A cefprozil dry suspension and its preparation method

Abstract

This invention belongs to the technical field of cefprozil dry suspension, specifically relating to a cefprozil dry suspension and its preparation method. The cefprozil dry suspension comprises the following raw materials: cefprozil, molecular sieve agent, hygroscopic agent, excipient, and suspending agent; the molecular sieve agent is silica; the hygroscopic agent includes at least one of silica gel and silica; and the excipient includes at least one of a surface modifier, a carrier, and a flavoring agent. Preparation method: The cefprozil dry suspension is prepared by spray granulation. First, the molecular sieve agent, cefprozil, carrier, and hygroscopic agent are mixed evenly. Then, the surface modifier, suspending agent, and flavoring agent are added and mixed evenly to obtain a mixture. The mixture is then spray-dried and granulated to obtain the cefprozil dry suspension. This invention can improve the stability, dispersibility, and solubility of the cefprozil dry suspension.

Description

Technical Field

[0001] This invention belongs to the technical field of cefprozil dry suspension, specifically relating to a cefprozil dry suspension and its preparation method. Background Technology

[0002] Cefprozil, as a second-generation cephalosporin, has a significant broad-spectrum antibacterial effect and is beneficial in inhibiting bacterial cell wall synthesis.

[0003] Dry suspensions are mixtures of solid powders or granules that need to be diluted with water or other diluents before use. They are typically formulated as dry suspensions because the chemical or physical stability of the active pharmaceutical ingredient (API) cannot meet requirements within its shelf life, thus extending its shelf life.

[0004] The difficulty in preparing cefprozil dry suspension lies in:

[0005] 1. Stability issues: Cefprozil dry suspension may lose stability during prolonged storage or under inappropriate storage conditions, which may lead to drug degradation or particle clumping, affecting its efficacy and use.

[0006] 2. Dispersibility issues: The dispersibility of particles is crucial to the effectiveness of dry suspensions. Poor dispersibility may result in cefprozil dry suspension particles not being uniformly dispersed in the solvent during reconstitution.

[0007] 3. Solubility issues: If the cefprozil raw material is not fully dissolved in the mixture before formulation, it may affect the release rate and effectiveness of the cefprozil dry suspension. Summary of the Invention

[0008] The purpose of this invention is to provide a cefprozil dry suspension. This invention improves the stability, dispersibility, and solubility of the cefprozil dry suspension.

[0009] A cefprozil dry suspension comprises the following raw materials: cefprozil, molecular sieve agent, hygroscopic agent, excipient, and suspending agent; wherein the molecular sieve agent is silica; and the hygroscopic agent comprises at least one of silica gel and silica.

[0010] Using the above technical solution, the hygroscopic agent helps absorb moisture and prevents cefprozil from clumping or degrading in the dry suspension. This application selects silica as the molecular sieve agent. Silica is a porous material, and its porous structure allows for the adsorption and retention of water molecules, preventing water from degrading the drug. The molecular sieve agent has active sites on its surface that can adsorb water molecules, reducing the risk of water decomposition of cefprozil.

[0011] Preferably, the excipient includes at least one of a surface modifier, a carrier, and a flavoring agent.

[0012] Preferably, the carrier includes at least one of methylcellulose and sodium carboxymethylcellulose.

[0013] By adopting the above technical solution, adding a carrier can enhance the hygroscopicity and dispersibility of the particles, ensuring that the dry suspension can be rapidly and uniformly dispersed in the solvent when reconstituted. In this application, methylcellulose and / or sodium carboxymethylcellulose are selected. Methylcellulose and / or sodium carboxymethylcellulose form a colloid in the system. Using the colloidal form as a carrier for cefprozil not only synergistically enhances hygroscopicity and dispersibility, but also enables the active ingredient of the drug (cefprozil) to become a sustained-release system.

[0014] Preferably, the flavoring agent includes at least one of mango cellulose, sucrose, glucose, fructose, and lactose, wherein the mango cellulose is cellulose extracted from mango.

[0015] Using the above technical solution, mango cellulose can be used as a food additive and food coloring. Mango cellulose is a water-soluble cellulose extracted from mangoes and is safer than artificial sweeteners.

[0016] Preferably, the surface modifier includes at least one of polyvinylpyrrolidone and silicone oil.

[0017] Using the above technical solution, the surface modifier covers the particle surface, reducing the adsorption force between particles and making the finished particles easier to disperse in heavy solutions. Surface modification can also synergize with other raw materials, making the particles easier to redissolve and improving the efficacy of the drug. This application selects polyvinylpyrrolidone and / or silicone oil as surface modifiers, which have hydrophilic functional groups. These groups can interact with the surface of cefprozil particles, and can also interact with water molecules, thereby reducing the affinity difference between particles and making the particles easier to disperse in water.

[0018] Preferably, the suspending agent includes at least one of methylcellulose, sodium carboxymethylcellulose, cellulose acetate, and polyethylene glycol.

[0019] Preferably, the cefprozil dry suspension comprises the following raw materials in parts by weight: 100 parts by weight of cefprozil, 1-5% by weight of hygroscopic agent, 2-5% by weight of silica, and 8-20% by weight of excipients and suspending agents.

[0020] Preferably, the cefprozil is 100 parts by weight, the surface modifier is 1-3% by weight of cefprozil, the flavoring agent is 5-10% by weight of cefprozil, the carrier is 1-2% by weight of cefprozil, and the suspending agent is 1-5% by weight of cefprozil.

[0021] By employing the above technical solution, excessive moisture absorption is prevented by adjusting the proportion of the desiccant, while maintaining sufficient hygroscopicity to preserve particle flowability. The porosity and surface area of ​​the molecular sieve agent enable it to adsorb and store water molecules, preventing water from reacting with cefprozil, degrading, or agglomerating. The selection and dosage of the molecular sieve agent affect its adsorption capacity and efficacy, thus requiring precise control.

[0022] The second objective of this invention is to provide a method for preparing the cefprozil dry suspension, wherein the cefprozil dry suspension is prepared by spray granulation. First, the molecular sieve agent, the cefprozil, the carrier, and the hygroscopic agent are mixed evenly. Then, the surface modifier, the suspending agent, and the flavoring agent are added and mixed evenly to obtain a mixture. The mixture is then spray-dried and granulated to obtain the cefprozil dry suspension.

[0023] Using the above technical solution, the particles are prepared by spray drying technology. Combined with the formulation of this application, this method helps to improve the dispersibility of the particles, making them easy to resuspend before use. Cefprozil is first carried by the carrier, the molecular sieve agent plays a role similar to a "skeleton", and the hygroscopic agent is dispersed in the system to enhance the dispersibility of the system.

[0024] Preferably, the mixing time is 10 to 30 minutes.

[0025] Using the above technical solution, during this process, the mixture is sprayed into small particles using a spray granulation method and then dried to prepare the finished granules of cefprozil dry suspension.

[0026] The beneficial effects of this invention are:

[0027] First, the formulation of this invention is superior. Specifically, the formulation includes cefprozil, molecular sieve agent, hygroscopic agent, excipient, and suspending agent. The excipient includes surface modifier, carrier, and flavoring agent. The absence of any one of these components has a relatively small impact on the finished product granules in the short term, but over time, the overall performance (including hygroscopicity, resolubility, and dissolution rate) decreases significantly, which is detrimental to storage and reduces the medicinal properties. Furthermore, the finished product of this invention exhibits superior performance compared to commercially available products using existing technologies.

[0028] Second, the present invention further optimizes the formulation, specifically as follows: (1) Optimal weight parts: molecular sieve agent preferably 3 parts, hygroscopic agent preferably 3 parts, surface modifier preferably 2 parts, carrier preferably 2 parts, and suspending agent preferably 3 parts. (2) Optimal components: flavoring agent preferably mango cellulose, hygroscopic agent preferably silica gel, and the finished product particles prepared with silicone oil in the surface modifier have smaller particle size, while the finished product particles prepared with polyvinylpyrrolidone have better resolubility. (3) The present invention controls the proportion of each component, which can maintain sufficient hygroscopicity to maintain the flowability of the particles and prevent excessive moisture absorption.

[0029] Third, this application selects silica as a molecular sieve agent. Silica is a porous material, and its porous structure allows for the adsorption and retention of water molecules, preventing water from degrading the drug. The surface of the molecular sieve agent has active sites that can adsorb water molecules, reducing solubility and thus reducing the risk of water decomposition of cefprozil. Hygroscopic agents help absorb moisture, preventing cefprozil from clumping or degrading in dry suspensions. Surface modifiers cover the particle surface, changing surface properties and reducing the adsorption force between particles, making the finished particles easier to disperse in heavy solutions. After improving dispersibility, surface modification can also synergize with other raw materials, making the particles easier to resuspend and disperse in heavy solutions, thus improving drug efficacy. This application selects polyvinylpyrrolidone and / or silicone oil as surface modifiers, which have hydrophilic functional groups. These can interact with the surface of cefprozil particles, and the hydrophilic functional groups can also interact with water molecules, thereby reducing the affinity difference between particles and making the particles easier to disperse in water. Adding a carrier can enhance the hygroscopicity and dispersibility of particles, ensuring that the suspension can be rapidly and uniformly dispersed in a suitable solvent upon reconstitution. This application uses methylcellulose and / or sodium carboxymethylcellulose. Methylcellulose and / or sodium carboxymethylcellulose form a colloid in the system. Using this colloidal form as a carrier for cefprozil not only synergistically enhances hygroscopicity and dispersibility but also enables the active pharmaceutical ingredient (cefprozil) to be released in a sustained-release system. Flavoring agents include mango cellulose, sucrose, glucose, fructose, and lactose. Mango cellulose is commonly used as a food additive and food coloring. Mango cellulose is a water-soluble cellulose extracted from mangoes and is safer than artificial sweeteners.

[0030] Fourth, this invention also tested the flavoring agents by varying their types and weights, selecting 5 parts for each agent and the optimal weights for all other ingredients. The results showed that the five flavoring agents had little difference in their impact on the finished product, with mango cellulose being the most effective. The combination of mango cellulose with the molecular sieve agent, surface modifier, carrier, and suspending agent yielded the best results and optimal synergistic performance. Cefprozil is first carried by the carrier, the molecular sieve agent acts as a "skeleton," and the hygroscopic agent disperses in the system, enhancing its dispersibility. Mango cellulose better complexes the colloid formed by the carrier, enhancing the bond between cefprozil and the carrier. Other synergistic effects have been explained above.

[0031] In summary, this invention can improve the stability, dispersibility, and solubility of cefprozil dry suspension. Detailed Implementation

[0032] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0033] Unless otherwise specified, the reagents used in the examples can be readily obtained from commercial companies or prepared in-house.

[0034] in,

[0035] Mango cellulose was purchased from Fufeng Sinote Biotechnology Co., Ltd.

[0036] Spray drying granulation machine, Changzhou Suli Drying Equipment Co., Ltd.

[0037] Note: The parts in the formula of this invention are parts by weight.

[0038] Table 1

[0039]

[0040]

[0041] Example 1

[0042] A cefprozil dry suspension and its preparation method are as follows:

[0043] Referring to the mass fractions in Table 1, cefprozil dry suspension was prepared by spray granulation. First, molecular sieve agent, cefprozil, carrier, hygroscopic agent and solvent (purified water) were put into a spray dryer and mixed evenly for 10 min. Then, surface modifier, suspending agent and flavoring agent were added and mixed evenly for 10 min to obtain a mixture. The mixture was spray dried for 11 s until the moisture content of the particles was 0.2-1%. The particles were then granulated and packaged to obtain cefprozil dry suspension.

[0044] Example 2

[0045] A cefprozil dry suspension and its preparation method are as follows:

[0046] Referring to the mass fractions in Table 1, cefprozil dry suspension was prepared by spray granulation. First, molecular sieve agent, cefprozil, carrier, hygroscopic agent and solvent (purified water) were put into a spray dryer and mixed evenly for 11 min. Then, surface modifier, suspending agent and flavoring agent were added and mixed evenly for 10 min to obtain a mixture. The mixture was spray dried for 11 s until the moisture content of the particles was 0.2-1%. The mixture was then granulated and packaged to obtain cefprozil dry suspension.

[0047] Example 3

[0048] A cefprozil dry suspension and its preparation method are as follows:

[0049] Referring to the mass fractions in Table 1, cefprozil dry suspension was prepared by spray granulation. First, molecular sieve agent, cefprozil, carrier, hygroscopic agent and solvent (purified water) were placed into a spray dryer and mixed evenly for 12 min. Then, surface modifier, suspending agent and flavoring agent were added and mixed evenly for 10 min to obtain a mixture. The mixture was spray dried for 11 s until the particle moisture content was 0.2-1%. Granulation and packaging were then performed to obtain cefprozil dry suspension.

[0050] The cefprozil dry suspensions of Examples 1-3 were tested, and the results are shown in Tables 2 and 3 below.

[0051] Testing items and requirements:

[0052] (1) Particle size: The particle size of the dispersed phase is detected by a laser particle size analyzer, and is required to be within 0.5–0.71 μm.

[0053] (2) Hygroscopicity test: Place the granules at 40℃±2℃ and 75%±5% relative humidity for 15 days and observe whether the granules change color and / or clump together.

[0054] (3) Redissolution test: Take 0.125g of dry suspension for each example and place it in a 50ml graduated cylinder. Stir for 1 minute and observe whether the sediment at the bottom of the graduated cylinder is redispersed evenly.

[0055] (4) Dissolution: Using 900 ml of water as the dissolution medium and a rotation speed of 75 rpm, after 30 minutes, take an appropriate amount of the solution, filter it, and use the filtrate as the test solution; separately take an appropriate amount of cefprozil reference standard (cefprozil dry suspension, Yihua, comparative example 1), dissolve it in water and quantitatively dilute it to prepare a solution containing 0.14 mg per ml, as the reference solution. Place it under the conditions of 40℃±2℃ and 75%±5% relative humidity for 15 days, and calculate the dissolution rate. The requirement is ≥80%.

[0056] Table 2

[0057]

[0058] Table 3

[0059]

[0060] Results Analysis: The particle size, hygroscopicity, resolubility, and dissolution rate of Examples 1-3 of this application all meet the requirements. When only the weight percentage of silica is changed, and all other ingredients are selected to the minimum weight percentage to minimize the impact, Example 2 exhibits the best overall performance, with 3 parts silica being the preferred amount. In the dissolution rate test, the dissolution rates of Examples 1-3 are 12% higher than that of Comparative Example 1, indicating superior performance.

[0061] Table 4

[0062]

[0063]

[0064] Example 4

[0065] A cefprozil dry suspension and its preparation method are as follows:

[0066] Referring to the mass fractions in Table 4, cefprozil dry suspension was prepared by spray granulation. First, molecular sieve agent, cefprozil, carrier, hygroscopic agent and solvent (purified water) were placed into a spray dryer and mixed evenly for 10 min. Then, surface modifier, suspending agent and flavoring agent were added and mixed evenly for 10 min to obtain a mixture. The mixture was spray dried for 11 s until the particle moisture content was 0.2-1%. Granulation and packaging were then performed to obtain cefprozil dry suspension.

[0067] Example 5

[0068] A cefprozil dry suspension and its preparation method are as follows:

[0069] Referring to the mass fractions in Table 4, cefprozil dry suspension was prepared by spray granulation. First, molecular sieve agent, cefprozil, carrier, hygroscopic agent and solvent (purified water) were put into a spray dryer and mixed evenly for 11 min. Then, surface modifier, suspending agent and flavoring agent were added and mixed evenly for 10 min to obtain a mixture. The mixture was spray dried for 11 s until the moisture content of the particles was 0.2-1%. The particles were then granulated and packaged to obtain cefprozil dry suspension.

[0070] Example 6

[0071] A cefprozil dry suspension and its preparation method are as follows:

[0072] Referring to the mass fractions in Table 4, cefprozil dry suspension was prepared by spray granulation. First, molecular sieve agent, cefprozil, carrier, hygroscopic agent and solvent (purified water) were put into a spray dryer and mixed evenly for 12 min. Then, surface modifier, suspending agent and flavoring agent were added and mixed evenly for 10 min to obtain a mixture. The mixture was spray dried for 11 s until the moisture content of the particles was 0.2-1%. The particles were then granulated and packaged to obtain cefprozil dry suspension.

[0073] The cefprozil dry suspensions of Examples 4-6 were tested, and the results are shown in Tables 5 and 6 below.

[0074] The testing items and requirements are the same as those in Examples 1 to 3.

[0075] Table 5

[0076]

[0077]

[0078] Table 6

[0079]

[0080] Results Analysis: The particle size, hygroscopicity, resolubility, and dissolution rate of Examples 4-6 of this application all meet the requirements. When only the weight percentage of silica gel is changed, and the weight percentage of silica gel is set to 2 parts, while other ingredients are selected to the minimum weight percentage to minimize the impact, Example 5 exhibits the best overall performance, with 3 parts silica gel being the preferred choice. In the dissolution test, the dissolution rates of Examples 4-6 are 13% higher than that of Comparative Example 1, indicating superior performance.

[0081] Table 7

[0082]

[0083]

[0084] Example 7

[0085] A cefprozil dry suspension and its preparation method are as follows:

[0086] Referring to the mass fractions in Table 7, cefprozil dry suspension was prepared by spray granulation. First, molecular sieve agent, cefprozil, carrier, hygroscopic agent and solvent (purified water) were put into a spray dryer and mixed evenly for 10 min. Then, surface modifier, suspending agent and flavoring agent were added and mixed evenly for 10 min to obtain a mixture. The mixture was spray dried for 11 s until the moisture content of the particles was 0.2-1%. The particles were then granulated and packaged to obtain cefprozil dry suspension.

[0087] Example 8

[0088] A cefprozil dry suspension and its preparation method are as follows:

[0089] Referring to the mass fractions in Table 7, cefprozil dry suspension was prepared by spray granulation. First, molecular sieve agent, cefprozil, carrier, hygroscopic agent and solvent (purified water) were put into a spray dryer and mixed evenly for 10 min. Then, surface modifier, suspending agent and flavoring agent were added and mixed evenly for 11 min to obtain a mixture. The mixture was spray dried for 11 s until the moisture content of the particles was 0.2-1%. The particles were then granulated and packaged to obtain cefprozil dry suspension.

[0090] Example 9

[0091] A cefprozil dry suspension and its preparation method are as follows:

[0092] Referring to the mass fractions in Table 7, cefprozil dry suspension was prepared by spray granulation. First, molecular sieve agent, cefprozil, carrier, hygroscopic agent and solvent (purified water) were put into a spray dryer and mixed evenly for 10 min. Then, surface modifier, suspending agent and flavoring agent were added and mixed evenly for 12 min to obtain a mixture. The mixture was spray dried for 11 s until the moisture content of the particles was 0.2-1%. The particles were then granulated and packaged to obtain cefprozil dry suspension.

[0093] The cefprozil dry suspensions of Examples 7-9 were tested, and the results are shown in Tables 8 and 9 below.

[0094] The testing items and requirements are the same as those in Examples 1 to 3.

[0095] Table 8

[0096]

[0097] Table 9

[0098]

[0099] Results Analysis: The particle size, hygroscopicity, resolubility, and dissolution rate of Examples 7-9 of this application all meet the requirements. When only the weight percentage of polyvinylpyrrolidone is changed, and the weight percentages of silica are 2 parts, silica gel 1 part, and other ingredients are kept to the minimum weight percentage to minimize the impact, Example 8 exhibits the best overall performance, with 2 parts of polyvinylpyrrolidone being the preferred choice. In the dissolution test, the dissolution rates of Examples 7-9 are higher than that of Comparative Example 1 (13.2%), indicating superior performance.

[0100] Table 10

[0101]

[0102]

[0103] Example 10

[0104] A cefprozil dry suspension and its preparation method are as follows:

[0105] Referring to the mass fractions in Table 10, cefprozil dry suspension was prepared by spray granulation. First, molecular sieve agent, cefprozil, carrier, hygroscopic agent and solvent (purified water) were put into a spray dryer and mixed evenly for 10 min. Then, surface modifier, suspending agent and flavoring agent were added and mixed evenly for 10 min to obtain a mixture. The mixture was spray dried for 11 s until the moisture content of the particles was 0.2-1%. The particles were then granulated and packaged to obtain cefprozil dry suspension.

[0106] Example 11

[0107] A cefprozil dry suspension and its preparation method are as follows:

[0108] Referring to the mass fractions in Table 10, cefprozil dry suspension was prepared by spray granulation. First, molecular sieve agent, cefprozil, carrier, hygroscopic agent and solvent (purified water) were placed into a spray dryer and mixed evenly for 11 min. Then, surface modifier, suspending agent and flavoring agent were added and mixed evenly for 10 min to obtain a mixture. The mixture was spray dried for 11 s until the moisture content of the particles was 0.2-1%. The particles were then granulated and packaged to obtain cefprozil dry suspension.

[0109] Example 12

[0110] A cefprozil dry suspension and its preparation method are as follows:

[0111] Referring to the mass fractions in Table 10, cefprozil dry suspension was prepared by spray granulation. First, molecular sieve agent, cefprozil, carrier, hygroscopic agent and solvent (purified water) were placed into a spray dryer and mixed evenly for 12 minutes. Then, surface modifier, suspending agent and flavoring agent were added and mixed evenly for 10 minutes to obtain a mixture. The mixture was spray dried for 11 seconds until the moisture content of the particles was 0.2-1%. The mixture was then granulated and packaged to obtain cefprozil dry suspension.

[0112] The cefprozil dry suspensions of Examples 10-12 were tested, and the results are shown in Tables 11 and 12 below.

[0113] The testing items and requirements are the same as those in Examples 1 to 3.

[0114] Table 11

[0115]

[0116] Table 12

[0117]

[0118] Results Analysis: The particle size, hygroscopicity, resolubility, and dissolution rate of Examples 10-12 of this application all meet the requirements. When only the weight percentage of methylcellulose is changed, and the weight percentages of silica (2 parts), silica gel (1 part), and polyvinylpyrrolidone (1 part) are selected, while other ingredients are chosen to be in the lowest possible weight percentage, Example 12 exhibits the best overall performance, with 2 parts of methylcellulose being the preferred choice. In the dissolution test, the dissolution rates of Examples 10-12 are 13% higher than that of Comparative Example 1, indicating superior performance.

[0119] Table 13

[0120]

[0121]

[0122] Example 13

[0123] A cefprozil dry suspension and its preparation method are as follows:

[0124] Referring to the mass fractions in Table 13, cefprozil dry suspension was prepared by spray granulation. First, molecular sieve agent, cefprozil, carrier, hygroscopic agent and solvent (purified water) were put into a spray dryer and mixed evenly for 10 min. Then, surface modifier, suspending agent and flavoring agent were added and mixed evenly for 10 min to obtain a mixture. The mixture was spray dried for 11 s until the moisture content of the particles was 0.2-1%. The particles were then granulated and packaged to obtain cefprozil dry suspension.

[0125] Example 14

[0126] A cefprozil dry suspension and its preparation method are as follows:

[0127] Referring to the mass fractions in Table 13, cefprozil dry suspension was prepared by spray granulation. First, molecular sieve agent, cefprozil, carrier, hygroscopic agent and solvent (purified water) were put into a spray dryer and mixed evenly for 10 min. Then, surface modifier, suspending agent and flavoring agent were added and mixed evenly for 11 min to obtain a mixture. The mixture was spray dried for 11 s until the moisture content of the particles was 0.2-1%. The particles were then granulated and packaged to obtain cefprozil dry suspension.

[0128] Example 15

[0129] A cefprozil dry suspension and its preparation method are as follows:

[0130] Referring to the mass fractions in Table 13, cefprozil dry suspension was prepared by spray granulation. First, molecular sieve agent, cefprozil, carrier, hygroscopic agent and solvent (purified water) were put into a spray dryer and mixed evenly for 10 min. Then, surface modifier, suspending agent and flavoring agent were added and mixed evenly for 12 min to obtain a mixture. The mixture was spray dried for 11 s until the moisture content of the particles was 0.2-1%. The particles were then granulated and packaged to obtain cefprozil dry suspension.

[0131] The cefprozil dry suspensions of Examples 13-15 were tested, and the results are shown in Tables 14 and 15 below.

[0132] The testing items and requirements are the same as those in Examples 1 to 3.

[0133] Table 14

[0134]

[0135] Table 15

[0136]

[0137] Results Analysis: The particle size, hygroscopicity, resolubility, and dissolution rate of Examples 13-15 of this application all meet the requirements. When only the weight percentage of sodium carboxymethyl cellulose is changed, and the weight percentages of silica (2 parts), silica gel (1 part), polyvinylpyrrolidone (1 part), and methyl cellulose (1 part) are selected, while other ingredients are chosen to be in the lowest possible weight percentage, Example 14 exhibits the best overall performance, with 3 parts of sodium carboxymethyl cellulose being the preferred choice. In the dissolution rate test, the dissolution rate of Examples 13-15 is 13% higher than that of Comparative Example 1, indicating superior performance.

[0138] Table 16

[0139]

[0140] Example 16

[0141] A cefprozil dry suspension and its preparation method are as follows:

[0142] Referring to the mass fractions in Table 16, cefprozil dry suspension was prepared by spray granulation. First, molecular sieve agent, cefprozil, carrier, hygroscopic agent and solvent (purified water) were put into a spray dryer and mixed evenly for 11 min. Then, surface modifier, suspending agent and flavoring agent were added and mixed evenly for 10 min to obtain a mixture. The mixture was spray dried for 11 s until the moisture content of the particles was 0.2-1%. The mixture was then granulated and packaged to obtain cefprozil dry suspension.

[0143] Example 17

[0144] A cefprozil dry suspension and its preparation method are as follows:

[0145] Referring to the mass fractions in Table 16, cefprozil dry suspension was prepared by spray granulation. First, molecular sieve agent, cefprozil, carrier, hygroscopic agent and solvent (purified water) were put into a spray dryer and mixed evenly for 11 min. Then, surface modifier, suspending agent and flavoring agent were added and mixed evenly for 10 min to obtain a mixture. The mixture was spray dried for 11 s until the moisture content of the particles was 0.2-1%. The mixture was then granulated and packaged to obtain cefprozil dry suspension.

[0146] The cefprozil dry suspensions of Examples 16-17 were tested, and the results are shown in Tables 17 and 18 below.

[0147] The testing items and requirements are the same as those in Examples 1 to 3.

[0148] Table 17

[0149]

[0150] Table 18

[0151]

[0152] Results Analysis: The particle size, hygroscopicity, resolubility, and dissolution rate of Examples 16-17 of this application all meet the requirements. The optimal amounts of silica gel and silica were selected in the smallest possible weight proportions, and other ingredients were selected in the lowest possible weight proportions. With these factors minimized, Example 17 exhibits the best overall performance. Silica gel is preferred over silica gel. In the dissolution test, the dissolution rate of Examples 16-17 is 13% higher than that of Comparative Example 1, indicating superior performance.

[0153] Table 19

[0154]

[0155] Example 18

[0156] A cefprozil dry suspension and its preparation method are as follows:

[0157] Referring to the mass fractions in Table 19, cefprozil dry suspension was prepared by spray granulation. First, molecular sieve agent, cefprozil, carrier, hygroscopic agent and solvent (purified water) were put into a spray dryer and mixed evenly for 10 min. Then, surface modifier, suspending agent and flavoring agent were added and mixed evenly for 11 min to obtain a mixture. The mixture was spray dried for 11 s until the moisture content of the particles was 0.2-1%. The particles were then granulated and packaged to obtain cefprozil dry suspension.

[0158] Example 19

[0159] A cefprozil dry suspension and its preparation method are as follows:

[0160] Referring to the mass fractions in Table 19, cefprozil dry suspension was prepared by spray granulation. First, molecular sieve agent, cefprozil, carrier, hygroscopic agent and solvent (purified water) were put into a spray dryer and mixed evenly for 10 min. Then, surface modifier, suspending agent and flavoring agent were added and mixed evenly for 11 min to obtain a mixture. The mixture was spray dried for 11 s until the moisture content of the particles was 0.2-1%. The particles were then granulated and packaged to obtain cefprozil dry suspension.

[0161] The cefprozil dry suspensions of Examples 18-19 were tested, and the results are shown in Tables 20 and 21 below.

[0162] The testing items and requirements are the same as those in Examples 1 to 3.

[0163] Table 20

[0164]

[0165] Table 21

[0166]

[0167] Results Analysis: The particle size, hygroscopicity, resolubility, and dissolution rate of Examples 18-19 of this application all meet the requirements. The optimal amounts of polyvinylpyrrolidone and silicone oil were selected in two parts each, and the minimum weight parts of other ingredients were chosen. With these factors minimized, Example 19 exhibited better resolubility, while Example 18 had a smaller particle size. In the dissolution test, the dissolution rate of Examples 18-19 was higher than that of Comparative Example 1 (13.2%), indicating superior performance.

[0168] Table 22

[0169]

[0170]

[0171] Example 20

[0172] A cefprozil dry suspension and its preparation method are as follows:

[0173] Referring to the mass fractions in Table 22, cefprozil dry suspension was prepared by spray granulation. First, molecular sieve agent, cefprozil, carrier, hygroscopic agent and solvent (purified water) were put into a spray dryer and mixed evenly for 12 min. Then, surface modifier, suspending agent and flavoring agent were added and mixed evenly for 10 min to obtain a mixture. The mixture was spray dried for 11 s until the moisture content of the particles was 0.2-1%. The mixture was then granulated and packaged to obtain cefprozil dry suspension.

[0174] Example 21

[0175] A cefprozil dry suspension and its preparation method are described below. The preparation steps are the same as those in Example 20, referring to the mass parts in Table 22.

[0176] The cefprozil dry suspensions of Examples 20-21 were tested, and the results are shown in Tables 23 and 24 below.

[0177] The testing items and requirements are the same as those in Examples 1 to 3.

[0178] Table 23

[0179]

[0180] Table 24

[0181]

[0182] Results Analysis: The particle size, hygroscopicity, resolubility, and dissolution rate of Examples 20-21 of this application all meet the requirements. The optimal two parts of both methylcellulose and sodium carboxymethylcellulose were selected, while the minimum weight parts of other ingredients were chosen. With the influence minimized, the performance of methylcellulose and sodium carboxymethylcellulose is not significantly different. In the dissolution test, the dissolution rate of Examples 20-21 is 13% higher than that of Comparative Example 1, indicating superior performance.

[0183] Table 25

[0184]

[0185]

[0186] Example 22

[0187] A cefprozil dry suspension and its preparation method are as follows:

[0188] Referring to the mass fractions in Table 25, cefprozil dry suspension was prepared by spray granulation. First, molecular sieve agent, cefprozil, carrier, hygroscopic agent and solvent (purified water) were put into a spray dryer and mixed evenly for 10 min. Then, surface modifier, suspending agent and flavoring agent were added and mixed evenly for 11 min to obtain a mixture. The mixture was spray dried for 11 s until the moisture content of the particles was 0.2-1%. The particles were then granulated and packaged to obtain cefprozil dry suspension.

[0189] The preparation steps of Examples 23-25 ​​are the same as those of Example 22, and the formulas are as shown in Table 25.

[0190] The cefprozil dry suspensions of Examples 22-25 were tested, and the results are shown in Tables 26 and 27 below.

[0191] The testing items and requirements are the same as those in Examples 1 to 3.

[0192] Table 26

[0193]

[0194]

[0195] Table 27

[0196]

[0197] Results Analysis: The particle size, hygroscopicity, resolubility, and dissolution rate of Examples 22-25 of this application all meet the requirements. Methylcellulose, sodium carboxymethyl cellulose, cellulose acetate, and polyethylene glycol are all preferably in parts of 3. Other ingredients are selected in the minimum weight proportions. With minimal impact, the performance differences among the four ingredients are minimal. In the dissolution test, the dissolution rate of Examples 22-25 is 13% higher than that of Comparative Example 1, indicating superior performance.

[0198] Table 28

[0199]

[0200]

[0201] Example 25

[0202] A cefprozil dry suspension and its preparation method are as follows:

[0203] Referring to the mass fractions in Table 28, cefprozil dry suspension was prepared by spray granulation. First, molecular sieve agent, cefprozil, carrier, hygroscopic agent and solvent (purified water) were placed into a spray dryer and mixed evenly for 15 min. Then, surface modifier, suspending agent and flavoring agent were added and mixed evenly for 15 min to obtain a mixture. The mixture was spray dried for 11 s until the particle moisture content was 0.2-1%. Granulation and packaging were then performed to obtain cefprozil dry suspension.

[0204] The preparation steps of Examples 26-29 are the same as those of Example 25, and the formulas are as shown in Table 28.

[0205] The cefprozil dry suspensions of Examples 25-29 were tested, and the results are shown in Tables 29 and 30 below.

[0206] The testing items and requirements are the same as those in Examples 1 to 3.

[0207] Table 29

[0208]

[0209]

[0210] Table 30

[0211]

[0212] Results Analysis: The particle size, hygroscopicity, resolubility, and dissolution rate of Examples 25-29 of this application all meet the requirements. By changing the type of flavoring agent, 5 parts by weight were selected for all five, and the optimal weight parts for the other ingredients were chosen. The differences between the five flavoring agents were minimal, with mango cellulose showing the best performance. The compatibility and synergistic effect of mango cellulose with the molecular sieve agent, surface modifier, carrier, and suspending agent were optimal. In the dissolution test, the dissolution rate of Examples 25-29 was 14% higher than that of Comparative Example 1, indicating superior performance.

[0213] Table 31

[0214]

[0215]

[0216] Table 32

[0217]

[0218] Table 33

[0219]

[0220]

[0221] The preparation methods of Examples 30-35 are the same as those of Example 1, and the preparation methods of Comparative Examples 2-7 are also the same as those of Example 1, except for the specific formulations, which are shown in Tables 31-33.

[0222] The cefprozil dry suspensions of Examples 30-35 and Comparative Examples 2-7 were tested, and the results are as follows.

[0223] The testing items and requirements are the same as those in Examples 1 to 3.

[0224] The test results are as follows: The particle sizes of Examples 30-35 are all within the acceptable range (0.5-0.71 μm), and the particle sizes of Comparative Examples 2-7 are also within the acceptable range. Examples 30-35 showed no discoloration or agglomeration after 15 days, while Comparative Examples 2-7 showed no discoloration or agglomeration after 0-7 days, but all showed discoloration and agglomeration after 15 days. Dispersion occurred in the resolubility tests of Examples 30-35, while the dispersion effect was poor in Comparative Examples 2-7. The dissolution rate of Examples 30-35 was ≥80% after 15 days, while the dissolution rate of Comparative Examples 2-7 met the standard after 0-7 days, but did not meet the standard after 15 days.

[0225] Results Analysis: The formulation of this invention includes cefprozil, molecular sieve agent, hygroscopic agent, excipient, and suspending agent. The excipient includes surface modifier, carrier, and flavoring agent. The absence of any one of these components has a relatively small impact on the finished granules in the short term, but over time, the overall performance (including hygroscopicity, resolubility, and dissolution rate) decreases significantly, which is detrimental to storage and reduces the efficacy of the medicine. It can be seen that the raw material compatibility of this application is superior.

[0226] In summary, the finished product of this application outperforms commercially available products of the prior art. Further optimization of the preparation conditions yields:

[0227] (1) The optimal weight values ​​are: molecular sieve agent 3 parts, hygroscopic agent 3 parts, surface modifier 2 parts, carrier 2 parts, and suspending agent 3 parts.

[0228] (2) The composition is optimal. Mango cellulose is preferred as the flavoring agent, silica gel is preferred as the hygroscopic agent, and the finished product particles prepared with silicone oil as the surface modifier have smaller particle size, while the finished product particles prepared with polyvinylpyrrolidone have better resolubility.

[0229] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A cefprozil dry suspension, characterized in that, The cefprozil dry suspension comprises the following raw materials: cefprozil, molecular sieve agent, hygroscopic agent, excipient, and suspending agent; the molecular sieve agent is silica; the hygroscopic agent includes at least one of silica gel and silica. The excipient is composed of a surface modifier, a carrier, and a flavoring agent; the flavoring agent includes at least one of mango cellulose, sucrose, glucose, fructose, and lactose, wherein the mango cellulose is cellulose extracted from mango; The carrier is at least one of methylcellulose and sodium carboxymethylcellulose; The surface modifier includes at least one of polyvinylpyrrolidone and silicone oil; The suspending agent includes at least one of methylcellulose, sodium carboxymethylcellulose, cellulose acetate, and polyethylene glycol; The cefprozil dry suspension comprises the following raw materials in parts by weight: 100 parts by weight of cefprozil, 1-5% by weight of hygroscopic agent, 2-5% by weight of silica, and 8-20% by weight of excipients and suspending agents.

2. The cefprozil dry suspension according to claim 1, characterized in that, The cefprozil is 100 parts by weight, the surface modifier is 1-3% by weight of cefprozil, the carrier is 1-2% by weight of cefprozil, and the suspending agent is 1-5% by weight of cefprozil.

3. A method for preparing cefprozil dry suspension according to any one of claims 1 to 2, characterized in that, The cefprozil dry suspension is prepared by spray granulation. First, the molecular sieve agent, cefprozil, carrier, and hygroscopic agent are mixed evenly. Then, the surface modifier, the suspending agent, and the flavoring agent are added and mixed evenly to obtain a mixture. The mixture is then spray-dried and granulated to obtain the cefprozil dry suspension.

4. The method for preparing cefprozil dry suspension according to claim 3, characterized in that, Mixing time is 10-30 minutes.

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