Preparation method and dissolution rate detection method of amoxicillin capsule

Abstract

The invention relates to the technical field of amoxicillin capsules, and discloses a preparation method and a dissolution rate detection method of an amoxicillin capsule, dry granulation is adopted to control the particle size range of raw materials, under the condition that a disintegrating agent is not used, the dissolution rate of the capsule is improved by adjusting the dosage of magnesium stearate, and the dissolution rate of the capsule is increased by adjusting the dosage of magnesium stearate. And the purpose that the dissolution behavior of the product is similar to that of the original development agent is achieved. Compared with the prior art, the capsule provided by the invention is simpler on the premise of meeting the quality requirements of medicines, the volume of the capsule is reduced, and the compliance of clinical use is improved.

Description

Technical Field

[0001] The invention relates to the technical field of amoxicillin capsules, and in particular to a preparation method and a dissolution detection method of an amoxicillin capsule. Background Art

[0002] Amoxicillin, also known as amoxicillin, is one of several semi-synthetic derivatives of 6-aminopenicillanic acid. It is a semi-synthetic broad-spectrum penicillin drug that introduces a para-hydroxyl group on the side chain benzene ring of ampicillin. Amoxicillin can be used to treat acute bacterial sinusitis, acute otitis media, acute streptococcal tonsillitis and pharyngitis, acute exacerbation of chronic bronchitis, community-acquired pneumonia, acute cystitis, asymptomatic bacteriuria during pregnancy, acute pyelonephritis, typhoid and paratyphoid fever, dental abscesses and disseminated cellulitis, prosthetic joint infections, Helicobacter pylori infections, and Lyme disease in adults and children; it can also prevent endocarditis.

[0003] Currently, commercially available amoxicillin capsules are often granulated with disintegrants such as cross-linked polyvinylpyrrolidone and sodium carboxymethyl starch to achieve rapid disintegration and rapid dissolution, but there are problems such as high polymer impurities, poor stability, capsule burst release caused by uneven mixing of raw materials and disintegrants, and large individual dissolution differences, which may reduce the dissolution rate of amoxicillin capsules. The present invention ensures a high dissolution rate of amoxicillin by adjusting the particle size of the raw material amoxicillin and adjusting the proportion of auxiliary materials, avoids the use of disintegrants such as sodium carboxymethyl starch and cross-linked polyvinylpyrrolidone, reduces the volume of amoxicillin capsules, reduces the content of high molecular impurities in amoxicillin capsules, and improves production efficiency. Summary of the invention

[0004] (I) Technical problems solved: In view of the deficiencies of the prior art, the present invention provides a method for preparing amoxicillin capsules. Dry granulation is used to control the particle size range of the raw materials. Without using a disintegrant, the solubility of the capsules is improved by adjusting the amount of magnesium stearate, so as to achieve the purpose of having a dissolution behavior similar to that of the original preparation. Under the premise of meeting the quality requirements of the drug, the present invention is simpler than the prior art, the volume of the capsules is reduced, and the compliance of clinical use is improved. By controlling the particle size of the amoxicillin raw material and the ratio to the auxiliary material magnesium stearate, the dissolution and stability of the amoxicillin capsules can be ensured to be good.

[0005] (II) Technical solution: A method for preparing amoxicillin capsules, comprising 250 parts of amoxicillin and 1.44 parts of magnesium stearate.

[0006] The preparation method of amoxicillin capsules is as follows: (1) Amoxicillin was added into a dry granulator and granulated through a 1.0 mm sieve to obtain amoxicillin granules. The amoxicillin granules were sucked into a rotary vibrating screen through a vacuum feeder, coarse particles were removed through a 20-mesh sieve, fine powder was removed through a 60-mesh sieve, and the fine powder was re-granulated to obtain amoxicillin granules and fine powder.

[0007] (2) Add amoxicillin granules and fine powder into a mixer, close the feed port, set the mixing time to 10 minutes, and mix at a constant speed to obtain amoxicillin granules; then add magnesium stearate into the mixer, close the feed port, set the mixing time to 10 minutes, and mix at a constant speed to obtain an intermediate product.

[0008] (3) Take the intermediate product to test the content and calculate the filling quantity based on the content.

[0009] (4) generating a production instruction according to the filling quantity, and controlling a fully automatic capsule filling machine to perform filling to obtain capsules.

[0010] (5) Polish the filled capsules with a capsule polishing machine to obtain amoxicillin capsules. Finally, aluminum-plastic packaging is performed at a temperature of 18-26°C and a humidity of 45-55%.

[0011] Preferably, (1) the roller pressure of the medium dry granulator is 7.0 MPa, the horizontal push speed is 25 rpm, the material feeding speed is 15 rpm, the roller speed is 12 rpm, the roller gap is about 1.5 mm, the first-level granulation screen is a 5.0 mm round hole screen, the second-level granulation screen is a 1.0 mm round hole screen, the first-level granulation speed is 30 rpm, and the second-level granulation speed is 60 rpm.

[0012] Preferably, the temperature during mixing in (2) is 18-26° C. and the humidity is 45-55%.

[0013] Preferably, the temperature during filling in (4) is 18-26° C. and the humidity is 45-55%.

[0014] Preferably, the filling speed of the fully automatic capsule filling machine in (4) is 4000-5000 capsules / minute.

[0015] Preferably, the temperature during polishing in (5) is 18-26° C. and the humidity is 45-55%.

[0016] Preferably, the weight of a single amoxicillin capsule in (5) is 0.25 g.

[0017] Preferably, the dissolution test method of amoxicillin capsules is as follows: 900 ml of water, pH 1.2 hydrochloric acid solution, pH 4.0 acetate buffer, and pH 6.8 phosphate buffer are used as dissolution media, respectively, at a speed of 100 revolutions per minute, sampling is performed at each set time point, an appropriate amount of solution is taken, filtered, an appropriate amount of the filtrate is accurately measured, and quantitatively diluted with the dissolution medium to prepare a solution containing approximately 130 μg of amoxicillin per 1 mL, and the absorbance is detected at a wavelength of 272 nm by a UV-visible spectrophotometer; another appropriate amount of amoxicillin reference substance is taken, dissolved in the dissolution medium and quantitatively diluted to prepare a solution containing approximately 130 μg per 1 ml, as a control solution, and measured in the same way to calculate the dissolution amount of each particle.

[0018] Preferably, the preparation method of the acetate buffer solution of pH 4.0 is as follows: 1.22 g of sodium acetate trihydrate is added with 20.5 mL of 2 mol / L acetic acid solution, diluted with water to 1000 ml, and shaken to obtain the acetate buffer solution.

[0019] Preferably, the preparation method of pH 6.8 phosphate buffer is: take 250 ml of 0.2 mol / L potassium dihydrogen phosphate solution, add 112 ml of 0.2 mol / L sodium hydroxide solution, dilute with water to 1000 mL, shake well, and obtain phosphate buffer.

[0020] (III) Technical Effect: The present invention uses dry granulation to control the particle size range of the raw materials. Without using a disintegrant, the dissolution rate of the capsule is improved by adjusting the amount of magnesium stearate, so as to achieve the purpose of similar dissolution behavior between the product and the original preparation. On the premise of meeting the quality requirements of the drug, the present invention is simpler than the existing technology, the volume of the capsule is reduced, and the compliance of clinical use is improved. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 is a summary of the dissolution results. DETAILED DESCRIPTION

[0022] In order to enable those skilled in the art to better understand the present application, the technical solutions in the embodiments of the present application are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in the field without creative work are within the scope of protection of the present application.

[0023] Embodiment 1: (1) Prepare raw materials and auxiliary materials. Take 250 parts by weight of amoxicillin as the raw material and 1.44 parts of magnesium stearate as the auxiliary material. It should be noted that the actual amount of amoxicillin added = amoxicillin (according to C 16 H 19N3O5S) prescription dosage / content / (1-water content), where the content and water content are tested according to the test method in the Amoxicillin Quality Standard of Part II of the Chinese Pharmacopoeia 2020 Edition.

[0024] (2) Granulation: The amoxicillin raw material is sucked into the dry granulator through the vacuum feeder, and the dry granulator is turned on. The parameters are set as follows: roller pressure 7.0 MPa, horizontal push speed 25 rpm, feeding speed 15 rpm, roller speed 12 rpm, roller gap about 1.5 mm, first-level granulation screen is 5.0 mm round hole screen, second-level granulation screen is 1.0 mm round hole screen, first-level granulation speed 30 rpm, second-level granulation speed 60 rpm, oscillating sieve mesh number upper layer 20 mesh, lower layer 60 mesh. The granulated amoxicillin granules are sucked into the oscillating sieve through the vacuum feeder for sieving, and the coarse particles larger than 20 mesh are discarded, and the particles between 20 mesh and 60 mesh are retained. The fine powder smaller than 60 mesh is re-granulated, and finally the amoxicillin granules and fine powder are obtained.

[0025] (3) Mixing: Add amoxicillin granules and fine powder into the mixer, close the feed port, and mix for 10 minutes. Then add magnesium stearate into the mixer, close the feed port, and mix for 10 minutes to obtain an intermediate product.

[0026] (4) Inspection of intermediate products: Take the intermediate products to test their content and calculate the filling quantity based on the content.

[0027] (5) Filling: After the amoxicillin content of the intermediate product is tested, the amount of mixed material required for 0.25 g of amoxicillin is calculated, the capsule filling machine speed is set to 4000 rpm, and the mixed material is accurately and quantitatively filled into No. 1 capsules using the capsule filling machine to obtain 0.25 g amoxicillin capsules.

[0028] (6) Polishing: Polish the filled amoxicillin capsules with a capsule polishing machine and place the capsules into a turnover container after polishing.

[0029] (7) Aluminum-plastic packaging: Use aluminum-plastic packaging and packaging.

[0030] Example 2 (1) Prepare raw materials and auxiliary materials. Take 250 parts by weight of amoxicillin as the raw material, 1.44 parts of magnesium stearate and 2.88 parts of silicon dioxide as the auxiliary materials. It should be noted that the actual amount of amoxicillin added = the amount of amoxicillin (calculated as C16H19N3O5S) prescribed / content / (1-water content), where the content and water content are tested according to the test method in the quality standard for amoxicillin in Part II of the 2020 edition of the Chinese Pharmacopoeia.

[0031] (2) Granulation: The amoxicillin raw material is sucked into the dry granulator through the vacuum feeder, and the dry granulator is turned on. The parameters are set as follows: roller pressure 7.0 MPa, horizontal push speed 25 rpm, feeding speed 15 rpm, roller speed 12 rpm, roller gap about 1.5 mm, first-level granulation screen is 5.0 mm round hole screen, second-level granulation screen is 1.0 mm round hole screen, first-level granulation speed 30 rpm, second-level granulation speed 60 rpm, oscillating sieve mesh number upper layer 20 mesh, lower layer 60 mesh. The granulated amoxicillin granules are sucked into the oscillating sieve through the vacuum feeder for sieving, and the coarse particles larger than 20 mesh are discarded, and the particles between 20 mesh and 60 mesh are retained. The fine powder smaller than 60 mesh is re-granulated, and finally the amoxicillin granules and fine powder are obtained.

[0032] (3) Mixing: Add amoxicillin granules and fine powder into the mixer, close the feed port, and mix for 10 minutes. Then add magnesium stearate into the mixer, close the feed port, and mix for 10 minutes to obtain an intermediate product.

[0033] (4) Inspection of intermediate products: Take the intermediate products to test their content and calculate the filling quantity based on the content.

[0034] (5) Filling: After the amoxicillin content of the intermediate product is tested, the amount of mixed material required for 0.25 g of amoxicillin is calculated, the capsule filling machine speed is set to 5000 rpm, and the mixed material is accurately and quantitatively filled into No. 1 capsules using the capsule filling machine to obtain 0.25 g amoxicillin capsules.

[0035] (6) Polishing: Polish the filled amoxicillin capsules with a capsule polishing machine and place the capsules into a turnover container after polishing.

[0036] (7) Aluminum-plastic packaging: Use aluminum-plastic packaging and packaging.

[0037] Example 3 (1) Prepare raw materials and auxiliary materials. Take 250 parts by weight of amoxicillin as raw material, 1.44 parts of magnesium stearate and 8.64 parts of cross-linked carboxymethyl cellulose sodium as auxiliary materials. It should be noted that the actual amount of amoxicillin added = amoxicillin (calculated as C16H19N3O5S) prescription dosage / content / (1-water content), where the content and water content are tested according to the test method in the quality standard for amoxicillin in Part II of the 2020 edition of the Chinese Pharmacopoeia.

[0038] (2) Granulation: The amoxicillin raw material is sucked into the dry granulator through the vacuum feeder, and the dry granulator is turned on. The parameters are set as follows: roller pressure 7.0 MPa, horizontal push speed 25 rpm, feeding speed 15 rpm, roller speed 12 rpm, roller gap about 1.5 mm, first-level granulation screen is 5.0 mm round hole screen, second-level granulation screen is 1.0 mm round hole screen, first-level granulation speed 30 rpm, second-level granulation speed 60 rpm, oscillating sieve mesh number upper layer 20 mesh, lower layer 60 mesh. The granulated amoxicillin granules are sucked into the oscillating sieve through the vacuum feeder for sieving, and the coarse particles larger than 20 mesh are discarded, and the particles between 20 mesh and 60 mesh are retained. The fine powder smaller than 60 mesh is re-granulated, and finally the amoxicillin granules and fine powder are obtained.

[0039] (3) Mixing: Add amoxicillin granules and fine powder into the mixer, close the feed port, and mix for 10 minutes. Then add magnesium stearate into the mixer, close the feed port, and mix for 10 minutes to obtain an intermediate product.

[0040] (4) Inspection of intermediate products: Take the intermediate products to test their content and calculate the filling quantity based on the content.

[0041] (5) Filling: After the amoxicillin content of the intermediate product is tested, the amount of mixed material required for 0.25 g of amoxicillin is calculated, the capsule filling machine speed is set to 4000 rpm, and the mixed material is accurately and quantitatively filled into No. 1 capsules using the capsule filling machine to obtain 0.25 g amoxicillin capsules.

[0042] (6) Polishing: Polish the filled amoxicillin capsules with a capsule polishing machine and place the capsules into a turnover container after polishing.

[0043] (7) Aluminum-plastic packaging: Use aluminum-plastic packaging and packaging.

[0044] Example 4 (1) Prepare raw materials and auxiliary materials. Take 250 parts by weight of amoxicillin as raw materials, 1.44 parts of magnesium stearate, 2.88 parts of silicon dioxide, and 8.64 parts of cross-linked sodium carboxymethyl cellulose as auxiliary materials. It should be noted that the actual amount of amoxicillin added = amoxicillin (calculated as C16H19N3O5S) prescription dosage / content / (1-water content), where the content and water content are tested according to the test method in the quality standard for amoxicillin in Part II of the 2020 edition of the Chinese Pharmacopoeia.

[0045] (2) Granulation: The amoxicillin raw material is sucked into the dry granulator through the vacuum feeder, and the dry granulator is turned on. The parameters are set as follows: roller pressure 7.0 MPa, horizontal push speed 25 rpm, feeding speed 15 rpm, roller speed 12 rpm, roller gap about 1.5 mm, first-level granulation screen is 5.0 mm round hole screen, second-level granulation screen is 1.0 mm round hole screen, first-level granulation speed 30 rpm, second-level granulation speed 60 rpm, oscillating sieve mesh number upper layer 20 mesh, lower layer 60 mesh. The granulated amoxicillin granules are sucked into the oscillating sieve through the vacuum feeder for sieving, and the coarse particles larger than 20 mesh are discarded, and the particles between 20 mesh and 60 mesh are retained. The fine powder smaller than 60 mesh is re-granulated, and finally the amoxicillin granules and fine powder are obtained.

[0046] (3) Mixing: Add amoxicillin granules and fine powder into the mixer, close the feed port, and mix for 10 minutes. Then add magnesium stearate into the mixer, close the feed port, and mix for 10 minutes to obtain an intermediate product.

[0047] (4) Inspection of intermediate products: Take the intermediate products to test their content and calculate the filling quantity based on the content.

[0048] (5) Filling: After the amoxicillin content of the intermediate product is tested, the amount of mixed material required for 0.25 g of amoxicillin is calculated, the capsule filling machine speed is set to 4000 rpm, and the mixed material is accurately and quantitatively filled into No. 1 capsules using the capsule filling machine to obtain 0.25 g amoxicillin capsules.

[0049] (6) Polishing: Polish the filled amoxicillin capsules with a capsule polishing machine and place the capsules into a turnover container after polishing.

[0050] (7) Aluminum-plastic packaging: Use aluminum-plastic packaging and packaging.

[0051] Example 5 (1) Prepare raw materials and auxiliary materials. Take 250 parts by weight of amoxicillin as the raw material and 2.16 parts of magnesium stearate as the auxiliary material. It should be noted that the actual amount of amoxicillin added = the prescribed amount of amoxicillin (calculated as C16H19N3O5S) / content / (1-water content), where the content and water content are tested according to the test method in the quality standard for amoxicillin in Part II of the 2020 edition of the Chinese Pharmacopoeia.

[0052] (2) Granulation: The amoxicillin raw material is sucked into the dry granulator through the vacuum feeder, and the dry granulator is turned on. The parameters are set as follows: roller pressure 7.0 MPa, horizontal push speed 25 rpm, feeding speed 15 rpm, roller speed 12 rpm, roller gap about 1.5 mm, first-level granulation screen is 5.0 mm round hole screen, second-level granulation screen is 1.0 mm round hole screen, first-level granulation speed 30 rpm, second-level granulation speed 60 rpm, oscillating sieve mesh number upper layer 20 mesh, lower layer 60 mesh. The granulated amoxicillin granules are sucked into the oscillating sieve through the vacuum feeder for sieving, and the coarse particles larger than 20 mesh are discarded, and the particles between 20 mesh and 60 mesh are retained. The fine powder smaller than 60 mesh is re-granulated, and finally the amoxicillin granules and fine powder are obtained.

[0053] (3) Mixing: Add amoxicillin granules and fine powder into the mixer, close the feed port, and mix for 10 minutes. Then add magnesium stearate into the mixer, close the feed port, and mix for 10 minutes to obtain an intermediate product.

[0054] (4) Inspection of intermediate products: Take the intermediate products to test their content and calculate the filling quantity based on the content.

[0055] (5) Filling: After the amoxicillin content of the intermediate product is tested, the amount of mixed material required for 0.25 g of amoxicillin is calculated, the capsule filling machine speed is set to 4000 rpm, and the mixed material is accurately and quantitatively filled into No. 1 capsules using the capsule filling machine to obtain 0.25 g amoxicillin capsules.

[0056] (6) Polishing: Polish the filled amoxicillin capsules with a capsule polishing machine and place the capsules into a turnover container after polishing.

[0057] (7) Aluminum-plastic packaging: Use aluminum-plastic packaging and packaging.

[0058] Example 6 (1) A. Prepare raw materials and auxiliary materials. Take 250 parts by weight of amoxicillin as the raw material and 2.88 parts of magnesium stearate as the auxiliary material. It should be noted that the actual amount of amoxicillin added = the prescribed amount of amoxicillin (calculated as C16H19N3O5S) / content / (1-water content), where the content and water content are tested according to the test method in the quality standard for amoxicillin in Part II of the 2020 edition of the Chinese Pharmacopoeia.

[0059] (2) Granulation: The amoxicillin raw material is sucked into the dry granulator through the vacuum feeder, and the dry granulator is turned on. The parameters are set as follows: roller pressure 7.0 MPa, horizontal push speed 25 rpm, feeding speed 15 rpm, roller speed 12 rpm, roller gap about 1.5 mm, first-level granulation screen is 5.0 mm round hole screen, second-level granulation screen is 1.0 mm round hole screen, first-level granulation speed 30 rpm, second-level granulation speed 60 rpm, oscillating sieve mesh number upper layer 20 mesh, lower layer 60 mesh. The granulated amoxicillin granules are sucked into the oscillating sieve through the vacuum feeder for sieving, and the coarse particles larger than 20 mesh are discarded, and the particles between 20 mesh and 60 mesh are retained. The fine powder smaller than 60 mesh is re-granulated, and finally the amoxicillin granules and fine powder are obtained.

[0060] (3) Mixing: Add amoxicillin granules and fine powder into the mixer, close the feed port, and mix for 10 minutes. Then add magnesium stearate into the mixer, close the feed port, and mix for 10 minutes to obtain an intermediate product.

[0061] (4) Inspection of intermediate products: Take the intermediate products to test their content and calculate the filling quantity based on the content.

[0062] (5) Filling: After testing the amoxicillin content in the intermediate product, calculate the amount of mixed material required for 0.25 g of amoxicillin, set the capsule filling machine speed to 4000-5000 rpm, and use the capsule filling machine to accurately and quantitatively fill the mixed material into No. 1 capsules to obtain 0.25 g amoxicillin capsules.

[0063] (6) Polishing: Polish the filled amoxicillin capsules with a capsule polishing machine and place the capsules into a turnover container after polishing.

[0064] (7) Aluminum-plastic packaging: Use aluminum-plastic packaging and packaging.

[0065] Dissolution test method: Take the amoxicillin capsule samples prepared in Examples 1-6, use 900 ml of water, pH 1.2 hydrochloric acid solution, pH 4.0 acetate buffer, and pH 6.8 phosphate buffer as dissolution media, respectively, at a speed of 100 revolutions per minute, operate according to the law, take samples at the respective set time points, take an appropriate amount of solution, filter, accurately measure an appropriate amount of the filtrate, and quantitatively dilute it with the dissolution medium to prepare a solution containing about amoxicillin per 1 ml (according to C 16 H 19 N3O5S) solution of 130µg, and detect the absorbance at a wavelength of 272nm by UV-visible spectrophotometer; take an appropriate amount of amoxicillin reference substance, add dissolution medium to dissolve and quantitatively dilute to make a solution containing about 130µg per 1ml, as the reference solution, and measure in the same way to calculate the dissolution amount of each tablet.

[0066] For comparative example 1, the generic reference preparation was purchased from a licensed dealer, Beecham Group Plc (affiliated with GSK), with batch numbers 2383 and 2368.

[0067] Dissolution medium preparation: pH 1.2 hydrochloric acid solution, take 7.65ml hydrochloric acid, dilute to 1000ml with water, shake well, and you have it. pH 4.0 acetate buffer, take 1.22g sodium acetate trihydrate, add 20.5ml 2mol / L acetic acid solution, dilute to 1000ml with water, shake well, and you have it. 2mol / L acetic acid solution, take 120g (114ml) glacial acetic acid and dilute to 1000ml with water, and you have it.

[0068] pH 6.8 phosphate buffer solution: take 250ml of 0.2mol / L potassium dihydrogen phosphate solution, add 112ml of 0.2mol / L sodium hydroxide solution, dilute to 1000ml with water, shake well, and you have it. 0.2mol / L potassium dihydrogen phosphate solution: take 27.22g of potassium dihydrogen phosphate and dilute to 1000ml with water. 0.2mol / L sodium hydroxide solution: take 8.00g of sodium hydroxide and dilute to 1000ml with water.

[0069] Table 1 Sampling time and limit requirements Sampling operation: 10 ml of sample (replenishment 10 ml) was taken at the above time points, filtered through a 0.45 µm (25 mm diameter) polyethersulfone filter membrane, 3 ml of the initial filtrate was removed, and the absorbance of the subsequent filtrate was detected at a wavelength of 272 nm.

[0070] Results: For the comparison group, the reference preparation was tested for dissolution as a comparison reference. Figure 1 It can be seen that the first group: amoxicillin capsules prepared according to the preparation method of amoxicillin capsules in Example 1 were subjected to dissolution test, and the test results were compared with the dissolution of amoxicillin capsules in the control group. The dissolution behaviors of the amoxicillin capsules in this group in the four media were similar.

[0071] The second group: amoxicillin capsules prepared according to the preparation method of amoxicillin capsules in Example 2 were subjected to dissolution test, and the test results were compared with the dissolution of amoxicillin capsules in the control group. The dissolution behaviors of amoxicillin capsules in this group in the four media were similar.

[0072] The third group: amoxicillin capsules prepared according to the preparation method of amoxicillin capsules in Example 3 were subjected to dissolution test. The test results were compared with the dissolution of amoxicillin capsules in the control group. The dissolution behavior of amoxicillin capsules in this group in the four media was faster.

[0073] The fourth group: amoxicillin capsules prepared according to the preparation method of amoxicillin capsules in Example 4 were subjected to dissolution test. The test results were compared with the dissolution of amoxicillin capsules in the control group. The dissolution behavior of amoxicillin capsules in this group in the four media was faster.

[0074] The fifth group: amoxicillin capsules prepared according to the preparation method of amoxicillin capsules in Example 5 were subjected to dissolution test. The test results were compared with the dissolution of amoxicillin capsules in the control group. The dissolution behaviors of amoxicillin capsules in this group in the four media were similar.

[0075] Group 6: Amoxicillin capsules prepared according to the preparation method of amoxicillin capsules in Example 6 were subjected to dissolution test, and the test results were compared with the dissolution of amoxicillin capsules in the control group. The dissolution behaviors of amoxicillin capsules in this group in aqueous medium, pH 1.2 hydrochloric acid solution, and pH 6.8 phosphate buffer were similar, but the pH 4.0 medium encapsulation resulted in a large RSD.

[0076] The product prepared with the first group of raw materials and excipients has good dissolution behavior and is similar to that of the original product.

[0077] The products prepared with the second, third and fourth groups of raw materials and excipients have worse dissolution behaviors as the more types of excipients there are, which is quite different from the dissolution behaviors of the original products.

[0078] The products prepared with the fifth and sixth groups of raw materials and excipients have worse dissolution behavior as the amount of excipients increases, which is quite different from the dissolution behavior of the original product.

[0079] Therefore, the amoxicillin preparation method provided in the present application can improve the solubility of amoxicillin capsules, prepare amoxicillin capsules with high solubility, and solve the problem of low solubility of existing amoxicillin capsules.

[0080] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, several improvements, modifications, and equivalent substitutions may be made without departing from the principles of the present invention, and all of them should be included in the protection scope of the present invention.

Claims

1. A method for preparing amoxicillin capsules, characterized in that: The amoxicillin capsule comprises, by weight, 250 parts of amoxicillin; 1.44 parts of magnesium stearate; The preparation method of the amoxicillin capsule is: (1) adding amoxicillin to a dry granulator and granulating through a 1.0 mm sieve to obtain amoxicillin granules, sucking the amoxicillin granules into a rotary vibrating sieve through a vacuum feeder, removing coarse particles through a 20-mesh sieve, removing fine powder through a 60-mesh sieve, and re-granulating the fine powder to obtain amoxicillin granules and fine powder; (2) adding amoxicillin granules and fine powder into a mixer, closing the feed port, setting the mixing time to 10 minutes, and mixing at a constant speed to obtain amoxicillin granules; then adding magnesium stearate into the mixer, closing the feed port, setting the mixing time to 10 minutes, and mixing at a constant speed to obtain an intermediate product; (3) Take the intermediate product to test the content and calculate the filling quantity based on the content; (4) generating a production instruction according to the filling quantity, and controlling a fully automatic capsule filling machine to perform filling to obtain capsules; (5) Polishing the filled capsules with a capsule polishing machine to obtain amoxicillin capsules.

2. The method for preparing amoxicillin capsules according to claim 1, characterized in that: The dry granulator in (1) has a roller pressure of 7.0 MPa, a horizontal push speed of 25 rpm, a material feeding speed of 15 rpm, a roller speed of 12 rpm, a roller gap of about 1.5 mm, a first-level granulation screen with a 5.0 mm round hole screen, a second-level granulation screen with a 1.0 mm round hole screen, a first-level granulation speed of 30 rpm, and a second-level granulation speed of 60 rpm.

3. The method for preparing amoxicillin capsules according to claim 1, characterized in that: The temperature during mixing in (2) is 18-26° C. and the humidity is 45-55%.

4. The method for preparing amoxicillin capsules according to claim 1, characterized in that: The temperature during filling in (4) is 18-26° C. and the humidity is 45-55%.

5. The method for preparing amoxicillin capsules according to claim 1, characterized in that: The filling speed of the fully automatic capsule filling machine in (4) is 4000-5000 capsules / minute.

6. The method for preparing amoxicillin capsules according to claim 1, characterized in that: The temperature during polishing in (5) is 18-26° C. and the humidity is 45-55%.

7. The method for preparing amoxicillin capsules according to claim 1, characterized in that: The weight of a single amoxicillin capsule in (5) is 0.25 g.

8. A method for detecting the dissolution of amoxicillin capsules obtained by the preparation method according to claims 1-7, characterized in that: The detection method comprises the following steps: using 900 ml of water, pH 1.2 hydrochloric acid solution, pH 4.0 acetate buffer solution, and pH 6.8 phosphate buffer solution as dissolution media, respectively, at a rotation speed of 100 revolutions per minute, sampling at respective set time points, taking an appropriate amount of solution, filtering, accurately measuring an appropriate amount of subsequent filtrate, quantitatively diluting with the dissolution medium to prepare a solution containing approximately 130 μg of amoxicillin per 1 ml, and detecting the absorbance at a wavelength of 272 nm using an ultraviolet-visible spectrophotometer; taking an appropriate amount of amoxicillin reference substance, adding the dissolution medium to dissolve and quantitatively diluting to prepare a solution containing approximately 130 μg per 1 ml, as a reference solution, measuring in the same manner, and calculating the dissolution amount of each particle.

9. The dissolution detection method of amoxicillin capsules according to claim 8, characterized in that: The preparation method of the acetate buffer solution of pH 4.0 is as follows: 1.22 g of sodium acetate trihydrate is added with 20.5 mL of 2 mol / L acetic acid solution, and the mixture is diluted to 1000 ml with water, and shaken to obtain the acetate buffer solution.

10. The method for detecting the dissolution rate of amoxicillin capsules according to claim 8, characterized in that: The preparation method of the pH 6.8 phosphate buffer is as follows: take 250 ml of 0.2 mol / L potassium dihydrogen phosphate solution, add 112 ml of 0.2 mol / L sodium hydroxide solution, dilute with water to 1000 mL, shake well, and obtain the phosphate buffer.

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