An allisartan isoproxil pharmaceutical composition as well as preparation method and application thereof

Abstract

The invention provides an allisartan medoxomil pharmaceutical composition which is high in loading capacity, good in dissolution performance and good in stability, and the pharmaceutical composition contains carrier materials of copovidone and cross-linked povidone and is prepared by adopting a hot melt extrusion process.

Description

(19) State Intellectual Property Office (12) Invention Patent Application (10) Application Publication Number (43) Application Publication Date (21) Application Number 202511422360.5 (22) Application Date 2025.09.29 (66) Domestic Priority Data 202411389352.0 2024.09.30 CN (71) Applicant Shenzhen Xinlitai Pharmaceutical Co., Ltd. Address 518017, Guangdong Province, Futian District, Fubao Street, Fubao Community, Hongliu Road 289 Digital Peninsula 4th Floor, Area A Applicant Huizhou Xinlitai Pharmaceutical Co., Ltd. (72) Inventors Zhong Yiwen Ye Guanhao Liang Xi Zhong Xiaoyu Huang Wulue Fu Yating (51) Int.Cl. A61K 9 / 14 (2006.01) A61K 31 / 4178 (2006.01) A61K 47 / 32 (2006.01) A61K 9 / 28 (2006.01) A61P 9 / 12 (2006.01) A61P 9 / 00 (2006.01) A61P 9 / 10 (2006.01) A61P 9 / 04 (2006.01) A61P 25 / 00 (2006.01) A61P 13 / 12 (2006.01) A61P 27 / 02 (2006.01) (54) Invention Title: An Alisartan Ester Pharmaceutical Composition and Its Preparation Method and Application (57) Abstract: This invention provides an alisartan ester pharmaceutical composition with high loading capacity, good dissolution performance, and good stability. The pharmaceutical composition contains copovidone and cross-linked povidone as carrier materials and is prepared by hot melt extrusion process. Claims (1 page), Description (8 pages), Drawings (2 pages), CN 121015569 A 2025.11.28 CN 1 21 01 55 69 A 1. An alisartan medoxomil pharmaceutical composition, characterized in that the pharmaceutical composition contains alisartan medoxomil, copovidone, and cross-linked povidone as carrier materials, prepared by a hot-melt extrusion process, wherein the hot-melt extrudate is a solid dispersion. 2. The alisartan medoxomil pharmaceutical composition according to claim 1, characterized in that, when the mass part of alisartan medoxomil is 1, the mass part of copovidone is 0.3-0.45. 3. The alisartan medoxomil pharmaceutical composition according to claim 1, characterized in that, when the mass part of alisartan medoxomil is 1, the mass part of cross-linked povidone is 0.3-0.45. 4. The alisartan ester pharmaceutical composition according to claim 2, characterized in that, when the mass part of alisartan ester is 1, the mass part of cross-linked povidone is 0.3-0.45.5. The alisartan medoxomil pharmaceutical composition according to any one of claims 1-4, characterized in that it further comprises a flow aid selected from talc, colloidal silica, or a combination thereof. 6. The alisartan medoxomil pharmaceutical composition according to claim 5, characterized in that the flow aid is present in an amount of 0.005-0.01 parts by weight. 7. The alisartan medoxomil pharmaceutical composition according to claim 1, characterized in that it is prepared by a hot-melt extrusion process. 8. An alisartan medoxomil pharmaceutical composition, characterized in that it comprises a solid dispersion of the alisartan medoxomil pharmaceutical composition according to any one of claims 1-7, and one or more pharmaceutical excipients. 9. The alisartan medoxomil pharmaceutical composition according to claim 8, characterized in that the pharmaceutical excipient comprises one or a mixture of two or more of a disintegrant, a binder, a filler, a flow aid, and a lubricant. 10. The alisartan medoxomil pharmaceutical composition according to claim 9, characterized in that: the disintegrant is one or more of croscarmellose sodium, croscarmellose povidone, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, starch, pregelatinized starch, etc.; and / or the binder is one or more of hydroxypropyl methyl cellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, povidone, starch paste, gelatin; and / or the filler is one or more of lactose, mannitol, dextrin, microcrystalline cellulose, starch, pregelatinized starch, calcium sulfate, calcium phosphate, dicalcium phosphate, etc.; and / or the flow aid is selected from one or more of talc, colloidal silica, etc.; and / or the lubricant is one or more of magnesium stearate, micronized silica, talc, stearic acid, etc. Claims 1 / 1 Page 2 CN 121015569 A A drug composition of alisartan ester and its preparation method and application Technical Field

[0001] This invention belongs to the field of pharmaceutical preparations, and in particular, this invention relates to a drug composition of alisartan ester and its preparation method and application. Background Art

[0002] Alisartan ester (CAS: 947331-05-7), chemically named 2-butyl-4-chloro-1-[2'-(1H-tetrazol-5-yl)-1,1'-biphenyl-methyl]-imidazol-5-carboxylic acid, 1-[(isopropoxy)-carbonyloxy]-methyl ester, is a novel angiotensin II receptor antagonist. Chinese patent CN200680000397.8 discloses the structural formula of the alisartan ester compound. Alisartan ester has low toxicity and a better antihypertensive effect than similar products (such as losartan). It exerts its antihypertensive effect by generating an active metabolite (EXP3174) in vivo. Alisartan medoxomil is an ester derivative of EXP3174. It has low solubility in water, and formulations obtained using conventional methods are difficult to meet clinical needs.

[0003]

[0004] Chinese Patent CN200880001668.0 discloses a series of formulations containing alisartan ester, wherein Examples D1 to D6 disclose an alisartan ester solid dispersion and its preparation method, which uses a fluidized bed top spray method to prepare the alisartan ester solid dispersion. This method is complex, and to avoid excessive organic solvent residue, a relatively long drying time is usually required, which is not the optimal process for preparing solid dispersions.

[0005] Chinese Patents CN 2 01 51 0 2 5 4 0 2 0 .6 and CN 2 01 5 1 0 3 3 4 4 9 8 .X further optimize the formulation based on Patent CN200880001668.0, providing two improved alisartan ester solid dispersions. However, their technical improvements do not involve changes to the preparation process. Therefore, this method still suffers from the drawbacks of the fluidized bed top spray method, which is complex and has a relatively long processing time.

[0006] Chinese Patent CN201510287997.8 discloses a nano-suspension prepared by effervescent method. Patent Example 8 discloses a method for preparing alisartan ester nano-suspension containing povidone and sodium dodecyl sulfate (SDS). However, due to the properties of alisartan ester, the preparation of nanoparticles by effervescent method has certain quality fluctuations, making its process stability insufficient to support industrial production. In addition, this method uses a large number of pharmaceutical excipients (povidone, SDS, etc.), and does not achieve optimal combination of raw materials and excipients, resulting in a low drug loading per unit mass of internal phase particles, failing to achieve optimal formulation and process.

[0007] Chinese Patent CN201610373232.0 discloses an alisartan ester pharmaceutical composition, which uses a grinding process to disperse alisartan ester into nano-sized particles in the pharmaceutical composition. However, this method failed to achieve better in vitro dissolution of alisartan ester than described in the specification (page 1 / 8, CN 121015569 A). CN201610379945.8 discloses an alisartan ester solid dispersion prepared by a hot melt extrusion process. In this process, when the mass fraction of alisartan ester is 1, the mass fraction of the carrier material is 0.8–2.5, preferably 1–25. This method uses a relatively large amount of binder.

[0008] CN202210060985.1 discloses a compound antihypertensive drug composition, which comprises the active ingredients alisartan medoxomil and / or its salts, indapamide and / or its salts. An example alisartan medoxomil monotherapy formulation contains 120 mg alisartan medoxomil, 58 mg copovidone, and 115 mg crospovidone, prepared using a fluidized bed process. This process has a long time to process solvent residue. Upon investigation, this formulation is not suitable for hot-melt extrusion processes, resulting in severe venting problems and discontinuous extruded particles.

[0009] Therefore, increasing the content of active ingredients in a formulation while ensuring its stability and dissolution is a technical problem that has not been solved by existing technologies. Starting from the shortcomings of existing technologies, this invention has discovered a new alisartan ester solid dispersion through numerous experiments. This dispersion has the characteristics of high drug loading, good dissolution performance, and good stability. Summary of the Invention

[0010] The purpose of this invention is to overcome the shortcomings of existing technologies. While ensuring the stability and dissolution of the formulation, by adjusting the type and proportion of the carrier material, the content of active ingredients in the solid dispersion is increased, thus discovering a high-load alisartan ester solid dispersion. The drug loading of this solid dispersion is higher than that of existing technologies, and the drug composition containing this solid dispersion has good dissolution performance and good stability, meeting the requirements for clinical drug use.

[0011] It is well known in the art that solid dispersions are used to highly disperse active ingredients in a carrier material in the form of microcrystals, amorphous or molecular forms through formulation methods, thereby improving drug dissolution. Drug loading, or drug loading amount, refers to the amount of active ingredient loaded per unit mass of carrier in a solid dispersion. Generally, increasing the amount of carrier material in a solid dispersion helps improve drug dissolution. However, when the amount of carrier increases to a certain extent, it will no longer significantly improve drug dissolution. In addition, excessive carrier usage increases the cost of the drug and the weight of the unit formulation. Usually, to achieve the solubility enhancement effect, the mass ratio of active ingredient to carrier material in a solid dispersion is controlled at 1:5 to 20. However, for specific drugs, there is still room for further improvement in the drug loading of the solid dispersion.

[0012] Therefore, in the research process of solid dispersion preparation, it is necessary to study the optimal combination and ratio of active drug and carrier material to achieve the purpose of promoting drug dissolution while controlling the weight of the dosage form, thereby optimizing the clinical dosage and antihypertensive effect and improving medication compliance. However, it is difficult to obtain a solid dispersion with high dissolution and high drug loading. Regarding the selection of the ratio, if the drug loading is too high, the amount of carrier used is too small, so that the active ingredient cannot be in a stable and highly dispersed state, and thus a solid dispersion cannot be obtained, which is manifested as the dissolution not meeting the standard. In addition, the type of carrier material can also affect the dispersion effect of the active ingredient.

[0013] The above-mentioned beneficial effects of the solid dispersion of the present invention are achieved by the following technical means:

[0014] An alisartan ester pharmaceutical composition, wherein the pharmaceutical composition contains alisartan ester, copovidone and cross-linked povidone as carrier materials, and is prepared by hot melt extrusion process, wherein the hot melt extrudate is a solid dispersion.

[0015] Specifically, the key technology of the present invention lies in the carrier materials being copovidone and cross-linked povidone. Copovidone (PVP / VA) is a water-soluble organic polymer compound, a linear copolymer of N-vinylpyrrolidone (NVP) and vinyl acetate (VA). Commonly available copovidones include PVP-VA64, Kollidon VA64, and Plasdone S-630. Cross-linked povidone is a water-insoluble synthetic cross-linked N-vinyl-2-pyrrolidone homopolymer.

[0016] More specifically, as a preferred embodiment of the present invention, when the mass fraction of alisartan ester is 1, the mass fraction of copovidone in the solid dispersion is 0.3-0.45. Instructions for Use, Page 2 / 8, CN 121015569 A

[0017] Those skilled in the art typically use copovidone as a solid dispersion carrier material and believe that a ratio of at least 0.8 is necessary to effectively achieve dissolution. For example, in prior art CN201610379945.8, when the mass fraction of alisartan ester is 1, the mass fraction of the carrier material is 0.8 to 2.5, preferably 1 to 2. Ashland's guidelines for using povidone and copovidone Plasdone specify that the recommended dosage of copovidone as a solid dispersion carrier is generally 3 times the amount of drug. However, through extensive research, the applicant has discovered that for alisartan ester compounds, using a small amount of copovidone carrier material to prepare a solid dispersion can also achieve the desired dissolution effect, significantly reducing the amount of carrier material used and effectively controlling tablet weight. Furthermore, the applicant unexpectedly discovered that the preferred application range for preparing hot-melt extruded granules is a ratio of copovidone to the active pharmaceutical ingredient between 0.3:1 and 0.45:1. In the implementation examples, when the ratio is 0.5:1 or 0.625:1, in vitro dissolution slows down, resulting in non-compliance.

[0018] More specifically, as a preferred technical solution of the present invention, when the mass fraction of alisartan ester is 1, the mass fraction of cross-linked povidone in the solid dispersion is 0.3-0.45.

[0019] The selection of disintegrants is usually indispensable for solid dispersions to achieve suitable dissolution effects. Generally, the more disintegrant used, the better the dissolution effect. Moreover, in the fluidized bed solid dispersion process, the applicant's previous research found that formulations containing copovidone require a cross-linked povidone amount equivalent to that of alisartan ester to meet the disintegrant effect. However, the applicant's research unexpectedly revealed that the optimal ratio of cross-linked polyvinylpyrrolidone to the active pharmaceutical ingredient (API) for preparing hot-melt extruded granules is between 0.3:1 and 0.45:1. In the implementation case, when the ratio was 0.25:1, in vitro dissolution was slow, resulting in non-compliance; when the ratio was 0.5:1, the extrusion process was unsuitable, leading to severe venting problems and discontinuous extruded granules.

[0020] As a technical solution of the present invention, it further includes a flow aid, which is selected from any one or a combination of talc, colloidal silica (fumed silica). When the mass part of alisartan ester is 1, the mass part of the flow aid is 0.005-0.01. This can effectively ensure the uniform mixing and flowability of the solid dispersion.

[0021] Another object of the present invention is to provide a method for preparing an alisartan ester solid dispersion, wherein the alisartan ester solid dispersion is prepared by a hot melt extrusion process, and the extrusion temperature of the hot melt extrusion process is 160±10℃.

[0022] Another object of the present invention is to provide an alisartan ester pharmaceutical composition, wherein the pharmaceutical composition is composed of the above-mentioned alisartan ester solid dispersion and pharmaceutical excipients.

[0023] As a technical solution of the present invention, the pharmaceutical excipients of the alisartan ester pharmaceutical composition include one or a mixture of two or more of the following: disintegrant, binder, filler, flow aid, and lubricant.

[0024] In a preferred embodiment of the present invention, the disintegrant is one or more of the following: croscarmellose sodium, croscarmellose povidone, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, starch, pregelatinized starch, etc.

[0025] In a preferred embodiment of the present invention, the binder is one or more of the following: hydroxypropyl methylcellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, povidone, starch paste, gelatin, etc.

[0026] In a preferred embodiment of the present invention, the filler is one or more of the following: lactose, mannitol, dextrin, microcrystalline cellulose, starch, pregelatinized starch, calcium sulfate, calcium phosphate, calcium hydrogen phosphate, etc.

[0027] In a preferred embodiment of the present invention, the flow aid is selected from one or more of the following: talc, colloidal silica, etc.

[0028] In a preferred embodiment of the present invention, the lubricant is one or more of the following: magnesium stearate, micronized silica gel, talc, stearic acid, etc.

[0029] As a technical solution of the present invention, the amount of solid dispersion and newly added pharmaceutical excipient in the alisartan ester pharmaceutical composition can be appropriately adjusted, for example: the mass ratio of disintegrant is 1:0.02-0.20; the mass ratio of solid dispersion to binder in the pharmaceutical composition is 1:0.01-0.05; the mass ratio of solid dispersion to filler in the pharmaceutical composition is 1:0.02-0.20; the mass ratio of solid dispersion to glidant in the pharmaceutical composition is 0.005-0.02; the mass ratio of solid dispersion to lubricant in the pharmaceutical composition is 0.005-0.02.

[0030] The present invention further provides a method for preparing alisartan ester solid dispersion by hot melt extrusion, the method comprising the following steps:

[0031] (1) mixing alisartan ester and excipients uniformly to form a physical mixture;

[0032] (2) adding the physical mixture in step (1) to a hot melt extruder, and extruding a strip-shaped product after melting;

[0033] (3) cooling the strip-shaped product obtained in step (2) and then pulverizing it to obtain a solid dispersion containing alisartan ester.

[0034] The present invention further provides a method for preparing an alisartan ester pharmaceutical composition, the method comprising the following steps:

[0035] (4) mixing the solid dispersion with pharmaceutical excipients uniformly, compressing to obtain a tablet, and then coating with a film to obtain an alisartan ester pharmaceutical composition.

[0036] The alisartan ester pharmaceutical composition of the present invention can be used for the treatment of hypertension and its complications. Preferably, the alisartan ester pharmaceutical composition can be used for the treatment of mild, moderate and severe essential hypertension. The hypertension complications refer to conditions caused by hypertension, including: cardiac complications such as left ventricular hypertrophy, angina pectoris, myocardial infarction, heart failure, etc.; stroke such as hemorrhagic stroke, ischemic stroke, hypertensive encephalopathy, etc.; hypertensive kidney damage such as slowly progressive arteriolar nephrosclerosis, malignant arteriolar nephrosclerosis, chronic renal failure, etc.; ophthalmic diseases such as retinal arteriosclerosis, fundus changes, etc.

[0037] Compared with the prior art, the present invention has the following outstanding advantages and beneficial effects:

[0038] 1. It provides an alisartan ester solid dispersion, which reduces the amount of binder and disintegrant used and effectively controls the tablet weight;

[0039] 2. It provides an alisartan ester pharmaceutical composition containing the alisartan ester solid dispersion described in the present invention, which has the characteristics of good dissolution performance and good stability.

[0040] Figure 1: Schematic diagram of slow dissolution (30 min) using the experimental method of the present invention;

[0041] Figure 2: Schematic diagram of smoothness of extrudate using the experimental method of the present invention;

[0042] Figure 3: Schematic diagram of XRPD diffraction of solid dispersion containing crystals using the experimental method of the present invention. Detailed Description of Embodiments

[0043] The present invention will be further described in detail below with reference to embodiments, but the embodiments of the invention are not limited thereto.

[0044] Dissolution determination method of the present invention:

[0045] Dissolution method: Paddle method (second method)

[0046] Rotation speed: 50 rpm

[0047] Dissolution medium: pH 6.8 phosphate buffer

[0048] Temperature: 37.0 ± 0.5℃

[0049] Sampling time: 30 min

[0050] Dissolution medium volume: 900 ml Instruction manual 4 / 8 pages 6 CN 121015569 A

[0051] XRPD determination method:

[0052] X-ray powder diffraction (XRPD), the XRPD pattern was acquired on an X-ray powder diffractometer manufactured by PANalytical, and the scanning parameters are as follows:

[0053] Parameter Instrument model Empyrean Optical path module BBHD Anode Material Cu Voltage, current 45kV, 40mA Diverging slit 1 / 4° Anti-scattering slit 1° Sola slit 0.04rad Scanning mode Continuous Scan range (°2Theta) 3-40 Scan time per step (s) 30.09 Scan step size (°2Theta) 0.026

[0054] Examples A1-A9

[0055]

[0056]

[0057] Preparation of solid dispersion:

[0058] (1) Alisartan ester and excipients PVP-VA64, crosslinked polyvinylpyrrolidone and colloidal silica are mixed evenly to form a physical mixture;

[0059] (2) The physical mixture in step (1) is added to a hot melt extruder (165°C) and melted and extruded into a strip product;

[0060] (3) The strip product obtained in step (2) is cooled and pulverized to obtain a solid dispersion containing alisartan ester drug.

[0061] Wherein:

[0062] Formulation A3 (crosslinked polyvinylpyrrolidone ratio of 0.28, <0.3) and Formulation A9 (copolyvinylpyrrolidone ratio of 0.47, >0.45) both dissolve slowly, as shown in Figure 1;

[0063] Formulation A6 (crosslinked polyvinylpyrrolidone ratio of 0.47, >0.45) is not suitable for extrusion process, resulting in material run-out, as shown in Figure 2, page 5 / 8 of the specification, CN 121015569 A;

[0064] Formulation A7 (copolyvinylpyrrolidone ratio of 0.28, <0.3) shows crystallization in XRPD analysis, as shown in Figure 3;

[0065] Other preferred formulations have good dissolution, are in an amorphous state, and have good stability.

[0066] Examples B1-B12

[0067] Internal formulation:

[0068]

[0069]

[0070] External formulation:

[0071]

[0072] Preparation:

[0073] 1. Preparation of solid dispersion

[0074] (1) Alisartan ester and excipients PVP-VA64, crosslinked povidone and colloidal silica are mixed evenly to form a physical mixture;

[0075] (2) The physical mixture in step (1) is added to a hot melt extruder (165°C), and after melting and extrusion, a strip product is obtained;

[0076] (3) The strip product obtained in step (2) is cooled and pulverized to obtain a solid dispersion containing alisartan ester.

[0077] 2. Preparation of pharmaceutical composition

[0078] The solid dispersion is mixed evenly with the remaining materials, compressed into tablets to obtain uncoated tablets, and then coated with a film to obtain an alisartan ester pharmaceutical composition. Instructions for Use, Page 6 / 8, CN 121015569 A

[0079] Wherein:

[0080] Formulation B1 (crosslinked polyvinyl acetate ratio of 0.25, <0.3), Formulation B3 (copolyvinyl acetate ratio of 0.625, >0.45), and Formulation B4 (copolyvinyl acetate ratio of 0.5, >0.45) all dissolve slowly;

[0081] Formulations B2 and B7 (crosslinked polyvinyl acetate ratio of 0.5, >0.45) are not suitable for extrusion processes, resulting in severe venting problems and discontinuous extruded particles;

[0082] Preferred formulations such as B5, B6, B8-B12 have good disintegration and dissolution, good stability, and exhibit excellent in vivo exposure effects.

[0083] Comparative Example 1--CN201610379945.8 Example 4

[0084] Formulation:

[0085]

[0086] Preparation of solid dispersion:

[0087] (1) Alisartan ester and excipients are mixed evenly to form a physical mixture;

[0088] (2) The extrusion temperature is set to 120℃. After the temperature stabilizes, the physical mixture in step (1) is added to the hot melt extruder at a uniform speed to extrude strip extrudate;

[0089] (3) The strip extrudate obtained in step (2) is cooled and then crushed through a 60-mesh sieve to obtain alisartan ester drug solid dispersion.

[0090] After the drug composition is prepared using the external formulation of Examples 1-12, the disintegration rate is slow. If a disintegrant is further added to the internal formulation, not only will the dissolution be slower, but the tablet weight will also increase significantly.

[0091] Comparative Example 2 – CN202210060985.1 Example 3

[0092] Formulation:

[0093]

[0094] The preparation process is the same as in Examples B1-B12.

[0095] The extrusion process of this formulation is not suitable, resulting in serious exhaust problems and discontinuous extruded particles.

[0096] Comparative Example 3, Specification, Pages 7 / 8, CN 121015569 A

[0097] When using Formula 5, the proportion of copovidone binder is 0.2 (48mg), the formula has dissolution problems.

[0098] Comparative Example 4

[0099] Long-term stability test of preferred embodiment of the present invention:

[0100]

[0101] As can be seen from the table above, the preferred formula of the present invention has good dissolution stability.

[0102] Comparative Example 5

[0103] (1) Experimental materials

[0104] SD rats: male, 180-250g, purchased from Guangdong Vital River Laboratory Animal Technology Co., Ltd.

[0105] Reagents: DMSO (dimethyl sulfoxide), HPMC are commercially available.

[0106] Instruments: LC-MS / MS (SCIEX, TripleQuad5500+ triple quadrupole mass spectrometer).

[0107] (2) Experimental Methods

[0108] Different formulations of alisartan ester solid dispersion powder were weighed and administered by gavage with 1% HPMC as solvent. Venous blood was collected at 15 min, 30 min, 1 h, 2 h, 5 h, 7 h, and 24 h.

[0109] A certain amount of EXP3174 was accurately weighed, dissolved in DMSO, and used as a stock solution. Blank plasma was added to prepare plasma samples of different concentrations, and a standard curve was established.

[0110] The aforementioned venous blood plasma was analyzed by LC-MS / MS to determine the concentration of EXP3174.

[0111] 3. Data Processing

[0112] After detecting the blood concentration of EXP3174 by LC-MS / MS, the pharmacokinetic parameters were calculated using WinNonlin software and the non-compartmental model method.

[0113] The experimental results are as follows:

[0114]

[0115] As can be seen from the table above, the preferred formulation of this invention shows better in vivo exposure.

[0116] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be equivalent substitutions and shall be included within the protection scope of the present invention.Instruction manual, page 8 / 8, CN 121015569 A, Figure 1, Figure 2; Instruction manual, Figure 1 / 2, page 11, CN 121015569 A, Figure 3; Instruction manual, Figure 2 / 2, page 12, CN 121015569 A. Abstract: The present invention provides an Allisartan Isoproxil pharmaceutical composition with high loading capacity, good dissolution performance, and good stability. The pharmaceutical composition contains carrier materials of PVP / VA and PVPP and is prepared by a hot melt extrusion process.

Claims

1. An alisartan medoxomil pharmaceutical composition, characterized in that, The pharmaceutical composition contains alisartan ester, copovidone, and cross-linked povidone as carrier materials, and is prepared by hot melt extrusion process. The hot melt extrudate is a solid dispersion.

2. The alisartan medoxomil pharmaceutical composition according to claim 1, characterized in that, When the mass fraction of alisartan ester in the solid dispersion is 1, the mass fraction of copovidone is 0.3-0.

45.

3. The alisartan medoxomil pharmaceutical composition according to claim 1, characterized in that, When the mass fraction of alisartan ester in the solid dispersion is 1, the mass fraction of cross-linked polyvinyl ketone is 0.3-0.

45.

4. The alisartan medoxomil pharmaceutical composition according to claim 2, characterized in that, When the mass fraction of alisartan ester in the solid dispersion is 1, the mass fraction of cross-linked polyvinyl ketone is 0.3-0.

45.

5. The alisartan medoxomil pharmaceutical composition according to any one of claims 1-4, characterized in that, It further contains a flow aid selected from talc, colloidal silica, or a combination thereof.

6. The alisartan medoxomil pharmaceutical composition according to claim 5, characterized in that, The mass fraction of the gliding agent is 0.005-0.

01.

7. The alisartan medoxomil pharmaceutical composition according to claim 1, characterized in that, The alisartan ester pharmaceutical composition was prepared by a hot melt extrusion process.

8. An alisartan medoxomil pharmaceutical composition, characterized in that, The solid dispersion comprising the alisartan ester pharmaceutical composition according to any one of claims 1-7, and one or more pharmaceutical excipients.

9. The alisartan medoxomil pharmaceutical composition according to claim 8, characterized in that, The pharmaceutical excipients comprise one or more of the following: disintegrants, binders, fillers, flow aids, and lubricants.

10. The alisartan medoxomil pharmaceutical composition according to claim 9, characterized in that, The disintegrant is one or a mixture of croscarmellose sodium, croscarmellose, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, starch, pregelatinized starch, etc. And / or the adhesive is one or more of hydroxypropyl methylcellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, povidone, starch paste, and gelatin; And / or the filler is one or more of lactose, mannitol, dextrin, microcrystalline cellulose, starch, pregelatinized starch, calcium sulfate, calcium phosphate, and dicalcium phosphate; And / or the flow aid is selected from one or more of talc, colloidal silica, and a mixture thereof; And / or the lubricant is one or more of magnesium stearate, micronized silica gel, talc, and stearic acid.

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