Cefadroxil capsule as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of medicines, and particularly relates to a cefadroxil capsule as well as a preparation method and application thereof. The cefadroxil capsule comprises quick-release particles, slow-release particles and a lubricant, the slow-release particles comprise cefadroxil, hydroxypropyl cellulose, hydroxypropyl methylcellulose, a filler and an adhesive, and the weight ratio of the hydroxypropyl cellulose to the hydroxypropyl methylcellulose is 1: (2-10). The cefadroxil capsule contains the quick-release particles and the slow-release particles, and the quick-release particles can quickly reach an effective steady-state blood concentration, so that the medicine has an antibacterial effect as soon as possible, and the generation of drug resistance is prevented; the sustained-release granules can avoid the'peak valley 'phenomenon caused by frequent administration of a common preparation, reduce the administration frequency and greatly facilitate patients.

Description

Technical Field

[0001] The invention belongs to the technical field of medicines, and in particular relates to a cefoperazone capsule and a preparation method and application thereof. Background Art

[0002] Sustained-release preparations are preparations that require at least one less dose per day or have a longer dosing interval than corresponding ordinary immediate-release preparations. They can enable the human body to maintain therapeutic blood drug concentrations for a longer period of time, instead of the rapid decline seen with ordinary preparations. This avoids the "peak and valley" phenomenon that occurs with frequent dosing of ordinary preparations, improves the safety, effectiveness or compliance of the drug, and thus reduces the frequency of medication, greatly facilitating patients, especially those who take long-term medications.

[0003] Chinese invention patent publication number CN110709068A discloses an improved sustained-release high-load pharmaceutical composition, which provides increased stability, higher drug loading and suitable drug dissolution characteristics. The composition includes: (a) a drug component, which contains a therapeutically effective amount of a drug; (b) a sustained-release component containing a cross-linked polyacrylic acid polymer, which is a carbomer homopolymer, a carbomer copolymer, a carbomer interpolymer, a polycarbophil or a mixture thereof; and (c) a buffer component, which contains a magnesium-containing buffer; wherein the drug component accounts for at least 50% of the weight of the composition.

[0004] Another Chinese invention patent publication number CN103599088A discloses a cephalexin bioadhesive sustained-release capsule and a preparation method thereof, which is obtained by filling one cephalexin immediate-release tablet and five cephalexin bioadhesive sustained-release tablets into the same hard capsule, containing a total of 250 mg of cephalexin active ingredient. The novel oral preparation has a variable release characteristic, which can achieve the characteristics of cephalexin from immediate release to delayed release, and obtain a stable blood drug concentration.

[0005] Cefadroxil is a semi-synthetic first-generation oral cephalosporin. It is a bactericidal broad-spectrum cephalosporin antibiotic with good antibacterial effects on Staphylococcus, Streptococcus, Escherichia coli, etc. It is mainly used to treat urinary tract infections, skin and soft tissue infections, pharyngitis, tonsillitis and other diseases caused by sensitive bacteria. Cefadroxil is rapidly absorbed after oral administration, and its blood elimination half-life is t 1 / 2 1.27-1.5h, food has an effect on the peak plasma concentration and t 1 / 2 There was no significant effect.

[0006] The current marketed dosage forms of cefadroxil are mainly tablets, capsules, granules and dry suspensions, etc., and there is no sustained-release preparation. Therefore, providing a cefadroxil preparation that can achieve a sustained-release effect and has a simple preparation method has important application value. Summary of the invention

[0007] In view of the problems existing in the prior art, the present invention provides a cefoperazone capsule and a preparation method and application thereof.

[0008] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0009] A cefoperazone capsule comprises quick-release granules, sustained-release granules and a lubricant. The sustained-release granules comprise cefoperazone, hydroxypropyl cellulose, hypromellose, a filler and a binder. The weight ratio of the hydroxypropyl cellulose to the hypromellose is 1:2-10.

[0010] Preferably, the weight ratio of hydroxypropyl cellulose to hydroxypropyl methyl cellulose is 1:2.6-9.

[0011] Preferably, the type of hydroxypropyl cellulose is HXF or EXF.

[0012] Preferably, the hydroxypropoxy content of the hypromellose is 4-12%, and the average molecular weight of the hypromellose is 75000-140000.

[0013] More preferably, the model of the hypromellose is K100M or K100LV.

[0014] Preferably, the filler is selected from one or more of microcrystalline cellulose, starch and mannitol.

[0015] More preferably, the filler is microcrystalline cellulose or pregelatinized starch.

[0016] Preferably, the binder is selected from one or more of povidone, copovidone and ethyl cellulose.

[0017] More preferably, the binder is povidone K30.

[0018] Preferably, the immediate-release granules comprise cefadroxil and a disintegrant.

[0019] Preferably, the disintegrant is selected from one or more of sodium carboxymethyl starch, cross-linked sodium carboxymethyl cellulose and cross-linked polyvinylpyrrolidone.

[0020] More preferably, the disintegrant is croscarmellose sodium.

[0021] Preferably, the lubricant is selected from one or more of magnesium stearate, talc and colloidal silicon dioxide.

[0022] More preferably, the lubricant is magnesium stearate.

[0023] Preferably, the cefoperazone capsule comprises the following components in parts by mass:

[0024] Immediate-release granules: 120-130 parts of cefadroxil and 0-5 parts of disintegrant;

[0025] Sustained-release granules: 360-390 parts of cefadroxil, 20-50 parts of hydroxypropyl cellulose, 130-180 parts of hypromellose, 20-60 parts of filler and 1-10 parts of binder;

[0026] Lubricant: 1-5 parts.

[0027] More preferably, the cefoperazone capsule comprises the following components in parts by mass:

[0028] Immediate-release granules: 125-130 parts of cefadroxil and 0-3 parts of disintegrant;

[0029] Sustained-release granules: 370-380 parts of cefadroxil, 20-50 parts of hydroxypropyl cellulose, 120-180 parts of hypromellose, 20-60 parts of filler and 5-10 parts of binder;

[0030] Lubricant: 2-3 parts.

[0031] Preferably, the cefoperazone capsule further comprises a pharmaceutically acceptable excipient.

[0032] The present invention also provides a method for preparing the above-mentioned cefoperazone capsule, comprising the following steps:

[0033] (1) firstly mix cefadroxil, hydroxypropyl cellulose, hypromellose and a filler, and then add a binder to obtain sustained-release granules;

[0034] (2) mixing cefadroxil with a disintegrant to obtain immediate-release granules;

[0035] (3) Mix the sustained-release granules and the immediate-release granules, add a lubricant, and fill the capsules to obtain the product.

[0036] Preferably, after the addition of the binder in step (1), the mixture needs to be sieved through a 30-50 mesh sieve, and after the mixing in step (3), the mixture needs to be sieved through a 20-40 mesh sieve.

[0037] The present invention also provides the use of the cefadroxil capsule or the cefadroxil capsule prepared by the preparation method in the preparation of antibiotic drugs.

[0038] Compared with the prior art, the present invention has the following beneficial effects:

[0039] (1) The cefoperazone capsules of the present invention comprise quick-release granules and sustained-release granules. The quick-release granules can rapidly reach an effective steady-state blood drug concentration, allowing the drug to produce an antibacterial effect as quickly as possible and preventing the development of drug resistance; the sustained-release granules can avoid the "peak and valley" phenomenon caused by frequent administration of common preparations and reduce the number of medications, greatly facilitating patients.

[0040] (2) The present invention utilizes the synergistic effect of hydroxypropyl cellulose and hydroxypropyl methylcellulose in the sustained-release granules to make the sustained-release rate more reasonable. The drug dissolution rate reaches 20-35% in the first hour, 50-75% in the fourth hour, and is basically completely dissolved in the tenth hour. While effectively prolonging the drug release, it also takes effect in a timely manner, is more conducive to human absorption, and improves the bioavailability of the drug. DETAILED DESCRIPTION

[0041] It is worth noting that the raw materials used in the present invention are all common commercially available products, among which the model of magnesium stearate is SH-YM-M.

[0042] Example 1

[0043] A cefoperazone capsule, the prescription composition of which is shown in Table 1.

[0044] Table 1 Prescription composition

[0045]

[0046] The preparation method of the above-mentioned cefadroxil capsule is as follows:

[0047] (1) Preparation of sustained-release granules: Cefuroxil, microcrystalline cellulose 101, hypromellose K100M and hydroxypropyl cellulose HXF were mixed according to the prescription ratio in Table 1, and the mixture was made into a soft material with povidone K30 solution. After passing through a 40-mesh sieve, the mixture was dried to obtain sustained-release granules.

[0048] (2) Preparation of immediate-release granules: Cefuroxil and croscarmellose sodium were mixed according to the prescription ratio in Table 1 to obtain immediate-release granules.

[0049] (3) Preparation of cefadroxil capsules: After mixing the sustained-release granules and the immediate-release granules, the granules were sieved through a 30-mesh sieve, and the prescribed amount of magnesium stearate was added and mixed evenly. Finally, the mixture was filled into empty gelatin capsules to obtain cefadroxil capsules.

[0050] Example 2

[0051] A cefoperazone capsule, the prescription composition of which is shown in Table 2.

[0052] Table 2 Prescription composition

[0053]

[0054] The preparation method of the above-mentioned cefadroxil capsule is as follows:

[0055] (1) Preparation of sustained-release granules: Cefuroxil, microcrystalline cellulose 101, hypromellose K100M and hydroxypropyl cellulose HXF were mixed according to the prescription ratio in Table 2, and the mixture was made into a soft material with povidone K30 solution. After passing through a 40-mesh sieve, the mixture was dried to obtain sustained-release granules.

[0056] (2) Preparation of immediate-release granules: Cefuroxil and croscarmellose sodium were mixed according to the prescription ratio in Table 2 to obtain immediate-release granules.

[0057] (3) Preparation of cefadroxil capsules: After mixing the sustained-release granules and the immediate-release granules, the granules were sieved through a 30-mesh sieve, and the prescribed amount of magnesium stearate was added and mixed evenly. Finally, the mixture was filled into empty gelatin capsules to obtain cefadroxil capsules.

[0058] Example 3

[0059] A cefoperazone capsule, the prescription composition of which is shown in Table 3.

[0060] Table 3 Prescription composition

[0061]

[0062] The preparation method of the above-mentioned cefadroxil capsule is as follows:

[0063] (1) Preparation of sustained-release granules: Cefuroxil, microcrystalline cellulose 101, hypromellose K100M and hydroxypropyl cellulose HXF were mixed according to the prescription ratio in Table 3, and the mixture was made into a soft material with povidone K30 solution. After passing through a 40-mesh sieve, the mixture was dried to obtain sustained-release granules.

[0064] (2) Preparation of immediate-release granules: Cefuroxil and croscarmellose sodium were mixed according to the prescription ratio in Table 3 to obtain immediate-release granules.

[0065] (3) Preparation of cefadroxil capsules: After mixing the sustained-release granules and the immediate-release granules, the granules were sieved through a 30-mesh sieve, and the prescribed amount of magnesium stearate was added and mixed evenly. Finally, the mixture was filled into empty gelatin capsules to obtain cefadroxil capsules.

[0066] Example 4

[0067] A cefoperazone capsule, the prescription composition of which is shown in Table 4.

[0068] Table 4 Prescription composition

[0069]

[0070]

[0071] The preparation method of the above-mentioned cefadroxil capsule is as follows:

[0072] (1) Preparation of sustained-release granules: Cefuroxil, microcrystalline cellulose 101, hypromellose K100M and hydroxypropyl cellulose HXF were mixed according to the prescription ratio in Table 4, and the mixture was made into a soft material with povidone K30 solution. After passing through a 40-mesh sieve, the mixture was dried to obtain sustained-release granules.

[0073] (2) Preparation of Cefadroxil Capsules: After mixing the sustained-release granules and the immediate-release granules of Cefadroxil, the granules are sieved through a 30-mesh sieve, and the prescribed amount of magnesium stearate is added and mixed evenly. Finally, the mixture is filled into empty gelatin capsules to obtain Cefadroxil Capsules.

[0074] Example 5

[0075] A cefoperazone capsule, the prescription composition of which is shown in Table 5.

[0076] Table 5 Prescription composition

[0077]

[0078] The preparation method of the above-mentioned cefadroxil capsule is as follows:

[0079] (1) Preparation of sustained-release granules: Cefuroxil, pregelatinized starch, hydroxypropyl methylcellulose K200M and hydroxypropyl cellulose EXF were mixed according to the prescription ratio in Table 5, and the mixture was made into a soft material with povidone K30 solution. After passing through a 40-mesh sieve, the mixture was dried to obtain sustained-release granules.

[0080] (2) Preparation of Cefadroxil Capsules: After mixing the sustained-release granules and the immediate-release granules of Cefadroxil, the granules were sieved through a 30-mesh sieve, and the prescribed amount of talcum powder was added and mixed evenly. Finally, the mixture was filled into gelatin hollow capsules to obtain Cefadroxil Capsules.

[0081] Comparative Example 1

[0082] The commercially available cefadroxil capsules were developed by TEVA PHARMACEUTICALS.

[0083] Comparative Example 2

[0084] Compared with Example 1, the only difference is that the prescription does not contain hydroxypropylcellulose HXF.

[0085] A cefoperazone capsule, the prescription composition of which is shown in Table 6.

[0086] Table 6 Prescription composition

[0087]

[0088] The preparation method of the above-mentioned cefadroxil capsule is as follows:

[0089] (1) Preparation of sustained-release granules: Cefuroxil, microcrystalline cellulose 101 and hypromellose K100M were mixed according to the prescription ratio in Table 6, and the mixture was made into a soft material with povidone K30 solution. After passing through a 40-mesh sieve, the mixture was dried to obtain sustained-release granules.

[0090] (2) Preparation of immediate-release granules: Cefuroxil and croscarmellose sodium were mixed according to the prescription ratio in Table 6 to obtain immediate-release granules.

[0091] (3) Preparation of cefadroxil capsules: After mixing the sustained-release granules and the immediate-release granules, the granules were sieved through a 30-mesh sieve, and the prescribed amount of magnesium stearate was added and mixed evenly. Finally, the mixture was filled into empty gelatin capsules to obtain cefadroxil capsules.

[0092] Comparative Example 3

[0093] Compared with Example 1, the only difference is that the prescription does not contain hypromellose K100M.

[0094] A cefoperazone capsule, the prescription composition of which is shown in Table 7.

[0095] Table 7 Prescription composition

[0096]

[0097]

[0098] The preparation method of the above-mentioned cefadroxil capsule is as follows:

[0099] (1) Preparation of sustained-release granules: Cefuroxil, microcrystalline cellulose 101 and hydroxypropyl cellulose HXF were mixed according to the prescription ratio in Table 7, and the mixture was made into a soft material with povidone K30 solution. After passing through a 40-mesh sieve, the mixture was dried to obtain sustained-release granules.

[0100] (2) Preparation of immediate-release granules: Cefuroxil and croscarmellose sodium were mixed according to the prescription ratio in Table 7 to obtain immediate-release granules.

[0101] (3) Preparation of cefadroxil capsules: After mixing the sustained-release granules and the immediate-release granules, the granules were sieved through a 30-mesh sieve, and the prescribed amount of magnesium stearate was added and mixed evenly. Finally, the mixture was filled into empty gelatin capsules to obtain cefadroxil capsules.

[0102] Comparative Example 4

[0103] Compared with Example 1, the only difference is that the hypromellose K100M in the prescription is replaced by polyoxyethylene 301.

[0104] A cefoperazone capsule, the prescription composition of which is shown in Table 8.

[0105] Table 8 Prescription composition

[0106]

[0107] The preparation method of the above-mentioned cefadroxil capsule is as follows:

[0108] (1) Preparation of sustained-release granules: Cefuroxil, microcrystalline cellulose 101, polyoxyethylene 301 and hydroxypropyl cellulose HXF were mixed according to the prescription ratio in Table 8, and the mixture was made into a soft material with povidone K30 solution. After passing through a 40-mesh sieve, the mixture was dried to obtain sustained-release granules.

[0109] (2) Preparation of immediate-release granules: Cefuroxil and croscarmellose sodium were mixed according to the prescription ratio in Table 8 to obtain immediate-release granules.

[0110] (3) Preparation of cefadroxil capsules: After mixing the sustained-release granules and the immediate-release granules, the granules were sieved through a 30-mesh sieve, and the prescribed amount of magnesium stearate was added and mixed evenly. Finally, the mixture was filled into empty gelatin capsules to obtain cefadroxil capsules.

[0111] Comparative Example 5

[0112] Compared with Example 1, the only difference is that the hypromellose K100M in the prescription is replaced by ethylcellulose N100.

[0113] A cefoperazone capsule, the prescription composition of which is shown in Table 9.

[0114] Table 9 Prescription composition

[0115]

[0116] The preparation method of the above-mentioned cefadroxil capsule is as follows:

[0117] (1) Preparation of sustained-release granules: Cefuroxil, microcrystalline cellulose 101, ethyl cellulose N100 and hydroxypropyl cellulose HXF were mixed according to the prescription ratio in Table 9, and the mixture was made into a soft material with povidone K30 solution. After passing through a 40-mesh sieve, the mixture was dried to obtain sustained-release granules.

[0118] (2) Preparation of immediate-release granules: Cefuroxil and croscarmellose sodium were mixed according to the prescription ratio in Table 9 to obtain immediate-release granules.

[0119] (3) Preparation of cefadroxil capsules: After mixing the sustained-release granules and the immediate-release granules, the granules were sieved through a 30-mesh sieve, and the prescribed amount of magnesium stearate was added and mixed evenly. Finally, the mixture was filled into empty gelatin capsules to obtain cefadroxil capsules.

[0120] Comparative Example 6

[0121] Compared with Example 1, the only difference is that the ratio of hydroxypropylcellulose HXF and hydroxypropylmethylcellulose K100M is different.

[0122] A cefoperazone capsule, the prescription composition of which is shown in Table 10.

[0123] Table 10 Prescription composition

[0124]

[0125]

[0126] The preparation method of the above-mentioned cefadroxil capsules is the same as that in Example 1.

[0127] Comparative Example 7

[0128] Compared with Example 1, the only difference is the preparation process.

[0129] A cefoperazone capsule, the prescription composition of which is shown in Table 11.

[0130] Table 11 Prescription composition

[0131] prescription Dosage (mg / tablet) Proportion Cefadroxil 500 68.49％ Croscarmellose Sodium 3 0.41％ Microcrystalline Cellulose 101 50 6.85％ Hydroxypropyl methylcellulose K100M 150 20.55％ Hydroxypropylcellulose HXF 20 2.74％ Povidone K30 5 0.69％ Magnesium Stearate 2 0.27％ total 730 100.00％

[0132] The preparation method of the above-mentioned cefadroxil capsules is as follows: the raw and auxiliary materials in the prescription amounts of the above-mentioned Table 11 are evenly mixed and then directly filled into capsules to obtain cefadroxil capsules.

[0133] Test Case

[0134] The dissolution experiments were carried out on the cefoperazone capsules of Examples 1-5 and Comparative Examples 1-7, referring to the second method of 0931 of the fourth general rules of the Chinese Pharmacopoeia 2020 edition.

[0135] Dissolution conditions: 900 mL of water is used as the dissolution medium, the speed is 100 revolutions per minute, the medium temperature is 37 ± 0.5 ° C, operate according to the law, take samples after 30 minutes, filter, and take the filtrate as the test solution. Take an appropriate amount of cefadroxil reference substance (source: China National Institute for Inspection), accurately weigh it, and use the medium to prepare a reference substance solution of corresponding concentration. Use HPLC method to inject the reference substance solution and the test solution respectively, record the chromatogram, and calculate the dissolution of each tablet, with a limit of 80% of the labeled amount.

[0136] Table 12 Dissolution data

[0137] serial number Dissolution in the first hour (%) Dissolution at 4 hours (%) Dissolution at 10 hours (%) Example 1 27 66 101 Example 2 25 56 94 Example 3 28 60 100 Example 4 25 63 97 Example 5 30 55 98 Comparative Example 1 101 / / Comparative Example 2 26 49 99 Comparative Example 3 42 88 99 Comparative Example 4 56 95 102 Comparative Example 5 25 43 76 Comparative Example 6 30 73 99 Comparative Example 7 46 85 99

[0138] The dissolution test results are shown in Table 12. According to the dissolution data in Table 12, it can be seen that:

[0139] The dissolution rate of the cefadroxil capsules prepared in Examples 1-5 is slow, with a dissolution rate of 55-70% in the 4th hour and substantially complete dissolution in the 10th hour, which effectively prolongs the drug release while achieving timely onset of action, is more conducive to human absorption, and improves bioavailability.

[0140] Compared with Example 1, the sustained-release effect of the cefadroxil capsules prepared in Comparative Example 2 is stronger, and the dissolution rate at the 4th hour is less than 55%, while the cefadroxil capsules prepared in Comparative Example 3 have a certain sustained-release effect, but the dissolution rate at the 4th hour has reached more than 85%, and the sustained-release effect is not significant enough, indicating that the hydroxypropyl cellulose and hydroxypropyl methylcellulose in the sustained-release granules have a synergistic effect, making the sustained-release rate of the capsule more reasonable; the capsules prepared in Comparative Example 4 have a certain sustained-release effect, but the dissolution rate at the 4th hour has reached 95%, and the sustained-release effect is not significant, indicating that only specific hydroxypropyl methylcellulose can make the sustained-release effect of the capsule better; the capsules prepared in Comparative Example 5 have a dissolution rate of only 43% at the 4th hour, and the release rate is too slow, which is not conducive to the onset of drug effect, and the dissolution rate at the 10th hour is only 76%, and the drug is not completely released; in Comparative Example 6, the ratio of hydroxypropyl methylcellulose and hydroxypropyl cellulose is adjusted, and its sustained-release effect is not obvious; Comparative Example 7 adopts a direct mixing process, and the sustained-release effect of cefadroxil capsules is not significant enough.

[0141] In summary, the cefoperazone capsules of the present invention comprise quick-release granules and sustained-release granules. The quick-release granules can rapidly reach an effective steady-state blood drug concentration, so that the drug can produce an antibacterial effect as quickly as possible and prevent the development of drug resistance; the sustained-release granules can avoid the "peak and valley" phenomenon caused by frequent administration of ordinary preparations, and reduce the number of medications, which greatly facilitates patients.

[0142] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A cefadroxil capsule, characterized in that: The invention comprises quick-release granules, slow-release granules and a lubricant. The slow-release granules comprise cefuroxil, hydroxypropyl cellulose, hydroxypropyl methylcellulose, a filler and a binder. The weight ratio of the hydroxypropyl cellulose to the hydroxypropyl methylcellulose is 1:2-10.

2. The cefadroxil capsule according to claim 1, characterized in that The model of the hydroxypropyl cellulose is HXF or EXF.

3. The cefoperazone capsule according to claim 1, characterized in that: The hydroxypropoxy content of the hypromellose is 4-12%, and the average molecular weight of the hypromellose is 75000-140000.

4. The cefoperazone capsule according to claim 3, characterized in that: The model of the hypromellose is K100M or K100LV.

5. The cefoperazone capsule according to claim 1, characterized in that: The filler is selected from one or more of microcrystalline cellulose, starch and mannitol, and the binder is selected from one or more of povidone, copovidone and ethyl cellulose.

6. The cefoperazone capsule according to claim 1, characterized in that: The rapid-release granules include cefoperazone and a disintegrant, wherein the disintegrant is selected from one or more of sodium carboxymethyl starch, cross-linked sodium carboxymethyl cellulose and cross-linked polyvinylpyrrolidone, and the lubricant is selected from one or more of magnesium stearate, talc and colloidal silicon dioxide.

7. The cefoperazone capsule according to claim 6, characterized in that The cefadroxil capsules include the following components in parts by mass: Immediate-release granules: 120-130 parts of cefadroxil and 0-5 parts of disintegrant; Sustained-release granules: 360-390 parts of cefadroxil, 20-50 parts of hydroxypropyl cellulose, 130-180 parts of hypromellose, 20-60 parts of filler and 1-10 parts of binder; Lubricant: 1-5 parts.

8. The cefoperazone capsule according to claim 6, characterized in that: The cefoperazone capsule further comprises pharmaceutically acceptable excipients.

9. A method for preparing the cefoperazone capsule according to any one of claims 6 to 8, characterized in that: The steps include: (1) firstly mix cefadroxil, hydroxypropyl cellulose, hypromellose and a filler, and then add a binder to obtain sustained-release granules; (2) mixing cefadroxil with a disintegrant to obtain immediate-release granules; (3) Mix the sustained-release granules and the immediate-release granules, add a lubricant, and fill the capsules to obtain the product.

10. Use of the cefoperazone capsule according to any one of claims 6 to 8 or the cefoperazone capsule prepared by the preparation method according to claim 9 in the preparation of antibiotic drugs.

Images