CN113750067B - Preparation process of levofloxacin tablets - Google Patents
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Abstract
The invention provides a preparation process of levofloxacin tablets, which comprises the following steps: (1) Respectively pulverizing levofloxacin, microcrystalline cellulose and hydroxypropyl cellulose; (2) Adding talcum powder into ethyl cellulose ethanol solution to prepare coating liquid; (3) Adding the hydroxypropyl cellulose crushed material, the starch nanocrystal and the microcrystalline cellulose crushed material into the levofloxacin crushed material, setting by warm air, granulating, drying, adding magnesium stearate, spraying a coating solution, and tabletting to obtain a tablet core; (4) Preheating the tablet core, and adding the rest coating solution to obtain levofloxacin tablets. The levofloxacin tablet prepared by the invention has the advantages of quality meeting the standard of Chinese pharmacopoeia, good in-vitro dissolution, mild component release rate, favorable improvement of bioavailability, capability of keeping good appearance and moderate hardness of the product under long-term storage, less loss of main drug content, high product quality stability and suitability for industrial large-scale production.
Description
Technical Field
The invention relates to the technical field of pharmaceutical preparation processing, in particular to a preparation process of levofloxacin tablets.
Background
Levofloxacin, chemical name: (S) - (-) -9-fluoro-2, 3-dihydro-3-methyl-10- (4-methyl-1-piperazinyl) -7-oxo-7H-pyrido [1,2,3-de ] - [1,4] benzoxazine-6-carboxylic acid, is a hemihydrate crystal, a quinolone and a levorotatory form of ofloxacin, has about twice the antibacterial activity of ofloxacin, and has a main action mechanism that the activity of bacterial DNA gyrase (bacterial topoisomerase II) is inhibited to inhibit the replication of bacterial DNA so as to achieve the antibacterial effect.
Chinese patent CN112675141A discloses a preparation process of levofloxacin hydrochloride tablets, which comprises stirring, mixing and chopping levofloxacin hydrochloride, pregelatinized starch and carboxymethyl starch sodium, adding 9-10% polyvidone K30 solution, continuously stirring, chopping and sieving to obtain mixed wet granules, drying to obtain mixed dry granules, granulating, adding stearic acid, talcum powder and carboxymethyl starch sodium, totally mixing, tabletting and coating to obtain levofloxacin hydrochloride tablets; chinese patent CN103520124B discloses a preparation method of levofloxacin hydrochloride tablets, wherein levofloxacin hydrochloride and pharmaceutically acceptable auxiliary materials are granulated, dried and sieved to obtain drug-containing granules for later use; dissolving citric acid and polyvinyl acetate phthalate in ethanol, drying to remove ethanol, and sieving to obtain citric acid enteric-coated granule; and uniformly mixing the drug-containing granules, the citric acid enteric-coated granules and the lubricant, and tabletting to obtain the levofloxacin hydrochloride tablets. The prior art solves the problems that levofloxacin is easy to generate sticking phenomenon during tabletting, main drugs and auxiliary materials are mutually bonded and molded, but finished products can generate aggregation phenomenon after long-term storage, the appearance shape of the products is changed, the hardness is reduced, the disintegration is influenced, the stability of the products is poor, and the prior art does not relate to the maintenance of the appearance shape and the hardness of the products.
Disclosure of Invention
Therefore, the invention aims to provide a preparation process of levofloxacin tablets, and solves the problems.
The technical scheme of the invention is realized as follows:
a preparation process of levofloxacin tablets comprises the following preparation steps:
(5) Crushing: taking levofloxacin, grinding, sieving with a sieve with the particle size of 60-70 meshes to obtain a levofloxacin crushed product, taking microcrystalline cellulose, grinding, sieving with a sieve with the particle size of 70-80 meshes to obtain a microcrystalline cellulose crushed product, taking hydroxypropyl cellulose, grinding, and sieving with a sieve with the particle size of 50-60 meshes to obtain a hydroxypropyl cellulose crushed product;
(6) Coating liquid: adding talcum powder into ethyl cellulose ethanol solution, and stirring to obtain coating solution;
(7) A tablet core: adding a hydroxypropyl cellulose crushed substance into the levofloxacin crushed substance, mixing, adding starch nanocrystal and microcrystalline cellulose crushed substance, warm air setting, granulating, drying to obtain a granulated substance, adding magnesium stearate to obtain a mixture, spraying 18-22% of the total weight of the coating liquid formula, and tabletting to obtain a tablet core;
(8) And (3) finished product: preheating the tablet core, adding the rest coating solution, stirring, and drying to obtain levofloxacin tablets.
Further, the levofloxacin tablet comprises the following raw materials in parts by weight: 100 to 120 parts of levofloxacin, 15 to 25 parts of microcrystalline cellulose, 15 to 25 parts of hydroxypropyl cellulose, 10 to 15 parts of starch nanocrystal, 20 to 30 parts of ethyl cellulose ethanol solution, 5 to 10 parts of talcum powder and 5 to 8 parts of magnesium stearate;
further, the preparation method of the ethyl cellulose ethanol solution comprises the following steps: adding ethyl cellulose into an ethanol solution with the mass concentration of 80-85%, and stirring in a water bath at 20-25 ℃ until the ethyl cellulose is dissolved; wherein the dosage ratio of the ethyl cellulose to the ethanol solution with the mass concentration of 80-85% is as follows: (15-20) g: (80-100) mL;
further, the preparation method of the starch nanocrystal comprises the following steps: crushing wheat, adding a sodium hydroxide solution with the mass concentration of 10-12%, immersing for 18-20 h, and centrifuging; taking the precipitate, adding amylase, performing enzymolysis for 10-14 h in a water bath at 35-40 ℃, adding water to adjust the solid content to 60-70%, and adding amylase to perform enzymolysis repeatedly for 2-3 times to obtain an enzymolysis solution; adding hydrochloric acid solution with mass concentration of 20-30%, performing water bath reaction at 35-40 ℃ for 1-2 d, and performing spray drying to obtain the product; the mass ratio of the precipitate to the amylase is 1: 0.02-0.04 percent; the volume ratio of the enzymolysis liquid to a hydrochloric acid solution with the mass concentration of 20-30% is 1:1.5 to 1.8;
further, in the step (3), the warm air is shaped at the temperature of 20-25 ℃ and the air volume of 1800-2200 m 3 H, the time is 25-35 min;
further, the drying is carried out at the temperature of 30-40 ℃ until the moisture content of the granules is 6-8%;
further explaining, in the step (3), the spraying treatment is that the mixture is stirred at the speed of 80-90 r/min while being sprayed, and after the spraying is finished, the mixture is kept stand for 20-30 min;
further explaining, the spraying speed is 8-10 mL/min, and the temperature is 20-25 ℃;
further explaining, in the step (4), the preheating is carried out for 10-12 min at the temperature of 25-30 ℃; stirring is carried out for 40-60 min at the speed of 200-400 r/min.
Compared with the prior art, the invention has the beneficial effects that:
the invention adopts scientific proportioning and optimizes the dosage of main drugs and auxiliary materials, so that the prepared levofloxacin tablet has good dissolution, mild release rate and high bioavailability; under the condition of long-term storage, the appearance shape is kept good, the hardness is moderate and controllable, the loss of the content of the main drug is less, the product stability is high, and the quality is controllable.
In addition, the invention adopts main drugs and auxiliary materials with different particle diameters, and can preliminarily coat the particles of the main drugs and the auxiliary materials by combining the addition of the auxiliary materials and controlling the addition conditions of the coating liquid, thereby increasing the cohesion, plasticity and viscosity of the particles, reducing the elasticity, being beneficial to controlling the hardness of the tablets, avoiding overhigh hardness, ensuring that the tablets are not easy to loosen and improving the appearance; the levofloxacin tablet is added with the starch nanocrystal, and is mixed with the microcrystalline cellulose powder in the tablet core, and the levofloxacin tablet is shaped by warm air, so that the covalent bond connection between the bonding sites on the surface of the starch nanocrystal and the microcrystalline cellulose powder can be enhanced, the viscosity and the expansibility of the levofloxacin tablet can be improved, the main drug and the auxiliary material can easily form a polymer matrix phase, the polymer matrix phase can gradually disintegrate the connecting bonds in a medium, the release rate of the active ingredients of a finished product can be controlled, and the bioavailability can be further improved.
Detailed Description
In order to better understand the technical content of the invention, specific examples are provided below to further illustrate the invention.
The experimental methods used in the examples of the present invention are all conventional methods unless otherwise specified.
The materials, reagents and the like used in the examples of the present invention can be obtained commercially without specific description.
Example 1
The levofloxacin tablet comprises the following raw materials in parts by weight: 100g of levofloxacin, 15g of microcrystalline cellulose, 15g of hydroxypropyl cellulose, 10g of starch nanocrystal, 20g of ethyl cellulose ethanol solution, 5g of talcum powder and 5g of magnesium stearate;
the preparation method of the ethyl cellulose ethanol solution comprises the following steps: according to the dosage ratio of 15g:80mL, adding ethyl cellulose into an ethanol solution with the mass concentration of 80%, and stirring in a water bath at 20 ℃ until the ethyl cellulose is dissolved;
the preparation method of the starch nanocrystal comprises the following steps: crushing wheat, adding a sodium hydroxide solution with the mass concentration of 10%, immersing for 18h, and centrifuging; the mass ratio is 1:0.02, taking the precipitate, adding amylase, performing enzymolysis in a water bath at 35 ℃ for 10 hours, adding water to adjust the solid content to 60%, adding amylase, and performing enzymolysis repeatedly for 2 times to obtain an enzymolysis solution; according to the volume ratio of 1:1.5, adding a hydrochloric acid solution with the mass concentration of 20%, carrying out water bath reaction at 35 ℃ for 1d, and carrying out spray drying to obtain the compound;
the preparation steps of the levofloxacin tablet are as follows:
(1) Crushing: grinding levofloxacin, sieving with a particle size of 60 meshes to obtain a levofloxacin crushed substance, grinding microcrystalline cellulose, sieving with a particle size of 80 meshes to obtain a microcrystalline cellulose crushed substance, grinding hydroxypropyl cellulose, and sieving with a particle size of 60 meshes to obtain a hydroxypropyl cellulose crushed substance;
(2) Coating liquid: adding talcum powder into ethyl cellulose ethanol solution, and stirring to obtain coating solution;
(3) A tablet core: adding hydroxypropyl cellulose powder into the levofloxacin pulverized product, mixing, adding starch nanocrystal and microcrystalline cellulose powder, and shaping with warm air at 20 deg.C and 1800m 3 H, 25min, granulating, drying at 30 ℃ until the water content of the granules is 6 percent to obtain granules, adding magnesium stearate to obtain a mixture, stirring the mixture at the speed of 80r/min, spraying 18 percent of the total weight of the coating liquid while stirring, spraying 8mL/min at the speed of 20 ℃, standing for 20min after spraying, and tabletting to obtain a tablet core;
(4) And (3) finished product: preheating the tablet core at 25 deg.C for 10min, adding the rest coating solution, stirring at 200r/min for 60min, and drying to obtain the final product.
Example 2
The levofloxacin tablet comprises the following raw materials in parts by weight: 120g of levofloxacin, 25g of microcrystalline cellulose, 25g of hydroxypropyl cellulose, 15g of starch nanocrystal, 30g of ethyl cellulose ethanol solution, 10g of talcum powder and 8g of magnesium stearate;
the preparation method of the ethyl cellulose ethanol solution comprises the following steps: according to the dosage ratio of 20g:100mL, adding ethyl cellulose into an ethanol solution with the mass concentration of 85%, and stirring in a water bath at 25 ℃ until the ethyl cellulose is dissolved;
the preparation method of the starch nanocrystal comprises the following steps: crushing wheat, adding a sodium hydroxide solution with the mass concentration of 12%, immersing for 20h, and centrifuging; the mass ratio is 1:0.04, taking the precipitate, adding amylase, performing enzymolysis in water bath at 40 ℃ for 14h, adding water to adjust the solid content to 70%, adding amylase, and performing enzymolysis repeatedly for 3 times to obtain an enzymolysis solution; according to the volume ratio of 1:1.8, adding a hydrochloric acid solution with the mass concentration of 30%, carrying out water bath reaction at 40 ℃ for 2d, and carrying out spray drying to obtain the compound;
the preparation steps of the levofloxacin tablet are as follows:
(1) Crushing: grinding levofloxacin, sieving with a 70-mesh sieve to obtain a levofloxacin crushed product, grinding microcrystalline cellulose, sieving with a 70-mesh sieve to obtain a microcrystalline cellulose crushed product, grinding hydroxypropyl cellulose, and sieving with a 50-mesh sieve to obtain a hydroxypropyl cellulose crushed product;
(2) Coating liquid: adding talcum powder into ethyl cellulose ethanol solution, and stirring to obtain coating solution;
(3) A tablet core: adding hydroxypropyl cellulose powder into the levofloxacin pulverized material, mixing, adding starch nanocrystal and microcrystalline cellulose powder, and shaping with warm air at 25 deg.C and 2200m 3 H, time is 35min, granulation is carried out, drying is carried out at 40 ℃ until the water content of the granules is 8%, granules are obtained, magnesium stearate is added, a mixture is obtained, the mixture is stirred at the speed of 90r/min, 22% of the total weight of the coating liquid is sprayed while stirring, the spraying speed is 10mL/min, the temperature is 25 ℃, after the spraying is finished, standing is carried out for 30min, and tabletting is carried out, so that a tablet core is obtained;
(4) And (3) finished product: preheating the tablet core at 30 deg.C for 12min, adding the rest coating solution, stirring at 400r/min for 40min, and drying to obtain the final product.
Example 3
The levofloxacin tablet comprises the following raw materials in parts by weight: 110g of levofloxacin, 20g of microcrystalline cellulose, 20g of hydroxypropyl cellulose, 12g of starch nanocrystal, 25g of ethyl cellulose ethanol solution, 8g of talcum powder and 6g of magnesium stearate;
the preparation method of the ethyl cellulose ethanol solution comprises the following steps: the dosage ratio is as follows: 18g:90mL, adding ethyl cellulose into an ethanol solution with the mass concentration of 82%, and stirring in a water bath at 22 ℃ until the ethyl cellulose is dissolved;
the preparation method of the starch nanocrystal comprises the following steps: crushing wheat, adding a sodium hydroxide solution with the mass concentration of 11%, immersing for 19 hours, and centrifuging; according to the mass ratio of 1:0.03, taking the precipitate, adding amylase, performing enzymolysis in water bath at 38 ℃ for 12h, adding water to adjust the solid content to 65%, adding amylase, and performing enzymolysis repeatedly for 3 times to obtain an enzymolysis solution; according to the volume ratio of 1:1.6, adding a hydrochloric acid solution with the mass concentration of 25%, carrying out water bath reaction at 38 ℃ for 2d, and carrying out spray drying to obtain the compound;
the preparation steps of the levofloxacin tablet are as follows:
(1) Crushing: grinding levofloxacin, sieving with a 65-mesh sieve to obtain a crushed levofloxacin, grinding microcrystalline cellulose, sieving with a 75-mesh sieve to obtain a crushed microcrystalline cellulose, grinding hydroxypropyl cellulose, and sieving with a 55-mesh sieve to obtain a crushed hydroxypropyl cellulose;
(2) Coating liquid: adding talcum powder into ethyl cellulose ethanol solution, and stirring to obtain coating solution;
(3) A tablet core: adding hydroxypropyl cellulose powder into the levofloxacin pulverized material, mixing, adding starch nanocrystal and microcrystalline cellulose powder, and shaping with warm air at 22 deg.C and 2000m air volume 3 H, granulating for 30min, drying at 35 ℃ until the water content of the granulated substance is 7% to obtain a granulated substance, adding magnesium stearate to obtain a mixture, stirring the mixture at the speed of 85r/min, spraying 20% of the total weight of the coating liquid while stirring at the speed of 9mL/min at the temperature of 22 ℃, standing for 25min after spraying, and tabletting to obtain a tablet core;
(4) And (3) finished product: preheating the tablet core at 28 deg.C for 12min, adding the rest coating solution, stirring at 300r/min for 50min, and drying to obtain the final product.
Example 4
The levofloxacin tablet according to the same formulation as that of example 3 is different in the preparation method of the starch nanocrystal, i.e., rice is selected to replace wheat, crushed, added with a sodium hydroxide solution with a mass concentration of 15% to immerse and soak for 19h, and centrifuged; according to the mass ratio of 1:0.06, taking the precipitate, adding amylase, performing enzymolysis in water bath at 38 ℃ for 12h, adding water to adjust the solid content to 80%, adding amylase, and performing enzymolysis repeatedly for 3 times to obtain an enzymolysis solution; according to the volume ratio of 1:2, adding a hydrochloric acid solution with the mass concentration of 25%, carrying out water bath reaction at 38 ℃ for 2d, and carrying out spray drying to obtain the compound.
Example 5
The same formulation of levofloxacin tablets according to example 3, except that in step (3), the spraying treatment was carried out at a spraying rate of 15mL/min and a temperature of 30 ℃.
Comparative example 1
According to the same formula of the levofloxacin tablet in the embodiment 3, the difference is that the grain sizes in the step (1) are different, and the starch nanocrystals are added and mixed with the hydroxypropyl cellulose crushed material in the step (3), namely, (1) levofloxacin is taken and ground, and passes through a grain size of 80 meshes to obtain the levofloxacin crushed material, microcrystalline cellulose is taken and ground, and passes through a grain size of 50 meshes to obtain the microcrystalline cellulose crushed material, and hydroxypropyl cellulose is taken and ground, and passes through a grain size of 70 meshes to obtain the hydroxypropyl cellulose crushed material;
(3) Adding starch nanocrystal and hydroxypropyl cellulose crushed matter into the levofloxacin crushed matter, mixing, adding microcrystalline cellulose crushed matter, and shaping by warm air; the rest of the procedure was the same as in example 3.
Comparative example 2
According to the same formulation of the levofloxacin tablet of the embodiment 3, the difference is that the step (3) is not shaped by warm air, namely, starch nanocrystal and hydroxypropyl cellulose crushed material are added into the levofloxacin crushed material, the mixture is mixed, microcrystalline cellulose crushed material is added, the mixture is granulated, the mixture is dried at 35 ℃ until the moisture content of the granulated material is 4 percent, the granulated material is obtained, magnesium stearate is added, the mixture is stirred at the speed of 85r/min, 30 percent of the total weight of the coating liquid is sprayed while stirring, the spraying speed is 9mL/min, the temperature is 22 ℃, after the spraying is finished, the mixture is kept stand for 25min, and the tablet core is obtained.
Comparative example 3
The same formulation of levofloxacin tablets according to example 3, with the difference that the preparation steps of levofloxacin tablets were different, no spraying treatment was performed before tabletting, i.e.:
(1) Crushing: grinding levofloxacin, sieving with a particle size of 80 meshes to obtain a crushed levofloxacin, grinding microcrystalline cellulose, sieving with a particle size of 50 meshes to obtain a crushed microcrystalline cellulose, grinding hydroxypropyl cellulose, and sieving with a particle size of 70 meshes to obtain a crushed hydroxypropyl cellulose;
(2) Coating liquid: adding talcum powder into ethyl cellulose ethanol solution, and stirring to obtain coating solution;
(3) A tablet core: adding hydroxypropyl cellulose powder into the levofloxacin pulverized product, mixing, adding starch nanocrystal and microcrystalline cellulose powder, and shaping with warm air at 22 deg.C and air volume of 2000m 3 H, granulating for 30min, drying at 35 deg.C until the water content of the granule is 7% to obtain granule, adding magnesium stearate to obtain mixture, and tabletting to obtain tablet core;
(4) And (3) finished product: preheating the tablet core at 28 deg.C for 10min, adding coating solution, stirring at 200r/min for 40min, and drying to obtain the final product.
Test example 1
According to 'Chinese pharmacopoeia' 2020 edition, the release degree of the levofloxacin tablets prepared in the examples 1 to 5 and the comparative examples 1 to 3 of the invention in distilled water is measured by spectrophotometry, the specification of the levofloxacin tablets is 0.1g, the distilled water is 900mL, and the basket method is adopted for 50 r.min -1 Sampling is carried out at 5min, 15 min, 30min, 45min and 60min, 10mL of sample is taken, the same volume of distilled water with the same temperature is supplemented during sampling, and the test results are shown in the following table 1:
as can be seen from the above table, the levofloxacin tablets prepared in embodiments 1 to 3 of the present invention have an accumulated release rate of more than 98% in 45min, which indicates that the present invention adopts scientifically proportioned components and combines with a specific preparation process to control the release rate of the levofloxacin tablets, so that the release rate of the levofloxacin tablets is accelerated after a period of time, which is beneficial to retaining the effective components of the tablets, and plays a role in quickly killing pathogenic bacteria and preventing germs from generating drug resistance in different ways; example 4, the release rate is relatively slow in the first 30min, and the final release rate only reaches 92.4%, which shows that the starch nanocrystal prepared by the specific process can promote the fusion degree of levofloxacin, hydroxypropyl cellulose and microcrystalline cellulose; example 5 the initial release is higher, and the composition dissolves out faster, controls spraying rate and temperature when adding coating liquid, is favorable to making coating liquid preliminary parcel basic remedy and auxiliary material, improves intermolecular acting force.
The accumulative release rate of the levofloxacin tablet in the comparative example 1 and the comparative example 2 is less than 90% in 60min, which shows that the addition of the starch nanocrystal during the preparation of the tablet core is favorable for improving the stability between the main medicine and the auxiliary material, and the adoption of warm air for shaping is more favorable for improving the viscosity and the expansibility between the main medicine and the auxiliary material, so that the levofloxacin tablet has high in-vitro dissolution, controllable and smooth release rate and improved bioavailability; comparative example 3 the main drug has a larger particle size and does not control the in vitro dissolution.
Test example 2
The levofloxacin tablets prepared in examples 1 to 5 of the present invention and comparative examples 1 to 3 were allowed to stand at 25 ℃ ± 2 ℃ and a relative humidity of 60% ± 10% for 6 months, and the hardness and the content of the main drug of the levofloxacin tablets at the end of 0 month and at the end of 6 months were measured according to the "chinese pharmacopoeia" 2020 edition, and the appearance was observed, with the results as shown in table 2:
as can be seen from the above table, the levofloxacin tablets prepared in embodiments 1 to 3 of the present invention have unchanged appearance after being placed for 3 months, have less decrease in hardness and main drug content, and both meet the standard values specified in the chinese pharmacopoeia, which indicates that the present invention adopts scientific mixture ratio and combines with specific production process, so that the levofloxacin tablets can still maintain good appearance after being placed for a long time, effectively preserve the components of the main drug amount of the tablets, and improve the stability of levofloxacin; example 4 has high hardness and low moldability; example 5 hardness is lower, and the combination of principal drug and adjuvant is poorer, showing that controlling the addition condition of coating liquid is favorable to enhancing the cohesion between principal drug and adjuvant particles, avoiding the aggregation of starch nanocrystal nuclei influenced by temperature, further improving the hardness of the product, and being favorable to product molding and retaining effective components.
The content of the main drug in the comparative example 1 is reduced quickly, and the appearance changes of the comparative examples 2 and 3 are obvious, which shows that the special preparation process is adopted, so that the interaction among the components can be enhanced, and the stability and the quality of the product are improved.
In conclusion, the invention adopts a specific preparation process, so that the obtained levofloxacin tablets have better dissolution, the release rate of the components is mild and controllable, the appearance, the hardness and the content of the main drug of the product meet the quality standard of Chinese pharmacopoeia, the product quality is stable, and the invention is beneficial to industrial production.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (5)
1. The preparation process of the levofloxacin tablets is characterized by comprising the following preparation steps:
(1) Crushing: grinding levofloxacin, sieving with a sieve with a particle size of 60-70 meshes to obtain a crushed levofloxacin, grinding microcrystalline cellulose, sieving with a sieve with a particle size of 70-80 meshes to obtain a crushed microcrystalline cellulose, grinding hydroxypropyl cellulose, and sieving with a sieve with a particle size of 50-60 meshes to obtain a crushed hydroxypropyl cellulose;
(2) Coating liquid: adding talcum powder into ethyl cellulose ethanol solution, and stirring to obtain coating solution;
(3) A tablet core: adding a hydroxypropyl cellulose powder into the levofloxacin crushed material, mixing, adding a starch nanocrystal and a microcrystalline cellulose powder, warm air shaping, granulating, drying to obtain a granulated substance, adding magnesium stearate to obtain a mixture, spraying 18-22% of the total weight of the coating liquid formula, and tabletting to obtain a tablet core;
the warm air setting is carried out at the temperature of 20 to 25 ℃ and the air volume of 1800 to 2200m 3 H, the time is 25 to 35min; the spraying treatment is to stir the mixture at the speed of 80 to 90r/min while spraying, and after the spraying is finished, standing for 20 to 30min;
the spraying speed is 8 to 10mL/min, and the temperature is 20 to 25 ℃;
(4) And (3) finished product: preheating the tablet core, adding the rest coating solution, stirring, and drying to obtain levofloxacin tablets;
the levofloxacin tablet is prepared from the following raw materials in parts by weight: 100 to 120 parts of levofloxacin, 15 to 25 parts of microcrystalline cellulose, 15 to 25 parts of hydroxypropyl cellulose, 10 to 15 parts of starch nanocrystal, 20 to 30 parts of ethyl cellulose ethanol solution, 5 to 10 parts of talcum powder and 5 to 8 parts of magnesium stearate;
the preparation method of the starch nanocrystal comprises the following steps: crushing wheat, adding a sodium hydroxide solution with the mass concentration of 10-12%, immersing for 18-20 h, and centrifuging; taking the precipitate, adding amylase, performing enzymolysis in a water bath at the temperature of 35-40 ℃ for 10-14 h, adding water to adjust the solid content to 60-70%, adding amylase, and performing enzymolysis repeatedly for 2-3 times to obtain an enzymolysis solution; adding hydrochloric acid solution with the mass concentration of 20 to 30%, reacting in water bath at the temperature of 35 to 40 ℃ for 1 to 2d, and performing spray drying to obtain the compound; the mass ratio of the precipitate to the amylase is 1:0.02 to 0.04; the volume ratio of the enzymolysis liquid to hydrochloric acid solution with the mass concentration of 20-30% is 1:1.5 to 1.8.
2. The process for preparing levofloxacin tablets according to claim 1, wherein the ethyl cellulose ethanol solution is prepared by the following steps: adding ethyl cellulose into an ethanol solution with the mass concentration of 80-85%, and stirring in a water bath at 20-25 ℃ until the ethyl cellulose is dissolved; wherein the dosage ratio of the ethyl cellulose to an ethanol solution with the mass concentration of 80-85% is as follows: (15 to 20) g: (80 to 100) mL.
3. The process for preparing levofloxacin tablets according to claim 1, wherein the drying is carried out at 30 to 40 ℃ until the moisture content of the granules is 6 to 8%.
4. The process for preparing levofloxacin tablets according to claim 1, wherein in the step (4), the preheating is carried out at 25 to 30 ℃ for 10 to 12min; the stirring is 200 to 400r/min, and the stirring is 40 to 60min.
5. A levofloxacin tablet prepared by the process for preparing a levofloxacin tablet according to any one of claims 1 to 4.
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| CN105601757A (en) * | 2016-03-22 | 2016-05-25 | 中南林业科技大学 | Preparation method of drug carrier crosslinking-modified rice starch nanocrystals |
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