Cefadroxil tablet and its preparation method
By employing dry granulation and adding internal and external excipients, the hydrolysis and tableting performance issues of cefadroxil tablets were resolved, resulting in the preparation of cefadroxil tablets with high stability and good uniformity. This addresses the problems of drug degradation and poor tableting performance in existing technologies.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- YICHANG SANXIA PHARM CO LTD
- Filing Date
- 2026-04-30
- Publication Date
- 2026-07-14
AI Technical Summary
In the existing technology, cefadroxil tablets have problems such as drug degradation, thermal degradation and poor tableting performance due to hydrolysis reaction during the preparation process. In addition, the direct compression method of powder has problems such as large differences in tablet weight, low hardness and unqualified brittleness.
The product employs a dry granulation process, with internal and external binders and flow aids, and uses excipients such as microcrystalline cellulose, crospovidone, and magnesium stearate. Through dry granulation and tableting, hydrolysis is avoided, particle binding is enhanced, and tableting performance and uniformity are improved.
Dry granules with good compression performance, high uniformity, and suitable flowability were prepared, which avoided drug degradation, improved the stability and mechanical properties of cefadroxil tablets, and reduced brittleness.
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Abstract
Description
Technical Field
[0001] This invention belongs to the field of pharmaceutical preparation technology, specifically relating to a cefadroxil tablet and its preparation method. Background Technology
[0002] Cefadroxil is a β - Cephalosporins are cephalosporin antibiotics with good antibacterial activity against Gram-positive bacteria. Clinically, they are mainly used for urinary tract infections, respiratory tract infections, and skin and soft tissue infections caused by susceptible bacteria. They are white or off-white crystalline powders with a characteristic odor, slightly soluble in water, and practically insoluble in ethanol or ether. The most significant characteristic of cefadroxil is its excellent oral absorption, which is not significantly affected by food. Therefore, it is formulated into tablets for more flexible administration and improved compliance. Tablets also facilitate carrying, storage, and maintain good stability, while offering the convenience of granules and syrups in terms of absorption and bioavailability.
[0003] Currently, the main method for preparing cefadroxil tablets is wet granulation. For example, Chinese patent CN104800177B discloses a method for preparing cefadroxil tablets, which involves mixing cefadroxil with microcrystalline cellulose and sodium carboxymethyl starch to obtain a mixed powder. Simultaneously, starch is steamed with water to obtain a starch slurry. The mixed powder and starch slurry are then mixed evenly to obtain a soft mass, which is then sieved, dried, and processed to obtain cefadroxil granules. This invention has the advantages of high product dissolution and short disintegration time. However, in the presence of water, the β-lactam ring in the cefadroxil molecule is prone to hydrolysis. Even during the drying stage, residual moisture may continue to induce slow hydrolysis during storage, leading to excessive levels of related substances (degradation products). At the same time, a drying step is necessary after wet granulation to remove moisture, which usually requires heating the granules to 50°C-60°C or even higher. However, cefadroxil is heat-sensitive, and prolonged heating can lead to a decrease in drug content, the generation of specific thermal degradation impurities, and yellowing of tablets. Therefore, direct powder compression or dry granulation is increasingly preferred for cefadroxil.
[0004] Chinese patent CN111467316A discloses a cefadroxil dispersible tablet and its preparation method. The method involves sieving the raw materials, weighing cefadroxil, filler, and disintegrant according to the prescribed amounts, mixing them thoroughly, adding magnesium stearate, mixing again, and then compressing the mixture into tablets using a tableting machine to obtain the cefadroxil dispersible tablet. This invention has advantages such as simple process, stable quality, ease of operation, and suitability for large-scale production.
[0005] However, this direct powder compression method often suffers from problems such as significant tablet weight variations, low tablet hardness, loose tablets, cracking, and cap loss, leading to substandard friability. Furthermore, an imbalance in the proportions of fillers, disintegrants, and binders can result in material stratification, high friability, and insufficient interparticle bonding. Therefore, to ensure adequate dissolution and rapid disintegration, it is often necessary to supplement binders and strong disintegrants, and to strictly control the particle size of raw materials and excipients to prevent stratification. This ultimately leads to an increase in the amount of binders and disintegrants used. Therefore, obtaining dry granules with good compression performance, high uniformity, and suitable flowability is the core issue in the preparation of cefadroxil tablets. Summary of the Invention
[0006] To address the aforementioned technical problems, this invention provides a cefadroxil tablet and its preparation method, which yields dry granules with good tableting performance, high uniformity, and suitable flowability, thereby preparing cefadroxil tablets with acceptable friability.
[0007] To achieve the above objectives, the present invention provides a cefadroxil tablet, which is composed of the following raw materials in parts by weight: 48-56 parts of cefadroxil, 28-38 parts of filler, 1-7 parts of disintegrant, 0.6-1.4 parts of lubricant, 0.6-1.4 parts of flow aid, 1-5 parts of flavoring agent and 2-8 parts of binder.
[0008] The filler is any one of microcrystalline cellulose, lactose, or starch; the disintegrant is any one of crospovidone, sodium carboxymethyl starch, or sodium crospovidone carboxymethyl cellulose; the lubricant is magnesium stearate or sodium stearate fumarate; the flow aid is any one of silica or talc; the flavoring agent is any one of chicken liver powder or flavoring; and the binder is any one of povidone or hydroxypropyl methylcellulose.
[0009] More preferably, the flavoring is beef flavoring that has passed through an 80-mesh sieve.
[0010] This invention also provides a method for preparing cefadroxil tablets, comprising the following steps:
[0011] (1) Pretreatment: Cefalexin, filler, disintegrant, lubricant, binder, flow aid and flavoring agent are sieved separately; (2) Take the sieved cefadroxil and premix it with filler, disintegrant, flow aid, flow aid and flavoring agent to obtain the first mixture; (3) Add lubricant to the first mixture and premix twice to obtain the second mixture; (4) Dry granulation of the second mixture to obtain dry granules, and calculate the yield of dry granules; (5) The dry granules are mixed with the glidant and binder, then mixed with the lubricant and compressed into tablets to obtain cefazolin tablets.
[0012] Preferably, the amount of the gliding agent added in step (2) is 45-55% of the total gliding agent amount, the amount of the adhesive added is 50% of the total adhesive mass, and the amount of the lubricant added in step (3) is 45-55% of the total lubricant amount.
[0013] Preferably, the formula for calculating the yield of dry granules in step (4) is: yield = total amount of raw materials / actual mass of dry granules × 100%.
[0014] Preferably, the conditions for dry granulation in step (4) are: feed speed of 30-60 rpm, roller gap of 0.5-1.5 mm, roller pressure of 60-100 bar, roller speed of 6-8 rpm, granulation speed of 100 rpm, and screen mesh size of 16 mesh.
[0015] Preferably, the amount of gliding agent added in step (5) = the total mass of gliding agent - the mass of silica in step (2) × the yield of dry particles; The amount of adhesive added = the total mass of adhesive - the mass of adhesive in step (2) × the yield of dry granules; The amount of lubricant added = the total mass of lubricant - the mass of lubricant in step (3) × the yield of dry particles.
[0016] Preferably, the conditions for total mixing in step (5) are mixing at 10-30 rpm for 1-3 min.
[0017] Preferably, the tableting conditions in step (5) are: tableting pressure of 50-90N and tableting speed of 2kT / h-4kT / h.
[0018] Preferably, the sieve mesh size in step (1) is 10-30 mesh; the conditions for the first premixing in step (2) are mixing at 10-30 rpm for 8-12 min; and the conditions for the second premixing in step (3) are mixing at 10-30 rpm for 1-3 min.
[0019] The beneficial effects of this invention are as follows: 1. The silica, binder, and chicken liver powder are divided into internal and external additives. The internal additive is first premixed with cefadroxil and other excipients and then dry granulated. After the dry granules are prepared, the external additive is added to complete the tableting. The dry granulation process avoids the chemical degradation reactions such as hydrolysis or ring-opening of the β-lactam ring in the cefadroxil molecule during wet granulation and other processes, thus avoiding the risks of drug degradation and reduced stability.
[0020] 2. The addition of internal and external binders enhances the agglomeration strength of dry granules and improves the mechanical properties of tablets; the addition of internal and external silica and magnesium stearate reduces the internal friction of granules, improves compressibility, reduces brittleness, and prevents materials from sticking to the inner wall of the equipment and the stirring paddle; this invention significantly improves the tableting performance, uniformity, and flowability of cefadroxil tablets during the preparation process. Detailed Implementation
[0021] The technical solution of the present invention will be further explained and described below with reference to specific embodiments. It is worth noting that the following embodiments are only preferred embodiments of the present invention and should not be construed as limiting the present invention. The scope of protection of the present invention should be determined by the contents of the claims. Modifications and substitutions made by those skilled in the art to the technical solution of the present invention without creative effort all fall within the scope of protection of the present invention.
[0022] The particle size of cefadroxil is 100 μm, the particle size of microcrystalline cellulose SH-200 is 150 μm, the particle size of cross-linked povidone is 150 μm, the particle size of silica (gas phase) is 100 μm, the particle size of povidone K30 is 150 μm, and the particle size of chicken liver powder is 150 μm.
[0023] Example 1 (1) Cefadroxil, microcrystalline cellulose SH-200, crospovidone, silica, povidone K30 and chicken liver powder were sieved through an 80-mesh sieve; (2) Take 50 parts by weight of cefadroxil, 30 parts by weight of microcrystalline cellulose SH-200, 2 parts by weight of cross-linked polyvinylpyrrolidone, 0.3 parts by weight of silica, 1 part by weight of polyvinylpyrrolidone K30, 2 parts by weight of chicken liver powder, and 0.3 parts by weight of magnesium stearate and premix them at 20 rpm for 10 min to obtain the first mixture. (3) The first mixture is added to a dry pellet mill. The parameters are set as follows: feed speed 40 rpm, roller gap 1.0 mm, roller pressure 80 bar, roller speed 7 rpm, and pelletizing speed 100 rpm. The pellets are then sieved through a 16-mesh screen to obtain dry pellets. The yield of dry pellets is calculated using the formula: total mass of dry pellets / total mass of added materials × 100%. (4) Add 0.3 parts by weight of silica and 1 part by weight of polyvinyl ketone K30 to the obtained granules and premix for 10 min at 20 rpm to obtain a second mixture; (5) Add 0.3 parts by weight of magnesium stearate to the second mixture, premix for 2 minutes at 20 rpm to obtain the third mixture, and then transfer it to the tablet press. Compress the tablets to a hardness of 70 N and a tablet weight of 240 mg to obtain cefazolin tablets.
[0024] Example 2 (1) Cefadroxil, microcrystalline cellulose SH-200, sodium carboxymethyl starch, talc, hydroxypropyl methylcellulose, and chicken liver powder were sieved through an 80-mesh sieve; (2) Take 54 parts by weight of cefadroxil, 36 parts by weight of microcrystalline cellulose SH-200, 4 parts by weight of sodium carboxymethyl starch, 0.5 parts by weight of talc, 3 parts by weight of hydroxypropyl methylcellulose, 5 parts by weight of chicken liver powder, and 0.4 parts by weight of sodium stearate and premix them at 30 rpm for 8 min to obtain the first mixture. (3) The first mixture is added to a dry pellet mill. The parameters are set as follows: feed speed 40 rpm, roller gap 1.0 mm, roller pressure 80 bar, roller speed 7 rpm, and pelletizing speed 100 rpm. The pellets are then sieved through a 16-mesh screen to obtain dry pellets. The yield of dry pellets is calculated using the formula: total mass of dry pellets / total mass of added materials × 100%. (4) Add 0.5 parts by weight of talc powder and 3 parts by weight of hydroxypropyl methylcellulose to the obtained granules and premix twice at 30 rpm for 8 min to obtain the second mixture; (5) Add 0.5 parts by weight of sodium stearate fumarate to the second mixture, premix for 1 min at 30 rpm to obtain the third mixture, and then transfer it to the tablet press to compress the tablets with a hardness of 70 N and a tablet weight of 240 mg to obtain cefazolin tablets.
[0025] Example 3 (1) Cefadroxil, microcrystalline cellulose SH-200, croscarmellose sodium, silica, povidone K30 and chicken liver powder were sieved through a 20-mesh sieve; (2) Take 48 parts by weight of cefadroxil, 28 parts by weight of microcrystalline cellulose SH-200, 1 part by weight of cross-linked sodium carboxymethyl cellulose, 0.7 parts by weight of silica, 4 parts by weight of povidone K30, 2 parts by weight of chicken liver powder, and 0.7 parts by weight of magnesium stearate and premix them at 10 rpm for 12 min to obtain the first mixture. (3) The first mixture is added to a dry pellet mill. The parameters are set as follows: feed speed 40 rpm, roller gap 1.0 mm, roller pressure 80 bar, roller speed 7 rpm, and pelletizing speed 100 rpm. The pellets are then sieved through a 16-mesh screen to obtain dry pellets. The yield of dry pellets is calculated using the formula: total mass of dry pellets / total mass of added materials × 100%. (4) Add 0.7 parts by weight of silica and 4 parts by weight of polyvinyl ketone K30 to the obtained granules and premix for 12 min at 10 rpm to obtain the second mixture; (5) Add 0.6-0.7 parts by weight of magnesium stearate to the second mixture, premix it twice at 10-30 rpm for 1-3 min to obtain the third mixture, and then transfer it to the tablet press. Compress it to obtain cefazolin tablets with a hardness of 70 N and a tablet weight of 240 mg.
[0026] Comparative Example 1 (1) Cefadroxil, microcrystalline cellulose SH-200, crospovidone, silica, povidone K30 and chicken liver powder were sieved through an 80-mesh sieve; (2) Take 50 parts by weight of cefadroxil, 20 parts by weight of microcrystalline cellulose SH-200, 2 parts by weight of cross-linked polyvinylpyrrolidone, 0.6 parts by weight of silica, 2 parts by weight of polyvinylpyrrolidone K30, and 2 parts by weight of chicken liver powder and premix them at 10-30 rpm for 8-12 minutes to obtain the first mixture. (3) Add the first mixture into the dry granulator and set the parameters as follows: feed speed 40 rpm, roller gap 1.0 mm, roller pressure 80 bar, roller speed 7 rpm, and granulation speed 100 rpm. Finally, granulate the mixture through a 16-mesh sieve to obtain dry granules. (4) Add 0.6 parts by weight of magnesium stearate to the obtained dry granules and premix twice at 20 rpm for 2 min to obtain the second mixture; (5) Place the dry granules into a tablet press and compress them to achieve a hardness of 70 N and a tablet weight of 240 mg to obtain cefazolin tablets.
[0027] Comparative Example 2 The method and steps are the same as in Example 1, except that silicon dioxide, polyvinylpyrrolidone K30 and magnesium stearate are not added in step (2) to prepare cefadroxil tablets.
[0028] Comparative Example 3 The method and steps are the same as in Example 1, except that the amount of silica added in step (2) is changed to 2 parts by weight, the amount of povidone K30 added is changed to 10 parts by weight, and the amount of magnesium stearate added is changed to 2 parts by weight, so as to prepare cefuroxime tablets.
[0029] Comparative Example 4 The method and steps are the same as in Example 1, except that the amount of silica added in step (2) is changed to 0.6 parts by weight, and no silica is added in step (4) to prepare cefadroxil tablets.
[0030] Comparative Example 5 The method and steps are the same as in Example 1, except that the amount of povidone K30 added in step (2) is changed to 2 parts by weight, and povidone K30 is not added in step (4) to prepare cefadroxil tablets.
[0031] Comparative Example 6 The method and steps are the same as in Example 1, except that the amount of magnesium stearate added in step (2) is changed to 0.6 parts by weight, and magnesium stearate is not added in step (5) to prepare cefadroxil tablets.
[0032] Example 4 A total of approximately 800 tablets from nine different batches prepared in the above examples and comparative examples were taken. The tablet weight and cefadroxil content per tablet were measured, and the friability was statistically analyzed. The results are shown in Table 1. Table 1. Detection results of cefadroxil tablets
[0033] Table 2. Detection results of cefadroxil tablets
[0034] The results, as shown in Table 1, indicate that compared to the comparative example, the example has a lower relative standard deviation and a more stable average tablet weight. Excessive silica and magnesium stearate affect the overall hardness and brittleness of the tablets during compression. While excessive povidone K30 increases the hardness and reduces brittleness of the tablets, it also reduces the flowability of the intermediate particles, affecting the average tablet weight. When binders, flow aids, and lubricants are added in the above proportions and granulation and compression are performed using an internal and external addition method, the flowability and compressibility of the intermediate particles can be improved to a certain extent, thus improving the tablet quality.
Claims
1. A cefalexin tablet, characterized in that: It is composed of the following raw materials in parts by weight: 48-56 parts of cefadroxil, 28-38 parts of filler, 1-7 parts of disintegrant, 0.6-1.4 parts of lubricant, 0.6-1.4 parts of flow aid, 1-5 parts of flavoring agent and 5-10 parts of binder.
2. The cefadroxil tablet according to claim 1, characterized in that: The filler is any one of microcrystalline cellulose, lactose, or starch; the disintegrant is any one of crospovidone, sodium carboxymethyl starch, or sodium crospovidone carboxymethyl cellulose; the lubricant is magnesium stearate or sodium stearate fumarate; the flow aid is any one of silica or talc; the flavoring agent is any one of chicken liver powder or flavoring; and the binder is any one of povidone or hydroxypropyl methylcellulose.
3. A method for preparing cefadroxil tablets as described in claim 1 or 2, characterized in that: Includes the following steps: (1) Pretreatment: Cefalexin, filler, disintegrant, lubricant, binder, flow aid and flavoring agent are sieved separately; (2) Take the sieved cefadroxil and premix it with filler, disintegrant, flow aid, binder and flavoring agent to obtain the first mixture; (3) Add lubricant to the first mixture and premix twice to obtain the second mixture; (4) Dry granulation of the second mixture to obtain dry granules, and calculate the yield of dry granules; (5) The dry granules are mixed with the glidant and binder, then mixed with the lubricant and compressed into tablets to obtain cefazolin tablets.
4. The preparation method according to claim 3, characterized in that: The amount of gliding agent added in step (2) is 45-55% of the total amount of gliding agent, the amount of adhesive added is 50% of the total amount of adhesive, and the amount of lubricant added in step (3) is 45-55% of the total amount of lubricant.
5. The preparation method according to claim 3, characterized in that: The formula for calculating the yield of dry granules in step (4) is: yield = total amount of raw materials / actual mass of dry granules × 100%.
6. The preparation method according to claim 3, characterized in that: The conditions for dry granulation in step (4) are: feed speed of 30-60 rpm, roller gap of 0.5-1.5 mm, roller pressure of 60-100 bar, roller speed of 6-8 rpm, granulation speed of 100 rpm, and screen mesh size of 16 mesh.
7. The preparation method according to claim 3, characterized in that: The amount of gliding agent added in step (5) = the total mass of gliding agent - the mass of silica in step (2) × the yield of dry particles; The amount of adhesive added = the total mass of adhesive - the mass of adhesive in step (2) × the yield of dry granules; The amount of lubricant added = the total mass of lubricant - the mass of lubricant in step (3) × the yield of dry particles.
8. The preparation method according to claim 3, characterized in that: The conditions for total mixing in step (5) are to mix at 15-30 rpm for 1-3 min.
9. The preparation method according to claim 3, characterized in that: The tableting conditions described in step (5) are: tableting pressure of 50-90N and tableting speed of 2kT / h-4kT / h.
10. The preparation method according to claim 3, characterized in that: The sieve used in step (1) has a mesh size of 10-30; the conditions for the first premixing in step (2) are mixing at 10-30 rpm for 8-12 min; and the conditions for the second premixing in step (3) are mixing at 10-30 rpm for 1-3 min.