Taste masking method of cefuroxime axetil medicine

Abstract

The invention relates to the technical field of cefuroxime axetil, in particular to a taste masking method of a cefuroxime axetil medicine. Slowly dropwise adding the lavender plant essential oil into the mixed solution; for patients, especially children and people sensitive to odors, unpleasant odors such as bitter smell and fishy smell of cefuroxime axetil can cause the patients to generate an inimical emotion on medicine taking, so that the patients do not take the medicine on time or refuse to take the medicine, and after the lavender plant essential oil is added into a microcapsule wall material solution, the lavender plant essential oil has pleasant fragrance, so that the lavender plant essential oil has a good effect on preventing and treating diseases. According to the cefuroxime axetil pharmaceutical composition, the unpleasant odor of a medicine can be covered, the medication compliance of a patient is improved, and especially for children and people sensitive to taste, the conflict emotion of the patient to cefuroxime axetil can be reduced; components in the lavender plant essential oil can reduce the surface tension of the micro-capsule wall material solution, so that the micro-capsule wall material solution is easier to spread and attach, and the lavender plant essential oil has anti-inflammatory and soothing effects, so that the use effect of the cefuroxime axetil after production is improved.

Description

Technical Field

[0001] The present invention relates to the technical field of cefuroxime axetil, and specifically relates to a method for masking the taste of cefuroxime axetil drugs. Background Art

[0002] As is well known, many drugs have certain special tastes, such as bitter taste, pungent taste, numb taste, etc.; usually, solid preparations for whole swallowing are made for these drugs with unacceptable tastes, such as coated tablets, capsules, etc.; however, the preparations for whole swallowing are not suitable for children or patients with difficulty in swallowing, and suspensions that can be dissolved in water or dispersed into fine particles must be used, such as soluble tablets, granules, solutions or suspensions.

[0003] However, since the drugs in this dosage form are exposed, they inevitably come into direct contact with the taste buds on the oral cavity when taken, so the special taste or bitter taste of the drugs is often felt when taken; Especially cephalosporin drugs, such as cefuroxime axetil, cefuroxime axetil is a β-lactam antibiotic; it appears as a white or off-white powder, almost odorless, bitter in taste; slightly soluble in methanol and absolute ethanol, almost insoluble in water; cefuroxime axetil is applicable to adults with acute pharyngitis or tonsillitis, acute otitis media, maxillary sinusitis, acute exacerbation of chronic bronchitis, acute bronchitis, simple urinary tract infection, skin and soft tissue infection and uncomplicated Neisseria gonorrhoeae urethritis and cervicitis caused by sensitive strains of hemolytic streptococcus, Staphylococcus aureus (except methicillin-resistant strains), Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and other Enterobacteriaceae bacteria; pharyngitis or tonsillitis, acute otitis media, etc. in children; cefuroxime axetil has an extremely bitter taste, especially for children's medications, and the taste masking effects of existing dosage forms are not ideal.

[0004] In summary, to solve the technical problems proposed in this article, the present invention proposes a method for masking the taste of cefuroxime axetil drugs. Summary of the Invention

[0005] The present invention proposes a method for masking the taste of cefuroxime axetil drugs, and this method includes the following steps; S1: Select ethylcellulose and povidone as the microcapsule wall materials, add ethylcellulose and povidone to an organic solvent according to a mass ratio of 3:1. The organic solvent is a mixed solution of ethanol and acetone, and the mass ratio of ethanol to acetone is 2:1. Stir at a temperature of 40°C until completely dissolved to form a uniform microcapsule wall material solution; S2: Add cefuroxime axetil raw material drug to an aqueous solution containing a surfactant. The surfactant is Tween-80, and its mass in the aqueous solution is 1%. Stir evenly to form a cefuroxime axetil suspension; S3: Under stirring conditions, slowly drop the cefuroxime axetil suspension into the microcapsule wall material solution. The mass ratio of cefuroxime axetil to the microcapsule wall material is 1:2. After the dropping is completed, continue stirring for 30 minutes, then add n-hexane to solidify the microcapsules, filter and wash to obtain cefuroxime axetil microcapsules; S4: Dissolve hydroxypropyl methylcellulose and propylene glycol in water according to a mass ratio of 5:1 to prepare a hydrophobic layer; place the cefuroxime axetil microcapsules in a pot and spray the hydrophobic layer evenly on the surface of the microcapsules by means of spraying; the weight gain of the hydrophobic layer is 10%, and after drying, a taste-masked cefuroxime axetil preparation is obtained.

[0006] As a preferred embodiment in the present application, in the above S1 step, ethyl cellulose and polyvinylpyrrolidone are mixed with an organic solvent to form a microcapsule wall material solution, and plant essential oil is added to the microcapsule wall material solution.

[0007] As a preferred embodiment in the present application, the plant essential oil is lavender essential oil, and before adding the lavender essential oil, the lavender essential oil is filtered using a microporous filter membrane.

[0008] As a preferred embodiment in the present application, before adding the lavender essential oil to the microcapsule wall material solution, a natural fragrance compound is added to the lavender essential oil.

[0009] As a preferred embodiment in the present application, the natural fragrance compound is eugenol.

[0010] As a preferred embodiment in the present application, after the above hydroxypropyl methylcellulose and propylene glycol are mixed to form a hydrophobic layer, stearic acid is added to the hydrophobic layer.

[0011] As a preferred embodiment in the present application, in the above S4 step, before the hydrophobic layer is sprayed on the surface of the cefuroxime axetil microcapsules, a disintegrant is added to the surface of the cefuroxime axetil. When the disintegrant is added to the surface of the cefuroxime axetil microcapsules, a filler is added to the disintegrant. After the filler and the disintegrant are mixed, the mixture is added to the surface of the cefuroxime axetil microcapsules.

[0012] As a preferred embodiment in the present application, the disintegrant is selected as sodium carboxymethyl starch, and the filler is selected as lactose.

[0013] The beneficial effects of the present invention are as follows: Slowly drip lavender plant essential oil into the mixed solution; the stirring speed should not be too fast to avoid generating excessive foam; for patients, especially children and those sensitive to odors, the unpleasant odors such as the bitter and fishy smell of cefuroxime axetil will cause patients to be resistant to taking medicine, resulting in non-compliance with taking medicine on time or refusal to take medicine. After the lavender plant essential oil is added to the microcapsule wall material solution, the lavender plant essential oil has a pleasant aroma, which can cover up the bad smell of the drug and improve the medication compliance of patients. Especially for children and those sensitive to taste, it can reduce the resistance of patients to cefuroxime axetil; and the components in the lavender plant essential oil will reduce the surface tension of the microcapsule wall material solution, making the microcapsule wall material solution easier to spread and adhere. Moreover, the lavender plant essential oil itself has anti-inflammatory and soothing effects, thereby improving the use effect of cefuroxime axetil after production. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 is the flowchart of the method in the present invention; DETAILED DESCRIPTION OF THE INVENTION

[0015] In order to make the technical means, creative features, achieved purposes and effects of the present invention easy to understand, the present invention will be further described below in conjunction with specific embodiments.

[0016] Example 1: A method for masking the taste of cefuroxime axetil drug, the method comprising the following steps; S1: Select ethylcellulose and polyvinylpyrrolidone as the microcapsule wall material, add ethylcellulose and polyvinylpyrrolidone to an organic solvent according to a mass ratio of 3:1. The organic solvent is a mixed solution of ethanol and acetone, and the mass ratio of ethanol to acetone is 2:1. Stir at 40 °C until completely dissolved to form a uniform microcapsule wall material solution; S2: Add cefuroxime axetil raw material to an aqueous solution containing a surfactant. The surfactant is Tween-80, and its mass in the aqueous solution is 1%. Stir evenly to form a cefuroxime axetil suspension; S3: Under stirring conditions, slowly drip the cefuroxime axetil suspension into the microcapsule wall material solution. The mass ratio of cefuroxime axetil to the microcapsule wall material is 1:2. After dripping, continue to stir for 30 minutes, then add n-hexane to solidify the microcapsules, filter and wash to obtain cefuroxime axetil microcapsules; S4: Dissolve hydroxypropyl methylcellulose and propylene glycol in water according to a mass ratio of 5:1 to prepare a hydrophobic layer; place the cefuroxime axetil microcapsules in a pot, and spray the hydrophobic layer evenly on the surface of the microcapsules by spraying; the weight gain of the hydrophobic layer is 10%, and the masked cefuroxime axetil preparation is obtained after drying; In the above step S1, after ethyl cellulose and povidone are mixed with an organic solvent, a microcapsule wall material solution is formed, and essential oil of plants is added to the microcapsule wall material solution; The essential oil of plants is lavender essential oil, and before adding the lavender essential oil, the lavender essential oil is filtered using a microporous filter membrane; The principle is as follows; First, ethyl cellulose is added to the mixed solution; the mixed solution is a mixed solution of ethanol and acetone. Ethyl cellulose is a hydrophobic cellulose ether and has good solubility in the mixed solvent of ethanol and acetone. Under the condition that the stirring temperature is 40 °C, ethyl cellulose will gradually disperse and dissolve in the mixed solvent of ethanol and acetone to form a uniform colloidal solution, and the solution will show a certain viscosity; then povidone is added to the solution containing ethyl cellulose; povidone is a water-soluble polymer and can also dissolve well in the mixed solvent of ethanol and acetone; with the addition of povidone, the viscosity of the solution may further increase, and finally a uniform, clear or slightly opalescent microcapsule wall material solution is formed; And when preparing the microcapsule wall material solution, essential oil of natural plants is added to the microcapsule wall solution. The essential oil of natural plants is selected as natural lavender essential oil, and before adding the lavender essential oil, the lavender essential oil is filtered using a microporous filter membrane to filter out the impurities in the lavender essential oil; the lavender essential oil is added to the microcapsule wall material solution, and then the lavender essential oil is stirred to make the lavender essential oil uniformly mixed in the microcapsule wall material solution. When adding the lavender essential oil, the lavender essential oil is slowly dropped into the mixed solution; the stirring speed should not be too fast to avoid generating too many bubbles; for patients, especially children and people sensitive to odors, unpleasant odors such as the bitter and fishy smell of cefuroxime axetil will make patients resistant to taking medicine, resulting in not taking medicine on time or refusing to take medicine. After the lavender essential oil is added to the microcapsule wall material solution, the lavender essential oil has a pleasant aroma, which can cover up the bad smell of the medicine and improve the medication compliance of patients. Especially for children and people sensitive to tastes, it can reduce the resistance of patients to cefuroxime axetil; and the components in the lavender essential oil will reduce the surface tension of the microcapsule wall material solution, making the microcapsule wall material solution easier to spread and adhere, and the lavender essential oil itself has anti-inflammatory and soothing effects, thereby improving the use effect of cefuroxime axetil after production; Cefuroxime axetil is a lipophilic drug with low solubility in water; Tween-80 is a non-ionic surfactant with a hydrophilic group and a hydrophobic group; its hydrophobic group can interact with cefuroxime axetil molecules, and the hydrophilic group interacts with water molecules, thereby reducing the surface tension at the oil-water interface, enabling cefuroxime axetil to be better dispersed in the aqueous solution and increasing its apparent solubility; the surfactant can prevent the aggregation between cefuroxime axetil drug particles, making the cefuroxime axetil raw material evenly dispersed in the aqueous solution, forming a relatively stable suspension and emulsion, which is beneficial to the subsequent formulation process and ensures the uniformity of the drug content in the drug preparation; Specifically, accurately weigh the required Tween-80, add it to an appropriate amount of water at a ratio of 1% by mass, and stir to completely dissolve Tween-80 to form a clear and transparent surfactant aqueous solution; slowly add the cefuroxime axetil raw material to the clear and transparent surfactant aqueous solution, and at the same time turn on the stirring device for stirring; in the initial stage of stirring, the cefuroxime axetil raw material is dispersed in the solution in the form of particles. As the stirring progresses, the particles gradually become smaller, and the turbidity of the solution may increase, but the overall will become more uniform; with continuous stirring, cefuroxime axetil will be evenly dispersed in the solution in the form of fine particles or molecular state, forming a cefuroxime axetil suspension; Subsequently, add the cefuroxime axetil suspension to the microcapsule wall material solution, and make the ratio of the cefuroxime axetil suspension to the microcapsule wall material solution 1:2; after adding the cefuroxime axetil suspension, stir the mixed microcapsule wall material solution for 30 minutes. After stirring, add n-hexane to the microcapsules. As n-hexane is added, due to the polymer starting to precipitate from the solution to form microcapsules; the mixed solution will gradually become turbid. After continuing to stir for a period of time, fine particulate matter will appear, and then microcapsules will be formed; then the microcapsules will precipitate, and after precipitation, the microcapsules will be filtered out by filtration to form cefuroxime axetil microcapsules; Subsequently, accurately weigh hydroxypropyl methylcellulose and propylene glycol in a ratio of 5:1; for example, weigh 5 grams of hydroxypropyl methylcellulose and 1 gram of propylene glycol; add water to a container, turn on the stirring device, and stir evenly; then slowly sprinkle the hydroxypropyl methylcellulose into the water to avoid forming lumps; since hydroxypropyl methylcellulose has a certain viscosity, rapid addition may cause the formation of micelles that are difficult to disperse locally; after the initial dispersion of hydroxypropyl methylcellulose, add the weighed propylene glycol to the solution and continue stirring; propylene glycol can reduce the surface tension of the solution, which helps the better dissolution of hydroxypropyl methylcellulose, and at the same time it can also form a stable hydrophobic layer solution with water and hydroxypropyl methylcellulose. After the solution is formed, place the cefuroxime axetil microcapsules in a clean pot, and then use the spraying method to evenly spray the hydrophobic layer solution on the surface of the cefuroxime axetil microcapsules, so as to form a hydrophobic layer on the surface of the cefuroxime axetil microcapsules, and the hydrophobic layer hydrophobizes the internal cefuroxime axetil; when the patient takes the formed cefuroxime axetil orally, due to the hydrophobic effect of the outer hydrophobic layer, when the patient takes cefuroxime axetil with water, it makes cefuroxime axetil easier to enter the body with water, thereby improving the taking effect of cefuroxime axetil.

[0017] Example Two: Before adding lavender plant essential oil to the microcapsule wall material solution, add a natural fragrance compound to the lavender plant essential oil; The natural fragrance compound is eugenol; The principle is as follows; On the basis of the above example, before adding lavender plant essential oil to the microcapsule wall material solution, add a natural fragrance compound to the lavender plant essential oil. The natural fragrance compound is selected as eugenol. First, weigh eugenol and add eugenol to the microcapsule wall material solution after mixing lavender plant essential oil. During the addition process, slowly drip eugenol into the mixed solution and stir the solution evenly. During the process, ensure that eugenol can be quickly dispersed and avoid generating too many bubbles. After the addition of eugenol is completed, continue stirring for 20 - 40 minutes to make eugenol fully mixed and evenly dispersed with the mixed solution; so that the microcapsule wall material solution contains eugenol and lavender plant essential oil. Eugenol has a unique clove aroma, which matches well with the pleasant floral fragrance of lavender essential oil, making the fragrance of the microcapsule wall material solution more suitable; reducing the resistance of children and patients with sensitive taste; and both eugenol and lavender essential oil have certain biological activities, such as antibacterial and anti-inflammatory effects; the synergistic effect of the two can enhance the antibacterial and anti-inflammatory effects of the microcapsule wall material solution, thereby improving the effect of the formed cefuroxime axetil.

[0018] Example Three: After forming a hydrophobic layer by mixing the above hydroxypropyl methylcellulose and propylene glycol, add stearic acid to the hydrophobic layer; The principle is as follows; On the basis of the above embodiments, stearic acid is added to the hydrophobic layer; an appropriate amount of stearic acid is prepared and heated to melt it so as to better mix with hydroxypropyl methylcellulose and propylene glycol. The melted stearic acid is slowly dropped into the mixture of hydroxypropyl methylcellulose and propylene glycol, and then stirred evenly to avoid generating too many foams and ensure that stearic acid can be evenly dispersed in the mixture. After adding stearic acid, continue to stir for a period of time to fully mix stearic acid with the mixture; after mixing, spray the hydrophobic layer mixed with stearic acid onto the cefuroxime axetil microcapsules; When the hydrophobic layer containing stearic acid is sprayed onto the cefuroxime axetil microcapsules, stearic acid can form a barrier structure in the patient's body to slow down the release rate of the drug from the preparation; stearic acid can act synergistically with hydroxypropyl methylcellulose to regulate the release rate of the drug. As a result, when the patient takes cefuroxime axetil orally with water, stearic acid will reduce the release rate of the drug, thereby reducing the probability of the cefuroxime axetil raw material being released in the mouth, avoiding the taste of cefuroxime axetil in the patient's mouth, and improving the smoothness when the patient takes cefuroxime axetil orally.

[0019] Example 4: In the above step S4, before spraying the hydrophobic layer on the surface of the cefuroxime axetil microcapsules, a disintegrant is added to the surface of the cefuroxime axetil. When the disintegrant is added to the surface of the cefuroxime axetil microcapsules, a filler is added to the disintegrant. After the filler and the disintegrant are mixed, the mixture is added to the surface of the cefuroxime axetil microcapsules; The disintegrant is selected as sodium carboxymethyl starch, and the filler is selected as lactose; The principle is as follows; On the basis of the above embodiments, before spraying the hydrophobic layer on the surface of the cefuroxime axetil microcapsules, a disintegrant is added to the surface of the cefuroxime axetil microcapsules. The disintegrant is selected as sodium carboxymethyl starch, and a filler is added to the disintegrant. The filler is selected as lactose. After the disintegrant and lactose are added to the surface of the cefuroxime axetil microcapsules, the hydrophobic layer is then used to wrap the disintegrant and lactose. On the one hand, the hydrophobic layer prevents the cefuroxime axetil from releasing its efficacy in the mouth. When the patient takes the cefuroxime axetil into the body, the hydrophobic layer dissolves. After the hydrophobic layer dissolves, the disintegrant and lactose absorb moisture in the body and expand in volume, so that the cefuroxime axetil quickly disintegrates, promoting the cefuroxime axetil to be released as soon as possible, improving the dissolution rate and bioavailability of the drug; and by using lactose as a filler, the cefuroxime axetil is protected from external environmental factors such as humidity and oxygen, improving the stability of cefuroxime axetil during storage.

Claims

1. A taste-masking method for a cefuroxime axetil drug, characterized in that: The method comprises the following steps: S1: Ethyl cellulose and polyvinylpyrrolidone are selected as microcapsule wall materials, and ethyl cellulose and polyvinylpyrrolidone are added into an organic solvent at a mass ratio of 3:

1. The organic solvent is a mixed solution of ethanol and acetone, and the mass ratio of ethanol to acetone is 2:

1. Stirring at a temperature of 40°C until completely dissolved to form a uniform microcapsule wall material solution; S2: adding the cefuroxime axetil API to an aqueous solution containing a surfactant, wherein the surfactant is Tween-80, and the mass of the surfactant in the aqueous solution is 1%, and stirring evenly to form a cefuroxime axetil suspension; S3: under stirring conditions, slowly drop the cefuroxime axetil suspension into the microcapsule wall material solution, the mass ratio of cefuroxime axetil to the microcapsule wall material being 1:2, stirring is continued for 30 minutes after the dropwise addition is completed, and then n-hexane is added to solidify the microcapsules, and the microcapsules are filtered and washed to obtain cefuroxime axetil microcapsules; S4: dissolving hydroxypropyl methylcellulose and propylene glycol in water at a mass ratio of 5:1 to prepare a hydrophobic layer; placing cefuroxime axetil microcapsules in a pot, and spraying the hydrophobic layer evenly on the surface of the microcapsules by spraying; the hydrophobic layer has a weight gain of 10%, and after drying, a taste-masked cefuroxime axetil preparation is obtained; Adding plant essential oil to the microcapsule wall material solution formed in S1; The plant essential oil is lavender plant essential oil, and before adding the lavender plant essential oil, the lavender plant essential oil is filtered using a microporous filter membrane.

2. The method for masking the taste of cefuroxime axetil according to claim 1, characterized in that: Before adding the lavender essential oil to the microcapsule wall material solution, natural fragrance compounds are added to the lavender essential oil.

3. The method for masking the taste of cefuroxime axetil according to claim 2, characterized in that: The natural flavor compound is eugenol.

4. The method for masking the taste of cefuroxime axetil according to claim 3, characterized in that: After the hydroxypropyl methylcellulose and propylene glycol are mixed, a hydrophobic layer is formed, and stearic acid is added to the hydrophobic layer.

5. The method for masking the taste of cefuroxime axetil according to claim 1, characterized in that: In the above step S4, before the hydrophobic layer is sprayed on the surface of the cefuroxime axetil microcapsules, a disintegrant is added to the surface of the cefuroxime axetil microcapsules, when the disintegrant is added to the surface of the cefuroxime axetil microcapsules, a filler is added to the disintegrant, and after the filler and the disintegrant are mixed, the mixture is added to the surface of the cefuroxime axetil microcapsules.

6. The method for masking the taste of cefuroxime axetil according to claim 5, characterized in that: The disintegrant is sodium carboxymethyl starch and the filler is lactose.

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