AZYLSARTAN-CONTAINING NANOSUSPENSION COMPOSITION

Abstract

The present invention relates to a nanosuspension composition containing i) azilsartan medoxomil and / or its pharmaceutically acceptable salts, ii) copovidone, iii) at least one surfactant, and iv) at least one pharmaceutically acceptable excipient. The said nanosuspension composition possesses desirable pharmacokinetic characteristics and stability. The invention also relates to a process for the preparation of the said nanosuspension composition and its use in the preparation of a drug useful in the treatment of hypertension.

Description

Technical Field to Which the Invention Belongs The present invention relates to i) azilsartan medoxomil and / or a pharmaceutically acceptable form of invention. i) salts, iii) at least one surfactant, and iv) at least one pharmaceutical with a nanosuspension composition containing an acceptable auxiliary substance This is relevant. The nanosuspension composition in question has a desired pharmacokinetic profile. It possesses characteristic features and stability. Furthermore, the invention, in question... a process for preparing nanosuspension composition and hypertension for use in preparing the medicine that is useful in its treatment It is related. State of the Art Azilsartan medoxomil is chemically classified as 1H-Benzimidazole-7-carboxylic acid,1- [[2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-yl]methyl]-2-ethoxy- It is known as (5-methyl-2-oxo-1,3-dioxo-4-yl)methyl ester and is described below. It has formula (I), (I). Azilsartan medoxomil is a highly selective angiotensin II type 1 receptor (AT1) agent. It is an antagonist of angiotensin II to the AT1 receptor. Its antihypertensive effects are due to its effect on the AT1 receptor of angiotensin II. They achieve this by selectively blocking the binding of angiotensin II; this results in... It reduces blood pressure by antagonizing their vasoconstrictive effects. 1 1.98 Azilsartan medoxomil has been available in Europe from Takeda Pharmaceuticals since 2011. Produced by Edarbi® in 20 mg, 40 mg and 80 mg tablets. is being marketed. Azilsartan medoxomil tablets, sold under the trade name Edarbi®, are used in adults. It is indicated for the treatment of essential hypertension. Azilsartan medoxomil is also available under the trade name Edarbyclor® in 40mg / 12.5mg and In combination with Chlorthalidone at doses of 40mg / 25mg, it was used in the United States in 2011. It has been marketed since [year]. Edarbyclor® is used in the treatment of hypertension, blood pressure To reduce the pressure: • In patients whose condition is not adequately controlled with monotherapy • Using multiple medications to achieve target blood pressure levels likely initial treatment in patients It is indicated. Edarbi® contains azilsartan medoxomil potassium salt and mannitol as active ingredients. fumaric acid, sodium hydroxide, hydroxypropylcellulose, croscarmellose sodium, It contains microcrystalline cellulose and magnesium stearate. US7157584 B2 describes azilsartan medoxomil, or its potassium salt. US7572920 B2, pharmaceutical formulations of azilsartan medoxomil and This describes the preparation process for azilsartan medoxomil. EP 2124903 B1, for azilsartan medoxomil and adjusting the pH range to 2 to 5. monosodium fumarate or a combination of fumaric acid and sodium hydroxide It describes solid formulations containing these ingredients. 2 1.98 WO2022003643 A1, Azilsartan camedoxomil and fillers, diluents, Binders, dispersants, coating agents, lubricants, surfactants, pH modifiers or pH adjusters, lubricants, carriers and polymers or One or more pharmaceutically acceptable adjuvants, such as a coating system the method of preparing a pharmaceutical composition containing the substance and pipetting It explains its use in treatment. CN111617046 A, D90 is a micronized particle with a particle size distribution smaller than 40 µm. azilsartan, dispersants, fillers, binders, stabilizers and lubricants a dispersible tablet containing pharmaceutically acceptable excipients such as It explains. European Public Assessment Report on azilsartan medoxomil (Edarbi®) According to the European Bioavailability Association (EPAR), the absolute bioavailability of Azilsartan is approximately 60%. Azilsartan medoxomil potassium salt is practically insoluble in water. That is, Azilsartan has low solubility in water and poor bioavailability, meaning it is not BCS (Biocarbonate of Sulfate). It is a Class II drug. According to the FDA's Edarbi New Drug Application Chemistry Review, Azilsartan medoxomil potassium salt Biopharmaceutical Classification System (BCS) It is class IV, meaning it has low solubility and low permeability in the gastrointestinal tract. This can present difficulties with effective absorption. Because azilsartan and azilsartan medoxomil belong to the biopharmaceutical class, this type To improve the low solubility and low bioavailability of active ingredients. micronization, use of absorption enhancers or auxiliary solvents, active Use of component salts, preparation of solid dispersions and micelles, Inclusion using cyclodextrins, liposomes, emulsions, and microemulsions. Various experiments have been conducted, such as the preparation of complexes. In addition, Nanosuspension to improve the problem of low solubility of active ingredients. Another approach, like this one, has become popular in the pharmaceutical industry. 3 1.98 Pharmaceutical nanocrystals are nanoparticle structures with sizes in the nanometer range. Drug carrier prepared by dispersing drug nanocrystals in a liquid medium. These systems are called "nanosuspensions". Nanosuspensions are improved systems. many advantages such as high resolution, easy scalability, and increased particle surface area It offers / provides. However, when preparing nanosuspensions, thermodynamically... factors to consider include instability, clustering, physical instability, and dispersion. There are also some critical points. Physical and functional properties with improved resolution and enhanced bioavailability. Azilsartan medoxomil is chemically stable and easily scalable. There is still a need for a nanosuspension composition. The inventors of the present invention, surprisingly, believe that Azilsartan medoxomil and / or Its pharmaceutically acceptable salts include copovidon, which contains at least one surfactant. containing the substance and at least one pharmaceutically acceptable excipient, and as desired a product with physical and chemical stability and improved solubility They have developed a nanosuspension formulation. The composition of the present invention is unique. not only stable, but also comparable to the reference product Edarbi® tablet. It exhibits a better dissolution profile when compared. Purpose of the Invention The aim of the present invention is to achieve a more advanced version compared to the reference product Edarbi® tablet. Azilsartan medoxomil or its equivalent, which has a good / superior in-vitro dissolution profile. a nanosuspension composition containing pharmaceutically acceptable salts to provide. Another purpose of the present invention is to utilize Azilsartan medoxomil or its pharmaceutical equivalent. acceptable salts include copovidone, at least one surfactant, and at least one a nanosuspension containing pharmaceutically acceptable excipient The goal is to provide the formulation. 4 1.98 Another purpose of the present invention is to utilize Azilsartan medoxomil or its pharmaceutical equivalent. Acceptable substances include salts, copovidone, vitamin E or its derivatives, and fumaric acid. The aim is to provide a nanosuspension formulation containing... Another objective of the present invention is to create a disintegrating Azilsartan medoxomil. The aim is to provide a nanosuspension composition. Another objective of the present invention is to produce Azilsartan that remains physically and chemically stable. The purpose of medoxomil is to provide a nanosuspension composition. Another objective of the present invention is to create a nanocrystal of Azilsartan medoxomil. to provide. Another objective of the present invention is to achieve what is mentioned in the prior art. A nanosuspension formulation of Azilsartan medoxomil that overcomes problems. to provide. Another aim of the present invention is to develop a useful treatment for hypertension, as described above. The goal is to provide a nanosuspension composition, as mentioned. Disclosure of the Invention In one respect, the present invention, a) Azilsartan medoxomil and / or pharmaceutically acceptable salts, b) copovidon, c) at least one surfactant d) at least one pharmaceutically acceptable excipient It provides a nanosuspension composition containing. From another perspective, the present invention, a) Azilsartan medoxomil and / or pharmaceutically acceptable salts, b) copovidon, 1.98 c) at least one surfactant d) at least one pharmaceutically acceptable excipient It provides a nanosuspension composition containing azilsartan medoxomil. Approximately 1% to 10% by weight of the total weight of the nanosuspension composition. It is the amount to be between them. From another perspective, the present invention, a) Azilsartan medoxomil and / or pharmaceutically acceptable salts, b) copovidon, c) at least one surfactant d) at least one pharmaceutically acceptable excipient It provides a nanosuspension composition containing copovidone. Approximately 1% to 20% by weight of the total weight of the nanosuspension composition. It is the amount to be between them. From another perspective, the present invention, a) Azilsartan medoxomil and / or pharmaceutically acceptable salts, b) copovidon, c) at least one surfactant d) at least one pharmaceutically acceptable excipient It provides a nanosuspension composition containing surfactant, Tween 80, ® sodium lauryl sulfate, vitamin E or its derivatives, poloxamer 188 and Soluplus. It is the selection process. From another perspective, the present invention, a) Azilsartan medoxomil and / or pharmaceutically acceptable salts, b) copovidon, c) at least one surfactant d) at least one pharmaceutically acceptable excipient 6 1.98 It provides a nanosuspension composition containing, and is considered pharmaceutically acceptable. available excipients, pH adjusters selected from citric acid and fumaric acid. He is a spy. From another perspective, the present invention, a) Azilsartan medoxomil and / or pharmaceutically acceptable salts, b) copovidon, c) at least one surfactant d) at least one pharmaceutically acceptable excipient It provides a nanosuspension composition containing, and the nanosuspension composition approximately 1% to 10% of Azilsartan medoxomil by weight, based on total weight. The copovidone content should be between 1% and 20%. From another perspective, the present invention, a) Azilsartan medoxomil and / or pharmaceutically acceptable salts, b) copovidon, c) Vitamin E or its derivatives d) fumaric acid It provides a nanosuspension composition containing. From another perspective, the present invention, a) Azilsartan medoxomil and / or pharmaceutically acceptable salts, b) copovidon, c) Vitamin E or its derivatives d) fumaric acid It provides a nanosuspension composition containing. From another perspective, the present invention, a) Azilsartan medoxomil and / or pharmaceutically acceptable salts, b) copovidon, c) Vitamin E tocopherol polyethylene glycol succinate (TPGS), 7 1.98 d) fumaric acid It provides a nanosuspension composition containing. From another perspective, the present invention relates to the total weight of the nanosuspension composition. according to weight, a) 1% to 10% Azilsartan medoxomil and / or its pharmaceutical equivalent acceptable salts, b) 1% to 20% copovidone, c) 0.1% to 5% Vitamin E TPGS and d) 0.1% to 0.5% fumaric acid It provides a nanosuspension composition containing. From another perspective, the particle size of the nanosuspension in the present invention is 100 nm. between 200 nm and 400 nm, preferably between 200 nm and 500 nm, and pH 3.0 to 5.0 It remains stable between them. From another perspective, the present invention is a nanosuspension involving the following steps: It enables the preparation of the composition: a) Fumaric acid is soluble in water. b) Copovidone is added to the solution obtained in step a), c) Vitamin E TPGS is added to the solution obtained in step b), d) Azilsartan medoxomil and / or the solution obtained in step c) is added to the solution. Pharmaceutical acceptable salts are added, e) To obtain a nanosuspension from the suspension obtained in step d). It is then subjected to wet grinding (DynoMill) process. f) Optionally, the nanosuspension obtained in step e), to obtain the solid form of nanocrystals in a fluidized bed device It is sprayed onto mannitol. 8 1.98 From another perspective, the present invention, a) 5% to 40% (w / w) Azilsartan medoxomil or its pharmaceutical equivalent Nanosuspension containing acceptable salts, b) 60% to 95% (w / w) Mannitol It provides nanocrystals containing. From another perspective, the particle size of the nanocrystals in the present invention ranges from 100 nm to 500 nm. between nm, preferably between 200 nm and 400 nm. In another respect, the present invention relates to azilsartan medoxomil and one or more additional components. It provides a pharmaceutical compound containing a nano-component consisting of a therapeutic agent. From another perspective, this invention can be used for drug preparation in the treatment of hypertension. This enables the use of nanocomposition compounds such as those mentioned. Details of one or more applications of the present invention are given below. This is set forth in the statement. Other features, purpose, and advantages of the invention are also detailed. This will be clear from this statement. Detailed Description of the Invention The present invention will be described in more detail here. The term % used here means percentage by weight unless otherwise specified. It is coming. The term "approximately" can indicate a percentage difference from the specified value. Here Numerical ranges as used, whether specifically stated or not, this range It refers to every number and subset of numbers included within it. Furthermore, this numerical... intervals, requests for any number or subset of numbers within that interval. This should be interpreted as providing support for it. 9 1.98 The term "nanocrystal" as used here refers to crystals of any length, width, or height. semiconductors with dimensions in the nanometer range (i.e., less than approximately 1000 nm) It refers to crystals. The invention describes nanocrystals, dots, rods, on a nanoscale. various forms such as bars, nanofibers, nanowires, sheets and similar structures It may include. The particle size of the nanocrystal in the present invention is between 100 nm and 500 nm. between, preferably, 200 nm and 400 nm, and the average particle size. It is measured using dynamic light scattering (DLS). Nanocrystals can be applied using either a bottom-up or top-down method. This can be achieved using one of the (top-down) methods, preferably from above. The top-down method is used. These include, but are not limited to, the following: together, wet milling, high-pressure homogenization or combination It includes technology. In the present invention, the wet grinding method is preferably used. The term "nanosuspension" refers to submicron colloidal dispersions of nanoparticles. refers to stabilizers, co-surfactants, buffers, osmogens and / or carriers. It is stabilized by the addition of nanoparticles. Nanoparticles typically range between 100 nm and 1000 nm. It has dimensions. The particle size of the nanosuspension in the present invention is 100 nm to 250 nm, preferably between 100 nm and 220 nm, and Litesizer 500 (Anton Paar) The average particle size is measured using dynamic light scattering. The term "nanocomposite" refers to nanosuspensions or nanocrystals. The term "Azilsartan medoxomil" used in the present invention includes, but is not limited to, the following: However, azilsartan medoxomil is pharmaceutically acceptable. salts, pharmaceutically acceptable solvates, pharmaceutically acceptable pharmaceutically acceptable hydrates, pharmaceutically acceptable enantiomers, pharmaceutical with acceptable derivatives and pharmaceutically acceptable prodrugs Together, they also include various crystalline and amorphous forms. 1.98 In the present invention, azilsartan medoxomil salt is used, including but not limited to, the following: It contains sodium salt, monopotassium salt, and potassium salt. Preferably, azilsartan. The potassium salt of medoxomil, which is azilsartan, is camedoxomil. In nanosuspension formulation development studies, the active ingredient is usually... Neutral forms of substances are preferred. Salt forms are susceptible to pH changes. Due to the risk of disproportion and aggregation when left undisturbed, grinding methods are suitable for this purpose. It has been shown that there are few suitable candidates. However, the present invention is suitable for pH values ​​between 3.0 and 5.0 between these two points, when stored under refrigerator conditions (5°C ± 3°C), for a period of 3 months. azilsartan medoxomil potassium salt, which has been shown to remain stable throughout the period It provides nanosuspension formulation. In general practice, the existing invention: a) Azilsartan medoxomil and / or pharmaceutically acceptable salts, b) copovidon, c) at least one surfactant d) at least one pharmaceutically acceptable excipient It provides a nanosuspension composition containing. In another application, the existing invention a) Azilsartan medoxomil and / or pharmaceutically acceptable salts, b) copovidon, c) at least one surfactant d) at least one pharmaceutically acceptable excipient It provides a nanosuspension composition containing surfactant Tween 80, ® sodium lauryl sulfate, vitamin E or its derivatives, poloxamer 188 and Soluplus. It is the selection process. In another application, the existing invention a) Azilsartan medoxomil and / or pharmaceutically acceptable salts, b) copovidon, 11 1.98 c) at least one surfactant d) at least one pharmaceutically acceptable excipient It provides a nanosuspension composition containing, and is considered pharmaceutically acceptable. Available excipients include citric acid and fumaric acid, selected as pH adjusting agents. It is the fact that. In another application, nanosuspension composition, the composition of nanosuspension by weight, according to total weight a) 1% to 10% Azilsartan medoxomil and / or its pharmaceutical equivalent acceptable salts, b) 1% to 20% copovidone, c) 0.1% to 5% Vitamin E TPGS and d) 0.1% to 0.5% fumaric acid includes. In one application, the present invention describes a nanosuspension involving the following steps: It enables the preparation of the composition: a) Fumaric acid is soluble in water. b) Copovidone is added to the solution obtained in step a), c) Vitamin E TPGS is added to the solution obtained in step b), d) Azilsartan medoxomil and / or the solution obtained in step c) is added to the solution. Pharmaceutical acceptable salts are added, e) To obtain a nanosuspension from the suspension obtained in step d). It is then subjected to wet grinding (DynoMill) process. f) Optionally, the nanosuspension obtained in step e), to obtain the solid form of nanocrystals in a fluidized bed device It is sprayed onto mannitol. Surfactants include, but are not limited to, Tween 80, sodium lauryl sulfate, E vitamin or its derivatives, poloxamer 188 and Soluplus® and their mixtures includes. 12 1.98 Pharmaceutical acceptable excipients include, but are not limited to, the following: together with pH adjusting agents, and pH adjusting agents are not limited to these. It does not contain, but includes, citric acid, fumaric acid, and mixtures thereof. In another application, the present invention could be used to create a nanosuspension composition, also known as a... or contains more pharmaceutically acceptable excipients. Although the excipients used in the present invention are well known, the technique... These are auxiliary substances traditionally used by experts. Pharmaceuticals Depending on the chosen dosage form of the composition, pharmaceutical experts in the field of medicine It will be able to select suitable excipients that can be accepted as such. Pharmaceutical excipients: stabilizers, co-surfactants, buffers, osmogens and can be selected from the carrier. The carrier is Azilsartan, used to obtain a solid form of the nanosuspension. It is used in medoxomil nanosuspension. The resulting nanosuspension... solid form, spray drying, freeze-drying obtained using one of the following methods: drying or wet granulation. It can be used as a carrier. The carrier may include, but is not limited to, lactose, mannitol, sucrose, It contains trehalose and maltodextrin. Preferably, it contains mannitol. In another application, the existing invention a) 5% to 40% (w / w) Azilsartan medoxomil or its pharmaceutical equivalent Nanosuspension containing acceptable salts, b) 60% to 95% (w / w) Mannitol It provides nanocrystals containing. The invention also suggests that the nano-composition in question is useful in the treatment of hypertension. It relates to its use in the preparation of medicines. Furthermore, the pharmaceutical composition of the present invention is widely used in industry. With the use of equipment and techniques, it is very suitable for commercial-scale production. 13 1.98 The following examples are not intended to limit the scope of the invention and are included below. It aims to demonstrate the scope of the invention. Examples Example 1: Preparation of azilsartan medoxomil nanosuspension composition Table-1 No. Components % a / a 1 Azilsartan Medoxomil (potassium salt) 4 2 Copovidone 5 3 Vitamin E TPGS 0.25 4 Fumaric acid 0.4 deionized water km Preparation Process a) Fumaric acid was dissolved in water, b) Copovidone was added to the solution obtained in step a), c) Vitamin E TPGS was added to the solution obtained in step b), d) The solution obtained in step c) is added as azilsartan medoxomil potassium salt. added, e) The suspension obtained in step d) is used to obtain a nanosuspension. It was subjected to wet grinding (DynoMill) process. 14 1.98 Example 2: Stability of Azilsartan Medoxomil nanosuspension at 5°C±3°C data. Table 2 Limit Starting Month 1 Month 3 Particle Size <500 219.6 ± 1.81 218.4 ± 1.69 223.3 ± 1.44 (nm) PDI < 0.3 0.173 ± 0.026 0.16 ± 0.013 0.193 ± 0.022 Zeta Potential > ±20 mV -32.2 ± 0.8 -31.1 ± 0.1 -30.5 ± 0.8 (mV) Quantitative Determination (%) 95-105% 100.37 ± 0.19 100.09 ± 0.01 101.8 ± 1.4 pH 3-5 4.71 4.73 4.75 PDI: Polydispersity Index Particle size, PDI, Zeta Potential, Quantity determination and pH were measured during the stability period. no significant changes and all values ​​are within the defined range It has been observed that when the nanosuspension is stored in the refrigerator (5°C ± 3°C), 3 It has been shown to remain stable over a period of months. Example-3 Azilsartan Medoxomil Potassium salt (API), reference product Edarbi®, Dissolution data for Sample 1. Table 3 pH 6.8 Phosphate Buffer Time Capsule Reference Product Sample-1 stuffed Edarbi® Nanosuspension API 3.0 min 30.26 71.48 29.28 34.32 72.96 min 34.53 37.41 73.45 min 34.94 39.85 73.1 min 38.05 43.82 80.42 min 1.98 45 min 41.23 46.74 79.83 60 min 43.56 46.50 78.38 Table 4: 0.1 N HCl Time Capsule Reference Product Sample-1 stuffed Edarbi® Nanosuspension API 1.28 23.25 78.57 min 3.3 min 25.23 80.24 min 4.04 min 28.82 78.29 4.65 min 31.12 75.03 min 5:44 34:12 74:14 45 min 6.7 36.97 71.86 60 min 7.45 38.69 68.69 The test product in Example 1 (Nanosuspension containing 40 mg of active ingredient), Azilsartan Medoxomil Potassium Salt (API, 40 mg Azilsartan Medoxomil) (equivalent) and dissolution of the reference product Edarbi® 40 mg, using standard USP apparatus II. Using a pedal, at 50 rpm, in 900 ml pH 6.8 phosphate buffer and 0.1 N HCl This was carried out. Drug release was determined using UV spectroscopy. Table-3 and From the above dissolution data given in Table-4, Sample 1's API and reference It was observed that the product showed better dissolution results compared to others. 16 1.98 Example 4: Preparation of Nanocrystals Table-5 No. Components mg / nanosuspension Azilsartan medoxomil 1 42.68 potassium salt 2 Kopovidone 53.35 3 TPGS 2.66 4 Fumaric acid 4.26 deionized water qs Total weight of nanosuspension: 102.95 Wet milling 6 Mannitol 426.8 Fluidized bed granulation Total Weight 529.75 Preparation Process a) Fumaric acid was dissolved in water, b) Copovidone was added to the solution obtained in step a), c) Vitamin E TPGS was added to the solution obtained in step b), d) The solution obtained in step c) is added as azilsartan medoxomil potassium salt. added, e) The suspension obtained in step d) is used to obtain a nanosuspension. It was subjected to wet grinding (DynoMill) process. f) The nanosuspension obtained in step e) takes the solid form of nanocrystals. To obtain this, it was sprayed onto mannitol in a fluidized bed device. 17 1.98 Example 5 - Comparison of nanosuspensions and nanocrystals Table-6 Limit Nanosuspension Nanocrystals Particle Size (nm) <500 219.6 ± 1.81 254.2 ± 5.19 PDI < 0.3 0.173 ± 0.026 0.244 ± 0.015 Zeta Potential (mV) > ±20 mV -32.2 ± 0.8 -30.2 ± 0.1 PDI: Polydispersity Index Particle size, PDI, and Zeta potential of nanosuspensions and nanocrystals. No significant changes were observed in the results, and all values ​​remained as defined. It is in December. 18

Claims

1. a. Azilsartan medoxomil and / or pharmaceutically acceptable salts, b. Copovidon, c. at least one surfactant d. at least one pharmaceutically acceptable excipient It is a nanosuspension composition containing...

2. According to claim 1, it is a nanosuspension composition, and the nanosuspension is... It contains azilsartan medoxomil salt.

3. A nanosuspension composition according to Claim 1 or Claim 2, consisting of salts. It is a potassium salt.

4. According to claim 1, it is a nanosuspension composition, and the nanosuspension is... The particle size should be between 200 nm and 400 nm.

5. A nanosuspension composition according to claim 1, where the surfactant is Tween 80, sodium lauryl sulfate, vitamin E or its derivatives, poloxamer 188 and It is chosen from Soluplus®.

6. A nanosuspension composition according to Claim 1 or Claim 5, containing surfactant. Vitamin E is TPGS.

7. It is a nanosuspension composition according to Claim 1 and is considered pharmaceutical. The usable auxiliary substance is a pH adjusting agent.

8. A nanosuspension composition according to claim 1 or claim 7, pH The adjusting agent is chosen from citric acid and fumaric acid.

9. A nanosuspension composition according to claim 8, with pH adjusting agent It is fumaric acid. 19 1.98 10. According to claim 1, it is a nanosuspension with a pH of 3.0 to 5.0 It is stable between them.

11. A nanosuspension composition according to any of the previous requirements, by weight, according to the total weight of the nanosuspension composition, a) 1% to 10% Azilsartan medoxomil and / or its pharmaceutical equivalent acceptable salts, b) 1% to 20% copovidone, c) 0.1% to 5% Vitamin E TPGS and d) 0.1% to 0.5% fumaric acid It includes.

12. A nanosuspension composition according to any of the previous requirements. a. Fumaric acid is soluble in water. b. Copovidone is added to the solution obtained in step a), c. Vitamin E TPGS is added to the solution obtained in step b), d. Azilsartan medoxomil and / or the solution obtained in step c) is added to the solution. Pharmaceutical acceptable salts are added, The suspension obtained in step d) is used to produce a nanosuspension. It is subjected to a wet grinding process in order to do this, f. Optionally, the nanosuspension obtained in step e), fluidized bed for obtaining solid form of nanocrystals It is sprayed onto mannitol in the device, It includes the steps.

13. According to claim 12, nanocrystals, a) 5% to 40% (w / w) Azilsartan Medoxomil or its pharmaceutical equivalent nanosuspension containing acceptable salts, b) 60% to 95% (w / w) Mannitol It includes. 1.98 14. A nanocomposition composition according to any of the previous requirements. It is used in the treatment of hypertension. 21