CN115844842A - Doxycycline hydrochloride tablet and preparation method thereof - Google Patents
Doxycycline hydrochloride tablet and preparation method thereof Download PDFInfo
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- CN115844842A CN115844842A CN202211698190.XA CN202211698190A CN115844842A CN 115844842 A CN115844842 A CN 115844842A CN 202211698190 A CN202211698190 A CN 202211698190A CN 115844842 A CN115844842 A CN 115844842A
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- PTNZGHXUZDHMIQ-UHFFFAOYSA-N 4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide;hydrochloride Chemical compound Cl.C1=CC=C2C(C)C(C(O)C3C(C(O)=C(C(N)=O)C(=O)C3N(C)C)(O)C3=O)C3=C(O)C2=C1O PTNZGHXUZDHMIQ-UHFFFAOYSA-N 0.000 title claims abstract description 135
- 229960004082 doxycycline hydrochloride Drugs 0.000 title claims abstract description 135
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 238000003756 stirring Methods 0.000 claims abstract description 71
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 54
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Abstract
The invention discloses a preparation method of doxycycline hydrochloride tablets, which comprises the following steps: adding doxycycline hydrochloride into acetic acid solution, stirring uniformly, adding chitosan, swelling uniformly at 40-60 ℃, and stirring to obtain pre-dispersed doxycycline hydrochloride; adding sodium alginate and collagen into water, and stirring uniformly to obtain a sodium alginate composite solution; adding span-80 into liquid paraffin, stirring, dropwise adding pre-dispersed doxycycline hydrochloride into the mixture under stirring, continuously stirring for 1-2h, adjusting the pH value of the system to 3-4, adding a sodium alginate composite solution, stirring for 10-20min, dropwise adding a glutaraldehyde solution, continuously stirring for 1-2h, washing, and drying to obtain pre-coated doxycycline hydrochloride; adding an adhesive solution into the pre-coated doxycycline hydrochloride, uniformly mixing, then adding lactose, calcium silicate and magnesium stearate, uniformly mixing, granulating, drying, sieving and tabletting to obtain the doxycycline hydrochloride tablet.
Description
Technical Field
The invention relates to the technical field of drug sustained release, in particular to a doxycycline hydrochloride tablet and a preparation method thereof.
Background
Doxycycline hydrochloride belongs to semisynthetic tetracycline broad-spectrum antibiotics, has minimal toxicity in tetracycline antibiotics, has antibacterial activity superior to that of tetracycline, and has an action effect 4 times that of tetracycline. The antibacterial action mechanism of doxycycline hydrochloride is that doxycycline hydrochloride enters thalli, has a specific effect on bacteria and affects multiple links of bacterial protein synthesis. In addition, doxycycline hydrochloride also has the effects of resisting inflammation, tumors, fibrosis, oxidation and blood vessels, can be used for diagnosing malignant tumors of lung, bladder, stomach, oral cavity and other parts, promoting fibrous adhesion, closing cyst cavity, accelerating the healing of body wounds, inhibiting inflammatory cells from producing metalloprotease and the like.
The doxycycline hydrochloride is yellow or light yellow crystalline powder, has no odor, bitter taste, no volatility and no corrosiveness, is easily soluble in methanol and water, has the solubility of about 20g/mL in water, is slightly soluble in ethanol and acetone, and is insoluble in chloroform. The doxycycline hydrochloride aqueous solution is unstable and is easy to have oxidation reaction, and the phenomenon reduces the use effect of doxycycline hydrochloride and seriously influences the clinical use of doxycycline hydrochloride.
The conventional doxycycline hydrochloride dosage forms mainly comprise tablets, injections, powder, capsules and the like which are commonly used in the market, have obvious effect and are widely applied. The doxycycline hydrochloride tablet has the advantages of accurate dosage, convenience in carrying and taking and the like, and is widely popularized and applied.
The preparation of doxycycline hydrochloride tablets generally comprises the steps of crushing and sieving materials, uniformly mixing, granulating, drying and tabletting, and can also be directly pressed into tablets without a granulating link. The conventional doxycycline hydrochloride tablet has the defects of unstable physical property, easy hydrolysis and oxidation when being exposed to light and heat, incapability of being placed for a long time, and influence on clinical application due to overhigh release speed.
Disclosure of Invention
The invention aims to solve the defects in the prior art and provides a doxycycline hydrochloride tablet and a preparation method thereof.
A preparation method of doxycycline hydrochloride tablets comprises the following steps:
(1) Adding doxycycline hydrochloride into acetic acid solution, stirring uniformly, adding chitosan, swelling uniformly at 40-60 ℃, and stirring to obtain pre-dispersed doxycycline hydrochloride;
(2) Adding sodium alginate and collagen into water, and stirring uniformly to obtain a sodium alginate composite solution;
(3) Adding span-80 into liquid paraffin, stirring, dropwise adding pre-dispersed doxycycline hydrochloride into the mixture under stirring, continuously stirring for 1-2h, adjusting the pH value of the system to 3-4, adding a sodium alginate composite solution, stirring for 10-20min, dropwise adding a glutaraldehyde solution, continuously stirring for 1-2h, washing, and drying to obtain pre-coated doxycycline hydrochloride;
(4) Adding an adhesive solution into the pre-coated doxycycline hydrochloride, uniformly mixing, then adding lactose, calcium silicate and magnesium stearate, uniformly mixing, granulating, drying, sieving and tabletting to obtain the doxycycline hydrochloride tablet.
Preferably, in the step (1), the mass ratio of doxycycline hydrochloride to chitosan is 1-5:2-10.
Preferably, in the step (1), the mass fraction of the acetic acid solution is 1-4%.
Preferably, in the step (2), the mass ratio of sodium alginate to collagen is 1-3:1-2.
Preferably, in the step (2), the concentration of the glutaraldehyde solution is 0.1-0.8mol/L, and the mass ratio of span-80, the pre-dispersed doxycycline hydrochloride, the sodium alginate composite solution and the glutaraldehyde solution is 1-3:25-55:7-15:1-3.
Preferably, in step (3), petroleum ether and isopropanol are alternately used for washing.
Preferably, in the step (4), the mass ratio of the pre-coated doxycycline hydrochloride, the adhesive, the lactose, the calcium silicate and the magnesium stearate is 115-195:1-4:1-3:1-2:1-2.
Preferably, in step (4), the dried product is sieved through a 10-mesh sieve.
Preferably, in the step (4), the binder is at least one of starch, sucrose, polyvinyl alcohol and polyethylene glycol.
A doxycycline hydrochloride tablet is prepared by adopting the preparation method of the doxycycline hydrochloride tablet.
The technical effects of the invention are as follows:
the method comprises the steps of dissolving doxycycline hydrochloride in an acetic acid solution, then compounding with chitosan to prepare pre-dispersed doxycycline hydrochloride, dripping the pre-dispersed doxycycline hydrochloride into liquid paraffin containing span-80 to form a water-in-oil system, uniformly dispersing the pre-dispersed doxycycline hydrochloride in the system in a droplet shape, then adjusting the pH value of the system to 3-4, adding a sodium alginate composite solution into the system, wherein the chitosan in the pre-dispersed doxycycline hydrochloride contains amino and is combined with a hydrogen ion to form polyelectrolyte with-NH 3+, the sodium alginate is a polyanion compound with negative charges, and the sodium alginate is adsorbed on the surface of the small droplet of the pre-dispersed doxycycline hydrochloride under the electrostatic action, so that the solubility of the dispersed doxycycline hydrochloride is reduced to cause precipitation. At this time, although doxycycline hydrochloride is embedded therein, the structural stability is poor, and the doxycycline hydrochloride exudation phenomenon is very easy to occur in the subsequent tabletting process.
According to the invention, a glutaraldehyde solution is further added, as the chitosan contains a large amount of hydrophilic hydroxyl and amino, the collagen molecule contains a large amount of amino, and the glutaraldehyde contains two aldehyde groups, the nucleophilic reagent attack is facilitated, so that a layer of polymer network structure is further coated on the surface of doxycycline hydrochloride, doxycycline hydrochloride dissolved in the chitosan solution is coated in the polymer network structure, and meanwhile, as the added collagen has excellent bioactivity and biocompatibility with an organism, the problem of low early-stage drug release speed caused by double coating can be effectively solved.
According to the invention, sodium alginate and chitosan are compounded and combined and coated on the surface of doxycycline hydrochloride, and then glutaraldehyde is adopted for crosslinking and double coating, so that the doxycycline hydrochloride exudation phenomenon in the tabletting process can be effectively avoided, and the problems that the doxycycline hydrochloride is sensitive to humidity and heat and is easy to cause oxidation and degradation of active ingredients are solved. The invention improves the damp-heat stability of doxycycline hydrochloride characters, does not degrade and discolor even under a high-humidity environment, and can be popularized and applied in a large scale.
Drawings
Figure 1 is a graph comparing the cumulative release rate over time of doxycycline hydrochloride tablets from example 5 and comparative examples and doxycycline hydrochloride drug substance in an artificial gastric fluid environment.
Detailed Description
The present invention will be further illustrated with reference to the following specific examples.
Example 1
A preparation method of doxycycline hydrochloride tablets comprises the following steps:
(1) Adding 1kg of doxycycline hydrochloride into 20kg of acetic acid solution with the mass fraction of 1%, uniformly stirring, adding 2kg of chitosan, uniformly swelling at 40 ℃, and stirring at the speed of 500r/min for 10min to obtain pre-dispersed doxycycline hydrochloride;
(2) Adding 1kg of sodium alginate and 1kg of collagen into 5kg of water, and uniformly stirring to obtain a sodium alginate composite solution;
(3) Adding 1kg of span-80 into 80kg of liquid paraffin, stirring at the speed of 100r/min for 10min, dropwise adding 25kg of pre-dispersed doxycycline hydrochloride into the mixture under the stirring state, continuing stirring for 1h, adjusting the pH value of the system to be 3-4 by adopting an acetic acid solution with the mass fraction of 5%, adding 7kg of a sodium alginate composite solution, stirring for 10min, dropwise adding 1kg of a glutaraldehyde solution with the concentration of 0.1mol/L, continuing stirring for 1h, alternately washing by adopting petroleum ether and isopropanol, and drying to obtain pre-coated doxycycline hydrochloride;
(4) Adding an aqueous solution containing 1kg of starch into 115kg of the pre-coated doxycycline hydrochloride, uniformly mixing, then adding 1kg of lactose, 1kg of calcium silicate and 1kg of magnesium stearate, uniformly mixing, granulating, drying, sieving with a 10-mesh sieve, and tabletting to obtain the doxycycline hydrochloride tablet.
Example 2
A preparation method of doxycycline hydrochloride tablets comprises the following steps:
(1) Adding 5kg of doxycycline hydrochloride into 40kg of acetic acid solution with the mass fraction of 4%, uniformly stirring, adding 10kg of chitosan, uniformly swelling at 60 ℃, and stirring at the speed of 1500r/min for 30min to obtain pre-dispersed doxycycline hydrochloride;
(2) Adding 3kg of sodium alginate and 2kg of collagen into 10kg of water, and uniformly stirring to obtain a sodium alginate composite solution;
(3) Adding 3kg of span-80 into 120kg of liquid paraffin, stirring for 30min at the speed of 400r/min, dropwise adding 55kg of pre-dispersed doxycycline hydrochloride into the mixture under the stirring state, continuing stirring for 2h, adjusting the pH value of the system to be 3-4 by adopting an acetic acid solution with the mass fraction of 15%, adding 15kg of a sodium alginate composite solution, stirring for 20min, dropwise adding 3kg of a glutaraldehyde solution with the concentration of 0.8mol/L, continuing stirring for 2h, alternately washing by adopting petroleum ether and isopropanol, and drying to obtain pre-coated doxycycline hydrochloride;
(4) Adding aqueous solution containing 4kg of starch into 195kg of precoated doxycycline hydrochloride, uniformly mixing, then adding 3kg of lactose, 2kg of calcium silicate and 2kg of magnesium stearate, uniformly mixing, granulating, drying, sieving with a 10-mesh sieve, and tabletting to obtain the doxycycline hydrochloride tablet.
Example 3
A preparation method of doxycycline hydrochloride tablets comprises the following steps:
(1) Adding 2kg of doxycycline hydrochloride into 35kg of acetic acid solution with the mass fraction of 2%, uniformly stirring, adding 8kg of chitosan, uniformly swelling at 45 ℃, and stirring at the speed of 1200r/min for 15min to obtain pre-dispersed doxycycline hydrochloride;
(2) Adding 2.5kg of sodium alginate and 1.2kg of collagen into 8kg of water, and uniformly stirring to obtain a sodium alginate composite solution;
(3) Adding 1.5kg of span-80 into 110kg of liquid paraffin, stirring at the speed of 200r/min for 25min, dropwise adding 35kg of pre-dispersed doxycycline hydrochloride into the mixture under the stirring state, continuing stirring for 1.8h, adjusting the pH value of the system to be 3-4 by adopting an acetic acid solution with the mass fraction of 8%, adding 13kg of sodium alginate composite solution, stirring for 12min, dropwise adding 2.5kg of glutaraldehyde solution with the concentration of 0.3mol/L, continuing stirring for 1.8h, alternately washing by adopting petroleum ether and isopropanol, and drying to obtain pre-coated doxycycline hydrochloride;
(4) Adding aqueous solution containing 3kg of starch into 135kg of pre-coated doxycycline hydrochloride, uniformly mixing, then adding 1.5kg of lactose, 1.7kg of calcium silicate and 1.2kg of magnesium stearate, uniformly mixing, granulating, drying, sieving by a 10-mesh sieve, and tabletting to obtain the doxycycline hydrochloride tablet.
Example 4
A preparation method of doxycycline hydrochloride tablets comprises the following steps:
(1) Adding 4kg of doxycycline hydrochloride into 25kg of acetic acid solution with the mass fraction of 3%, uniformly stirring, adding 4kg of chitosan, uniformly swelling at 55 ℃, and stirring at the speed of 800r/min for 25min to obtain pre-dispersed doxycycline hydrochloride;
(2) Adding 1.5kg of sodium alginate and 1.8kg of collagen into 6kg of water, and uniformly stirring to obtain a sodium alginate composite solution;
(3) Adding 2.5kg of span-80 into 90kg of liquid paraffin, stirring for 15min at the speed of 300r/min, dropwise adding 45kg of pre-dispersed doxycycline hydrochloride into the mixture under the stirring state, continuing stirring for 1.2h, adjusting the pH value of a system to be 3-4 by adopting an acetic acid solution with the mass fraction of 12%, adding 9kg of sodium alginate composite solution, stirring for 18min, dropwise adding 1.5kg of glutaraldehyde solution with the concentration of 0.7mol/L, continuing stirring for 1.2h, alternately washing by adopting petroleum ether and isopropanol, and drying to obtain pre-coated doxycycline hydrochloride;
(4) Adding an aqueous solution containing 2kg of starch into 175kg of the pre-coated doxycycline hydrochloride, uniformly mixing, then adding 2.5kg of lactose, 1.3kg of calcium silicate and 1.8kg of magnesium stearate, uniformly mixing, granulating, drying, sieving by a 10-mesh sieve, and tabletting to obtain the doxycycline hydrochloride tablet.
Example 5
A preparation method of doxycycline hydrochloride tablets comprises the following steps:
(1) Adding 3kg of doxycycline hydrochloride into 30kg of acetic acid solution with the mass fraction of 2.5%, uniformly stirring, adding 6kg of chitosan, uniformly swelling at 50 ℃, and stirring at the speed of 1000r/min for 20min to obtain pre-dispersed doxycycline hydrochloride;
(2) Adding 2kg of sodium alginate and 1.5kg of collagen into 7kg of water, and uniformly stirring to obtain a sodium alginate composite solution;
(3) Adding 2kg of span-80 into 100kg of liquid paraffin, stirring for 20min at the speed of 260r/min, dropwise adding 40kg of pre-dispersed doxycycline hydrochloride into the mixture under the stirring state, continuously stirring for 1.5h, adjusting the pH value of the system to be 3-4 by adopting an acetic acid solution with the mass fraction of 10%, adding 11kg of a sodium alginate composite solution, stirring for 15min, dropwise adding 2kg of a glutaraldehyde solution with the concentration of 0.5mol/L, continuously stirring for 1.5h, alternately washing by adopting petroleum ether and isopropanol, and drying to obtain pre-coated doxycycline hydrochloride;
(4) Adding an aqueous solution containing 2.5kg of starch into 155kg of pre-coated doxycycline hydrochloride, uniformly mixing, then adding 2kg of lactose, 1.5kg of calcium silicate and 1.5kg of magnesium stearate, uniformly mixing, granulating, drying, sieving by a 10-mesh sieve, and tabletting to obtain the doxycycline hydrochloride tablet.
Comparative example
A preparation method of doxycycline hydrochloride tablets comprises the following steps:
(1) Adding 3kg of doxycycline hydrochloride into 30kg of acetic acid solution with the mass fraction of 2.5%, uniformly stirring, adding 6kg of chitosan, uniformly swelling at 50 ℃, and stirring at the speed of 1000r/min for 20min to obtain pre-dispersed doxycycline hydrochloride;
(2) Adding 2kg of span-80 into 100kg of liquid paraffin, stirring at the speed of 260r/min for 20min, dropwise adding 40kg of pre-dispersed doxycycline hydrochloride into the mixture under the stirring state, continuing stirring for 1.5h, adjusting the pH value of the system to be 3-4 by adopting an acetic acid solution with the mass fraction of 10%, dropwise adding 2kg of a glutaraldehyde solution with the concentration of 0.5mol/L, continuing stirring for 1.5h, alternately washing by adopting petroleum ether and isopropanol, and drying to obtain pre-coated doxycycline hydrochloride;
(3) Adding an aqueous solution containing 2.5kg of starch into 155kg of pre-coated doxycycline hydrochloride, uniformly mixing, then adding 2kg of lactose, 1.5kg of calcium silicate and 1.5kg of magnesium stearate, uniformly mixing, granulating, drying, sieving by a 10-mesh sieve, and tabletting to obtain the doxycycline hydrochloride tablet.
And (3) performing quality inspection on the doxycycline hydrochloride tablets obtained in the comparative example, observing whether the doxycycline hydrochloride exudation phenomenon occurs, and selecting the doxycycline hydrochloride tablets without exudation phenomenon for subsequent detection.
The doxycycline hydrochloride tablets obtained in example 5 and the comparative example and the release rate of the doxycycline hydrochloride bulk drug are measured by a basket rotating method, which specifically comprises the following steps: the samples were placed in dialysis bags, respectively, and then placed in a drug dissolution apparatus containing 900mL of artificial gastric juice (pH = 1.2) with stirring at 37. + -. 1 ℃ and 100 rm. Sampling 5mL respectively at 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 and 60h, supplementing 5mL of 37 +/-1 ℃ artificial gastric juice into a drug dissolution instrument, filtering the sample, placing 2mL into a 50mL volumetric flask, fixing the volume, shaking up, and calculating the cumulative release rate of doxycycline hydrochloride.
As shown in figure 1, the release rate of doxycycline hydrochloride tablets obtained in example 5 and comparative example was significantly lower than doxycycline hydrochloride drug substance. The cumulative release rate of the doxycycline hydrochloride tablet obtained in the example 5 in the first 12 hours is always higher than that of the comparative example, so that the doxycycline hydrochloride tablet has higher drug concentration in an organism after oral administration and is convenient to absorb and utilize, and then the release rate is reduced in 12-60 hours, so that the cumulative release rate is lower than that of the comparative example, and the long-acting sustained release effect is convenient to maintain.
According to the guideline of drug stability test in the appendix of the second part of the edition of Chinese pharmacopoeia 2005, the stability of the pre-coated doxycycline hydrochloride obtained in example 5 and the comparative example is investigated in high temperature or high humidity environment respectively. Samples were taken at 0d, 5d, and 10d to determine the content, and the appearance properties of the drug powder and microcapsules were observed, compared to that before placement, and the relative percentage content was calculated. Meanwhile, doxycycline hydrochloride bulk drug powder and chitosan are physically mixed to serve as a reference.
I. High temperature test
Placing each group of samples in a culture dish respectively, spreading the samples into a thin layer, placing the thin layer in a stability test box at 60 ℃ for 10 days, sampling the samples respectively on the 5 th day and the 10 th day, observing the appearance of the samples, measuring the content of doxycycline hydrochloride, and calculating the relative content of the doxycycline hydrochloride.
II. High humidity test
Placing each group of samples in a culture dish respectively, spreading the samples into a thin layer, placing the thin layer in a stability test box, placing the samples for 10 days at the temperature of 25 ℃ under the condition that the relative humidity is 90 +/-5%, sampling the samples respectively on the 5 th day and the 10 th day, observing the appearance characters of the samples, measuring the content of doxycycline hydrochloride, and calculating the relative content of the doxycycline hydrochloride.
The above results confirm that: the doxycycline hydrochloride bulk drug has unstable physical properties, is easy to hydrolyze and oxidize when being exposed to light and heat, and cannot be placed for a long time. While example 5 and the comparative example improve the stability of both by providing embedded microcapsules.
However, the high temperature/high humidity stability of example 5 is better than that of the comparative example, because the glutaraldehyde solution is further added, the chitosan contains a large amount of hydrophilic hydroxyl and amino, the collagen molecule contains a large amount of amino, both of which have strong nucleophilicity, and the glutaraldehyde contains two aldehyde groups, which is beneficial to attack of nucleophilic reagents, so that the doxycycline hydrochloride surface is further coated with a layer of polymer network structure, and the doxycycline hydrochloride dissolved in the chitosan solution is crosslinked, thereby effectively forming double coating, and solving the problems that the doxycycline hydrochloride is sensitive to humidity and heat and is easy to cause oxidation and degradation of active ingredients.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and the inventive concepts thereof according to the present invention should be equivalent or changed within the scope of the present invention.
Claims (10)
1. A preparation method of doxycycline hydrochloride tablets is characterized by comprising the following steps:
(1) Adding doxycycline hydrochloride into acetic acid solution, stirring uniformly, adding chitosan, swelling uniformly at 40-60 ℃, and stirring to obtain pre-dispersed doxycycline hydrochloride;
(2) Adding sodium alginate and collagen into water, and uniformly stirring to obtain a sodium alginate composite solution;
(3) Adding span-80 into liquid paraffin, stirring, dropwise adding pre-dispersed doxycycline hydrochloride into the mixture under stirring, continuously stirring for 1-2h, adjusting the pH value of the system to 3-4, adding a sodium alginate composite solution, stirring for 10-20min, dropwise adding a glutaraldehyde solution, continuously stirring for 1-2h, washing, and drying to obtain pre-coated doxycycline hydrochloride;
(4) Adding an adhesive solution into the pre-coated doxycycline hydrochloride, uniformly mixing, then adding lactose, calcium silicate and magnesium stearate, uniformly mixing, granulating, drying, sieving and tabletting to obtain the doxycycline hydrochloride tablet.
2. The preparation method of the doxycycline hydrochloride tablet according to claim 1, wherein in the step (1), the mass ratio of doxycycline hydrochloride to chitosan is 1-5:2-10.
3. The preparation method of doxycycline hydrochloride tablets according to claim 1, wherein in the step (1), the mass fraction of the acetic acid solution is 1-4%.
4. The preparation method of doxycycline hydrochloride tablets according to claim 1, wherein in the step (2), the mass ratio of sodium alginate to collagen is 1-3:1-2.
5. The preparation method of doxycycline hydrochloride tablets according to claim 1, wherein in the step (2), the concentration of the glutaraldehyde solution is 0.1-0.8mol/L, and the mass ratio of span-80, the pre-dispersed doxycycline hydrochloride, the sodium alginate composite solution and the glutaraldehyde solution is 1-3:25-55:7-15:1-3.
6. The method for preparing doxycycline hydrochloride tablet according to claim 1, wherein in the step (3), petroleum ether and isopropanol are alternately washed.
7. The preparation method of doxycycline hydrochloride tablets according to claim 1, wherein in the step (4), the mass ratio of the pre-coated doxycycline hydrochloride, the binder, the lactose, the calcium silicate and the magnesium stearate is 115-195:1-4:1-3:1-2:1-2.
8. The method for preparing doxycycline hydrochloride tablet according to claim 1, wherein in the step (4), the doxycycline hydrochloride tablet is dried and sieved by a 10-mesh sieve.
9. The method for preparing doxycycline hydrochloride tablet according to claim 1, wherein in the step (4), the binder is at least one of starch, sucrose, polyvinyl alcohol and polyethylene glycol.
10. Doxycycline hydrochloride tablets prepared by the method for preparing doxycycline hydrochloride tablets according to any one of claims 1 to 9.
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