparib material 825.00 91.67 6 Mannitol (200 DP) 52.50 5.83 7 Colloidal silicon dioxide 9.00 1.00 Lubrication (Pre-emollient) (pre-slugging) 8 Sodium stearyl fumarate 4.50 0.50 Lubrication 9 Sodium stearyl fumarate 9.00 1.00 Total weight of coated tablet 900.00 100.00 Petition 870250080814, dated 09 / 09 / 2025, page 26 / 44 14 / 26 EXAMPLE 2: Table 2: Preparation of a tablet containing Olaparib and Povidone K30 (API / Polymer ratio - 1:4.5) Mr. No. Ingredients Mg / Tablet %s / s 150 mg Binder solution 1 Olaparib 150.00 18.18 2 Povidone K30 675.00 81.82 3 Methanol q.s. 4 Dichloromethane q.s. Total weight of dispersion 825.00 100.00 Intragranular materials 5 Spray-dried Olaparib material 825.00 91.67 6 Mannitol (200 DP) 52.50 5.83 7 Colloidal silicon dioxide 9.00 1.00 Lubrication (Pre-emollient) 8 Sodium stearyl fumarate 4.50 0.50 Lubrication 9 Sodium stearyl fumarate 9.00 1.00 Total weight of coated tablet 900.00 100.00 Petition 870250080814, dated 09 / 09 / 2025, page 27 / 44 15 / 26 EXAMPLE 3: Table 3: Preparation of a tablet containing Olaparib and Povidone K30 with Povidone K90 (API / Polymer ratio - 1:4.5) Mr. No. Ingredients Mg / Tablet %s / s 150 mg Binder solution 1 Olaparib 150.00 18.18 2 Povidone K30 658.12 79.77 3 Povidone K90 16.88 2.05 4 Methanol q.s. 5 Dichloromethane q.s. Total weight of dispersion 825.00 100.00 Intragranular materials 6 Spray-dried Olaparib material 825.00 91.67 7 Mannitol (200 DP) 52.50 5.83 8 Colloidal silicon dioxide 9.00 1.00 Lubrication (Pre-emollient) 9 Sodium stearyl fumarate 4.50 0.50 Lubrication 10 Sodium stearyl fumarate 9.00 1.00 Total weight of coated tablet 900.00 100.00 Petition 870250080814, dated 09 / 09 / 2025, page 28 / 44 16 / 26 EXAMPLE 4: Table 4: Preparation of a tablet containing Olaparib and Povidone K30 with Povidone K90 (API / Polymer ratio - 1:4.5) Mr. No. Ingredients Mg / Tablet %s / s 150 mg Binder solution 1 Olaparib 150.00 18.18 2 Povidone K30 641.25 77.73 3 Povidone K90 33.75 4.09 4 Methanol q.s. 5 Dichloromethane q.s. Total weight of dispersion 825.00 100.00 Intragranular materials 6 Spray-dried Olaparib material 825.00 91.67 7 Mannitol (200 DP) 52.50 5.83 8 Colloidal silicon dioxide 9.00 1.00 Lubrication (Pre-emollient) 9 Sodium stearyl fumarate 4.50 0.50 Lubrication 10 Sodium stearyl fumarate 9.00 1.00 Total weight of coated tablet 900.00 100.00 Petition 870250080814, dated 09 / 09 / 2025, page 29 / 44 17 / 26 EXAMPLE 5: Table 5: Preparation of a tablet containing Olaparib and Povidone K30 with Povidone K90 (API / Polymer ratio - 1:4.5) Mr. No. Ingredients Mg / Tablet %s / s 150 mg Binder solution 1 Olaparib 150.00 18.18 2 Povidone K30 641.25 77.73 3 Povidone K90 33.75 4.09 4 Methanol q.s. 5 Dichloromethane q.s. Total weight of dispersion 825.00 100.00 Intragranular materials 6 Spray-dried Olaparib material 825.00 91.67 7 Mannitol (200 DP) 52.50 5.83 8 Colloidal silicon dioxide 9.00 1.00 Lubrication (Pre-emollient) 9 Sodium stearyl fumarate 4.50 0.50 Lubrication 10 Sodium stearyl fumarate 9.00 1.00 Total weight of coated tablet 900.00 100.00 Petition 870250080814, dated 09 / 09 / 2025, page 30 / 44 18 / 26 EXAMPLE 6: Table 6: Preparation of a tablet containing Olaparib and Povidone K30 with Povidone K90 (API / Polymer ratio - 1:4.0) Mr. No. Ingredients Mg / Tablet %s / s 150 mg Binder solution 1 Olaparib 150.00 20.00 2 Povidone K30 570.00 76.00 3 Povidone K90 30.00 4.00 4 Methanol q.s. 5 Dichloromethane q.s. Total weight of dispersion 750.00 100.00 Intragranular materials 6 Spray-dried Olaparib material 825.00 91.67 7 Mannitol (200 DP) 52.50 5.83 8 Colloidal silicon dioxide 9.00 1.00 Lubrication (Pre-emollient) 9 Sodium stearyl fumarate 4.50 0.50 Lubrication 10 Sodium stearyl fumarate 9.00 1.00 Total weight of coated tablet 900.00 100.00 Petition 870250080814, dated 09 / 09 / 2025, page 31 / 44 19 / 26 EXAMPLE 7: Table 7: Preparation of a tablet containing Olaparib and Povidone K30 with Povidone K90 (API / Polymer ratio - 1:3.0) Mr. No. Ingredients Mg / Tablet %s / s 150 mg Binder solution 1 Olaparib 150.00 25.00 2 Povidone K30 427.00 71.25 3 Povidone K90 22.50 3.75 4 Methanol q.s. 5 Dichloromethane q.s. Total weight of dispersion 825.00 100.00 Intragranular materials 6 Spray-dried Olaparib material 825.00 91.67 7 Mannitol (200 DP) 52.50 5.83 8 Colloidal silicon dioxide 9.00 1.00 Lubrication (Pre-emollient) 9 Sodium stearyl fumarate 4.50 0.50 Lubrication 10 Sodium stearyl fumarate 9.00 1.00 Total weight of coated tablet 900.00 100.00 Petition 870250080814, dated 09 / 09 / 2025, pages 32 / 44 20 / 26 EXAMPLE 8: Table 8: Preparation of a tablet containing Olaparib and Povidone K30 with Povidone K90 (API / Polymer ratio - 1:4.0) Mr. No. Ingredients Mg / Tablet Mg / Tablet %s / s 100 mg 150 mg Binder solution 1 Olaparib 100.00 150.00 20.00 2 Povidone K30 380.00 570.00 76.00 3 Povidone K90 20.00 30.00 4.00 4 Methanol q.s. q.s. 5 Dichloromethane q.s. q.s. Total weight of dispersion 500.00 750.00 100.00 Intragranular materials 6 Spray-dried Olaparib material 500.00 750.00 92.59 7 Mannitol (200 DP) 25.00 37.50 4.63 8 Colloidal silicon dioxide 6.00 9.00 1.11 Lubrication (Pre-emollient) 9 Sodium stearyl fumarate 3.00 4.50 0.56 Lubrication 10 Sodium stearyl fumarate 6.00 9.00 1.11 Total weight of lubricated mixture 540.00 810.00 100.00 Coating film 11 Opadry AMB II 88ZA540003 Pink 12.15 18, 23 12 Purified water q.s. q.s. Total weight of coated tablets 552.15 828.23 DISSOLUTION STUDY

[051] Dissolution rate is a critical property that is a prerequisite for the final pharmaceutical form. The comparative dissolution profile of Petition 870250080814, dated 09 / 09 / 2025, pages 33 / 44 21 / 26 The product of the present invention was compared with a reference product. It was found that the dissolution of the present invention in relation to the reference product was comparable. Complete release and therefore increased solubility was achieved.

[052] The dissolution study of the pharmaceutical dosage of the present invention was performed by HPLC. The dissolution method employed in the present invention is the USP I apparatus with a sinker at 100 RPM in 900 mL of phosphate buffer pH 6.8, basket at (37 ± 0.5)°C. Samples were collected at 10, 15, 30, 45, 60, and 90 minutes. The sample was filtered through a 0.45 μm syringe filter, transferred to HPLC vials, and analyzed by HPLC. Tablet 9 presents comparative dissolution data of the Olaparib tablet from the reference product in relation to the product of the present invention. Table 9: Comparative study of tablet dissolution. Olaparib of the present invention with the reference product. Reference Product Test Lynparza (Olaparib) 150 mg Example 6 and 8 API: Povidone K30 / K90 — (1:4.0) Example 4 API: Povidone K30 / K90 — (1:4.5) Time (min) % Drug Release % Drug Release % Drug Release 10 14.40 14.90 18.00 15 25.02 26.90 30.00 30 53.86 56.90 59.20 45 76.66 76.50 78.60 60 90.72 86.40 89.60 90 94.73 91.14 95.20 Recording 93. 99 90.76 95.00 F2 78.36 70.41 Similarity factor: The F2 value between 50 and 100 Petition 870250080814, dated 09 / 09 / 2025, pages 34 / 44 22 / 26 establishes the similarity of the two dissolution profiles. The physical parameters of the tablets were considered satisfactory. Slow and uniform erosion was observed for up to 35 minutes. STABILITY STUDY

[053] The inventors of the present invention have surprisingly found that the Olaparib tablets of the present invention underwent rapid and complete dissolution initially compared to the reference product. The Olaparib tablets of the present invention underwent rapid and complete dissolution even after 6 months, when tested using the USP Apparatus (I), compared to the innovator's reference product. An increase in solubility and dissolution rates leads to a consistent and uniform improvement in drug bioavailability.

[054] The composition according to the present invention was subjected to stability studies under stability analysis conditions of 40°C ± 2°C and relative humidity of 75% ± 5%. The Olaparib tablets of the present invention are adequately stable according to the general stability requirements under these conditions. In addition, the Olaparib tablets of the present invention are also stable under accelerated stability conditions.

[055] The present invention is stable in storage for extended periods. The composition is stable and the stability study of the coated tablets with Povidone K30 and Povidone K90 (ratio 1:4.0) is presented in Table 10. Petition 870250080814, dated 09 / 09 / 2025, pp. 35 / 44 23 / 26 Table 10: Stability study of the Olaparib tablet of the present invention Initial Stability Station 1 month 3 month 6 month Initial Condition 40°C / 75%RH 40°C / 75%RH 40°C / 75%RH Test (%) 99.05 103.9 95.47 NA Impurity 1 0.071 0.00 0.00 0.00 Impurity 2 ND 0.00 0.07 0.06 Impurity 3 ND 0.00 0.00 0.01 Maximum Unknown Single Impurity 0.03 0.04 0.04 0.04 Total (NMT 2.0%) 0.16 0.17 0.25 0.26 Dissolution pH 6.8, 900 ml, Basket, 100 RPM USP-I 92,40 90, 80 90, 34 93, 22 *ND = Not detected

[056] As indicated in the table above, the result of the stability study proves that the Olaparib composition, according to the present invention, exhibits excellent storage stability.

[057] The inventors of the present invention carried out disintegration and dissolution studies with other polymers using the spray drying technique, which were unsatisfactory. A satisfactory dissolution profile and an increase in solubility were not achieved, as illustrated below. Petition 870250080814, dated 09 / 09 / 2025, pages 36 / 44 24 / 26 Table 11: Olaparib and Soluplus (API / Polymer ratio 1:2.57) Test Results Assay 100.04% Dissolution (Olaparib Soft Gelatin Capsule Medium) Phosphate buffer pH 6.8, Basket, 100 RPM, 900 mL Time (min) % Drug Release 30 5.68 60 10.89 Recording 19.63 Table 12: Olaparib and Soluplus with Polysorbate 80 (ratio API / Polymer - 1:1.5) Test Results Assay NA Dissolution (Olaparib Soft Gelatin Capsule Medium) Phosphate buffer pH 6.8, Basket, 100 RPM, 900 mL Time (min) % Drug Release 30 21.73 60 37.77 Recording 73.44 Table 13: Olaparib and Soluplus with Polysorbate 80 (ratio API / Polymer - 1:2.25) Test Results Assay 95.45 Dissolution (Olaparib Soft Gelatin Capsule Medium) Phosphate buffer pH 6.8, Basket, 100 RPM, 900 mL Time (min) % Drug Release 30 30, 92 60 43, 49 Recording 55, 59 Petition 870250080814, dated 09 / 09 / 2025, pages 37 / 44 25 / 26 Table 14: Olaparib and HPMC Phthalate HP-50 with Polysorbate (API / Polymer ratio - 1:1.5) Test Results Assay 86.01 Dissolution (Olaparib Soft Gelatin Capsule Medium) Phosphate buffer pH 6.8, Basket, 100 RPM, 900 mL Time (min) % Drug Release 10 41.27 15 45.32 30 54.54 45 57.70 60 59.17 Recording NA Table 15: Olaparib and HPMC with Polysorbate 80 (ratio API / Polymer - 1:1.5) Test Results Assay NA Dissolution (Olaparib Soft Gelatin Capsule Medium) Phosphate buffer pH 6.8, Basket, 100 RPM, 900 mL Time (min) % Drug Release 10 33, 60 15 45, 41 30 68, 23 45 77, 70 60 81, 62 NA Recording Table 16: Olaparib and HPMC (API / Polymer ratio - 1:1.5) Test Results Assay NA Dissolution (Olaparib Soft Gelatin Capsule Medium) Phosphate buffer pH 6.8, Basket, 100 RPM, 900 mL Time (min) % Drug Release 10 17.97 15 24.83 30 42.80 45 58.11 60 70.86 NA Recording

[058] The invention described herein comprises several objects, Petition 870250080814, dated 09 / 09 / 2025, pages 38 / 44 26 / 26 as mentioned above, and its description in relation to the characteristics, compositions and process adopted. Although these aspects are emphasized in the invention, any variations of the invention described above should not be considered as a deviation from the spirit and scope of the invention, as described.

[059] The examples mentioned above are provided for illustrative purposes only and are in no way limiting to the present invention. Petition 870250080814, dated 09 / 09 / 2025, pages 39 / 44

Claims

1 / 3 CLAIMS 1. Solid oral composition, characterized by comprising Olaparib and a hydrophilic matrix polymer in a ratio of 1:

4.

2. Solid oral composition, according to claim 1, characterized in that it comprises: a) 10 to 50% w / w of solid dispersion of Olaparib, b) 1 to 95% w / w of matrix polymer or a mixture thereof, c) 0.5 to 3% w / w of lubricant or a mixture thereof, d) 0.5 to 3% w / w of glide agent, e) 1 to 10% w / w of channeling agent, f) 1 to 3% w / w of film coating agent, g) solvent or a mixture thereof and, optionally, other excipients.

3. Solid oral composition, according to claim 1, characterized in that the total amount of Olaparib in the composition is in the range of 25 mg to 250 mg.

4. Solid oral composition, according to claim 1, characterized in that the hydrophilic polymeric matrix is ​​selected from Povidone K12, Povidone K90, Povidone K25, Povidone K30, Povidone 12PF, Povidone 17PF or Povidone K25, or a mixture thereof, preferably from 2% to 85% w / w by weight of the total weight of the pharmaceutical composition.

5. Solid oral composition, according to claim 1, characterized in that the lubricant is selected from magnesium stearate, magnesium lauryl stearate, sodium stearyl fumarate, stearic acid, calcium stearate, zinc stearate, potassium benzoate, sodium benzoate and talc, or a mixture thereof, preferably from 0.5 to 3% by weight of the total weight of the pharmaceutical composition.

6. Solid oral composition, according to claim 1, characterized in that the glidant is selected from talc, colloidal silicon dioxide, magnesium stearate and silica, preferably from 0.5 to 1.5% by weight of the total weight of the pharmaceutical composition.

7. Solid oral composition, according to claim 1, characterized in that the active ingredient is selected from mannitol, sodium chloride, sugars, polyol and glucose monohydrate and polysaccharides and a mixture thereof, preferably from 1 to 6% by weight of the total weight of the pharmaceutical composition.

8. Solid oral composition, according to claim 1, characterized in that the solvent is selected from acetone, acetone and dichloromethane, methanol and dichloromethane, acetone and water, acetone and methanol, acetone and ethanol, dichloromethane and ethanol, or ethanol and water, or a mixture thereof.

9. Solid oral composition, according to claim 1, characterized in that the coating agent is present in an amount of 1 to 3% by weight of the total weight of the pharmaceutical composition.

10. Process for preparing a solid oral composition of Olaparib, characterized by comprising the spray drying technique: a) preparing a solid dispersion of Olaparib with one or more matrix polymers using solvent, b) spray drying the solid dispersion of Olaparib to remove solvents using a spray drying apparatus, c) sieving the solid dispersion of Olaparib by means of co-sieving with fillers and a slip agent, d) sieving the lubricant, e) pre-mixing the sieved material from step (c) in the mixer and lubricating the mixture with the lubricant from step (d), f) mixing and demixing, g) mixing and lubricating with lubricant, h) compressing into a tablet, i) coating with a coating agent in purified water to form a film-coated tablet. Petition 870250080814, dated 09 / 09 / 2025, pages 42 / 44

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