Dihydroxynaphthoic acid pyraclozine praziquantel tablet and preparation method thereof

Abstract

The invention relates to the field of medicine preparation, in particular to a pamoxamic acid pyraclozine praziquantel tablet and a preparation method thereof. The pyrantel pamoate praziquantel tablet is prepared from the following components in parts by weight: 230 parts of pyrantel pamoate, 20 parts of praziquantel, 75 parts of a filling agent, 2 to 5 parts of polyvinylpolypyrrolidone, 3 to 4 parts of magnesium stearate and 7 to 11 parts of a coating material, the filling agent is prepared from 20 to 55 parts of microcrystalline cellulose and 20 to 55 parts of corn starch. According to the application, the polyvinylpolypyrrolidone swells when encountering water, so that the pyrantel pamoate praziquantel tablet is quickly disintegrated into fine particles within a short time, and the dissolution level of the pyrantel pamoate and the praziquantel is improved; the microcrystalline cellulose and the corn starch can be matched with each other, so that the water absorption expansion rate is further increased, and the disintegration effect of the polyvinylpolypyrrolidone is promoted.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of medicine preparation, in particular to a pyrantel pamoate praziquantel tablet and a preparation method thereof. BACKGROUND

[0002] Pyrantel pamoate is a synthetic broad-spectrum, high-efficiency tetrahydropyrimidine nicotinic receptor agonist anthelmintic drug, in which pyrantel as an active ingredient plays its anthelmintic effect. Pyrantel is often used for treating gastrointestinal nematode disease, and has high activity against roundworms, hookworms and pinworms. Praziquantel is an isoquinoline pyrazine derivative, and is an extremely effective anti-trematode and anti-cercaria drug. The two kinds of antiparasitic drugs have significant anthelmintic effect and low toxicity and side effects, and the emphasis and mechanism of anthelmintic are different, and the preparation of a compound tablet helps to expand the anthelmintic range. The two drugs are released rapidly in the gastrointestinal tract to play their anthelmintic effect through oral administration, and the content and dissolution level of the preparation affect the final curative effect. However, in the BCS classification of drugs, pyrantel pamoate and praziquantel are both low-solubility drugs, and the disintegration and release of the preparation and the poor solubility of the drug become the limiting factors of drug dissolution.

[0003] According to the existing preparation procedure, the pre-treatment method of screening mixing will cause static electricity of praziquantel, and due to the small proportion of the prescription, the drug cannot be uniformly dispersed, resulting in uneven content. At the same time, the dissolution rate and dissolution level of the two kinds of raw materials are not synchronized, pyrantel pamoate is hardly absorbed in the gastrointestinal tract, and its dissolution speed is slower and the dissolution level is lower than that of praziquantel, and its poor solubility is the main factor limiting the dissolution of pyrantel pamoate. In order to increase the in-vivo dissolution of the drug, the recommended dosage is usually increased to achieve the purpose of treatment, which increases the risk of adverse reactions. SUMMARY

[0004] In order to solve the problem that the in-vivo dissolution of the drug is increased by increasing the recommended dosage, which easily causes adverse reactions, the present application provides a pyrantel pamoate praziquantel tablet, which is rapidly disintegrated into fine particles in a short time by the swelling of cross-linked povidone in water, so as to improve the dissolution level of pyrantel pamoate and praziquantel; microcrystalline cellulose and corn starch can cooperate with each other to further improve the water absorption swelling rate and promote the disintegration effect of cross-linked povidone.

[0005] In the first aspect, the present application provides a pyrantel pamoate praziquantel tablet, which adopts the following technical solution: A pyrantel pamoate praziquantel tablet comprises the following components by weight: pyrantel pamoate 230 parts, praziquantel 20 parts, filler 75 parts, cross-linked povidone 2-5 parts, magnesium stearate 3-4 parts, and coating material 7-11 parts; the filler comprises microcrystalline cellulose 20-55 parts and corn starch 20-55 parts.

[0006] By adopting the technical scheme, the cross-linked povidone can swell rapidly after meeting water, and generate super strong capillary force, so that the pyrantel pamoate tablet is rapidly disintegrated into fine particles in a short time, the contact area of the drug and the body fluid is greatly increased, and the dissolution levels of the pyrantel pamoate and the pyrantel are improved. The pyrantel pamoate is almost insoluble in water, and the pyrantel is a fat-soluble drug (low solubility in water). The cross-linked povidone improves the dispersibility by physical disintegration, and makes up for the defect of low solubility.

[0007] The microcrystalline cellulose can effectively adsorb the pyrantel particles, and prevent the pyrantel particles from appearing segregation. The microcrystalline cellulose can also improve the compressibility of the particles, and form a porous network. The porous structure can accelerate water penetration when meeting water, and assist the water absorption and swelling of the cross-linked povidone. The corn starch can occupy the gaps between the particles when mixed, buffer the density difference between the substances, and improve the flowability. When the corn starch is used in combination with the microcrystalline cellulose, the water absorption and swelling rate can be further increased, the porosity of the tablet can be adjusted, and the disintegration effect of the cross-linked povidone can be promoted.

[0008] The pyrantel pamoate tablet is rapidly disintegrated into fine particles in a short time by the water swelling of the cross-linked povidone, the dissolution levels of the pyrantel pamoate and the pyrantel are improved, the microcrystalline cellulose and the corn starch can cooperate with each other, the water absorption and swelling rate is further improved, and the disintegration effect of the cross-linked povidone is promoted.

[0009] Preferably, the particle size of the pyrantel is D90≤50 μm.

[0010] By adopting the technical scheme, the proportion of the pyrantel is low, the reduction of the particle size can significantly increase the number of particles, and the spatial distribution density is greatly improved. The surface of the microcrystalline cellulose is rough and porous, the small particle size pyrantel can be embedded in the pores of the microcrystalline cellulose by the mechanical anchoring effect, and the separation tendency is reduced.

[0011] The reduction of the particle size of the pyrantel can expand the dissolution interface, increase the contact probability with the solvent, and overcome the low solubility obstacle. When the cross-linked povidone absorbs water and disintegrates, the small particle size pyrantel can be embedded in the flocculent aggregates, and directly exposed to the solvent.

[0012] Preferably, the mass ratio of the microcrystalline cellulose to the corn starch is 1:0.8-2.

[0013] By adopting the technical scheme, when the content of the corn starch is too low, the particle size gradient is destroyed, the porosity between the particles is increased, the pyrantel particles are prone to migration and stratification, the dispersion effect of the corn starch is lacking, the pyrantel and the pyrantel particles are prone to re-aggregation after disintegration, and the dissolution level is reduced; the content of the corn starch is insufficient, the overall adhesion effect is insufficient, the edges of the tablets are prone to wear, and the stability is reduced. When the content of corn starch is too high, the excess starch forms a continuous phase, and the piperquinoxyI is easily physically isolated, which easily causes the uniformity to decrease; the excessive corn starch absorbs water to easily form a high-viscosity gel layer, which blocks the drug diffusion; therefore, the applicant finally determines that the mass ratio of the microcrystalline cellulose to the corn starch is preferably the above.

[0014] Preferably, the mass ratio of the cross-linked povidone to the magnesium stearate is 4:2-4.

[0015] By adopting the above technical scheme, when the content of magnesium stearate is too low, the inter-particle friction force rises during shearing, the drug particles are broken and migrate, and the uniformity decreases; the insufficient lubrication of the cross-linked povidone absorbs excessive water to form a dense gel barrier, which reduces the dissolution level; when the content of magnesium stearate is too high, the excess magnesium ions neutralize the negative charge of the cross-linked povidone, the cross-linked povidone loses the electrostatic repulsion, and is easily formed into a large particle size lump; the cross-linked povidone is wrapped by the magnesium stearate, the water absorption swelling space is lost, and the disintegration effect is reduced, thereby reducing the dissolution level of the medicament; therefore, the applicant finally determines that the mass ratio of the cross-linked povidone to the magnesium stearate is preferably the above after a large amount of research and experimental verification.

[0016] Preferably, the piperquinoxyI and pyrantel embonate tablet further comprises copovidone.

[0017] By adopting the above technical scheme, the copovidone can wrap the piperquinoxyI fine powder into pseudo-particles, eliminate the electrostatic migration, and reduce the possibility of piperquinoxyI drug segregation. The copovidone is dissolved to form micropores when meeting water, accelerates the penetration of the medium to the tablet core, and is helpful to the water absorption and disintegration of the cross-linked povidone.

[0018] Preferably, the mass ratio of the cross-linked povidone to the copovidone is 1:1-2.

[0019] By adopting the above technical scheme, when the content of copovidone is too low, the promotion effect on the tablet is not good; when the content of copovidone is too high, the cross-linked povidone is trapped by the high-viscosity solution, the swelling rate is reduced, and the dissolution level is reduced; therefore, the applicant finally determines that the mass ratio of the cross-linked povidone to the copovidone is preferably the above after a large amount of research and experimental verification.

[0020] Preferably, the piperquinoxyI and pyrantel embonate tablet further comprises polyvinyl pyrrolidone.

[0021] By adopting the above technical scheme, the polyvinylpyrrolidone can directly wet the pyrantel and other substances to form a drug complex, and can eliminate static electricity and reduce the possibility of component segregation. When encountering water, it can quickly dissolve to establish a hydrophilic microporous network and improve the medium permeation rate. At the same time, it can maintain the opening of the pores to prevent the blocking of the cross-linked povidone water absorption channel and promote disintegration. The polyvinylpyrrolidone can form a hydrogen bond with the amine group of pyrantel to improve the hydrolysis energy barrier. At the same time, it can form a glassy film to reduce oxygen permeation, thereby maintaining the stability of the whole drug.

[0022] Preferably, the weight of the polyvinylpyrrolidone is 50-85 parts.

[0023] By adopting the above technical scheme, when the content of polyvinylpyrrolidone is too low, the promotion effect on the tablet is not good; when the content of polyvinylpyrrolidone is too high, a continuous film is easily formed, and the fluidity between components decreases; after water absorption, a high-viscosity gel layer is formed, the diffusion coefficient decreases, and the cross-linked povidone swells after water absorption and is imprisoned by the gel layer, resulting in difficulty in disintegration and reducing the dissolution level; during storage, it is easy to absorb moisture in the air and be imprisoned in the tablet, accelerating hydrolysis; therefore, after a large amount of research and experimental verification, the applicant finally determines that the weight of the polyvinylpyrrolidone in the present application is preferably as described above.

[0024] In a second aspect, the present application provides a preparation method of praziquantel pyrantel pamoate tablets, which adopts the following technical scheme: A preparation method of praziquantel pyrantel pamoate tablets for preparing the above-mentioned praziquantel pyrantel pamoate tablets, comprising the following steps: Primary mixing: mixing the formula amount of microcrystalline cellulose, pyrantel and corn starch to obtain a primary mixture; Re-mixing: adding the formula amount of praziquantel pyrantel pamoate, cross-linked povidone to the primary mixture for mixing to obtain a re-mixture; Total mixing: adding the formula amount of magnesium stearate to the re-mixture for mixing to obtain a total mixture; Tablet pressing and coating: tablet pressing the total mixture to obtain a praziquantel pyrantel pamoate tablet core; coating the praziquantel pyrantel pamoate tablet core with a coating material to obtain a praziquantel pyrantel pamoate tablet.

[0025] Preferably, the components of the praziquantel pyrantel pamoate tablet further include polyvinylpyrrolidone, and the preparation method comprises the following steps: Pre-treatment: dissolving the polyvinylpyrrolidone in ethanol, then adding praziquantel pyrantel pamoate and stirring to a paste, drying at 60°C under reduced pressure, and crushing to pass through an 80-mesh sieve to obtain pre-treated particles; Primary mixing: mixing the formula amount of microcrystalline cellulose, pyrantel and corn starch to obtain a primary mixture; Remix: the formula amount of pretreated particles, crosslinked povidone is added to the premix for mixing to obtain a remix; Total mixing: the formula amount of magnesium stearate is added to the remix for mixing to obtain a total mixture; Tablet coating: the total mixture is tableted to obtain a pyrantel pamoate tablet core; the pyrantel pamoate tablet core is coated with a coating material to obtain a pyrantel pamoate tablet.

[0026] By adopting the above technical scheme, the polyvinylpyrrolidone is stretched in ethanol, penetrates the drug crystal defects, and forms a hydrogen bond anchoring network. The reduced pressure drying forms a honeycomb structure, improves the specific surface area, and thus improves the dissolution level of pyrantel pamoate and pyrantel.

[0027] In summary, the present application has the following beneficial effects: 1. Since the crosslinked povidone swells in water in the present application, the pyrantel pamoate tablet is rapidly disintegrated into fine particles in a short time, the dissolution level of pyrantel pamoate and pyrantel is improved; microcrystalline cellulose and corn starch can cooperate with each other to further improve the water absorption swelling rate and promote the disintegration effect of crosslinked povidone; 2. The present application can also add copovidone, which can wrap pyrantel fine powder into pseudo-particles, eliminate static migration, and reduce the possibility of pyrantel drug segregation; copovidone dissolves to form microporous channels when it comes into contact with water, accelerating the penetration of the medium into the tablet core, which helps the crosslinked povidone to absorb water and disintegrate; 3. The present application can also add polyvinylpyrrolidone, which can directly wet pyrantel and other substances to form a drug complex, while eliminating static electricity and reducing the possibility of segregation of each component; when it comes into contact with water, it can quickly dissolve to form a hydrophilic microporous network, improve the medium penetration rate, and at the same time maintain the opening of the pores to prevent the crosslinked povidone water absorption channel from being blocked and promote disintegration. DETAILED DESCRIPTION

[0028] The raw materials in the present application include the following parts: Pyrantel pamoate: a commercially available product with CAS No. 22204-24-6 is used; Pyrantel pamoate: a commercially available product with CAS No. 22204-24-6 is used; Microcrystalline cellulose: a commercially available product with CAS No. 9004-34-6 is used; Corn starch: a commercially available product with CAS No. 9005-25-8 is used; Crosslinked povidone: a commercially available product with CAS No. 25249-54-1 is used; Magnesium stearate: a commercially available product with CAS No. 557-04-0 is used; Copolyvidone: commercially available product with CAS No. 25086-89-9; Polyvinylpyrrolidone: commercially available product with CAS No. 9003-39-8; Coating material: commercially available coating materials can be used, and ethyl cellulose (EC) - colloidal silicon dioxide is used as an example in the present application.

[0029] The present application is further described in detail below in combination with examples and comparative examples.

[0030] Example 1 A preparation method of a thiamone pyrantel pamoate tablet, comprising the following steps: Primary mixing: 30 g of microcrystalline cellulose, 20 g of pyrantel (D90 of 25 μm) and 45 g of corn starch are mixed to obtain a primary mixture; Secondary mixing: 230 g of thiamone pyrantel pamoate, 4 g of cross-linked polyvidone are added to the primary mixture and mixed to obtain a secondary mixture; Total mixing: 3 g of magnesium stearate is added to the secondary mixture and mixed to obtain a total mixture; Tabletting and coating: the total mixture is tabletted to obtain a thiamone pyrantel pamoate tablet core; the thiamone pyrantel pamoate tablet core is coated with 7 g of coating material to obtain a thiamone pyrantel pamoate tablet.

[0031] Examples 2-3 Examples 2-3 are based on the preparation method of Example 1, and the content of each component of the thiamone pyrantel pamoate tablet is adjusted, and the specific adjustment is shown in Table 1.

[0032] Comparative Examples 1-4 Comparative Example 1 is based on the preparation method of Example 1, and in the step of secondary mixing, 4 g of cross-linked polyvidone is not added.

[0033] Comparative Example 2 is based on the preparation method of Example 1, and in the step of primary mixing, 30 g of microcrystalline cellulose is not added, but 75 g of corn starch is added instead.

[0034] Comparative Example 3 is based on the preparation method of Example 1, and in the step of primary mixing, 30 g of corn starch is not added, but 75 g of microcrystalline cellulose is added instead.

[0035] Comparative Example 4 uses commercially available reagents, and the trade name is Bai Cheng Qing.

[0036] Performance detection test The thiamone pyrantel pamoate tablets of Examples 1-3 and Comparative Examples 1-4 are subjected to the following performance detection, and the detection results are shown in Table 1.

[0037] 1. Mixing uniformity Randomly sample 11 points on the pyrantel pamoate tablets, each point sample contains 0.1g, calculate the theoretical content A of pyrantel in the point sample, determine the content B of pyrantel in each point by high performance liquid chromatography, calculate the uniformity of pyrantel = (B / A) * 100%, calculate the average value and RSD of the uniformity of pyrantel by statistics of 11 points.

[0038] 2. Dissolution level Refer to dissolution and release determination method (Chinese Pharmacopoeia 2020 edition four general rules 0931 second method), with 0.1mol / L hydrochloric acid solution containing 0.5wt% sodium dodecyl sulfate 900mL as dissolution medium, the rotation speed is 100 revolutions per minute, determine the dissolution curve. Record the dissolution amount of pamoate and pyrantel at 10min and 45min. Calculate the proportion of the dissolution amount of the two substances at 10min and 45min.

[0039] 3. Stability Place the sample under accelerated conditions (temperature 40℃±2℃, RH 75%±5%) for 6 months, and then refer to dissolution and release determination method (Chinese Pharmacopoeia 2020 edition four general rules 0931 second method), with 0.1mol / L hydrochloric acid solution containing 0.5wt% sodium dodecyl sulfate 900mL as dissolution medium, the rotation speed is 100 revolutions per minute, record the dissolution amount of pamoate and pyrantel at 45min, calculate the proportion of the dissolution amount of the two substances.

[0040] Table 1 content of each component of pamoate pyrantel tablets of examples 1-3 and comparative examples 1-4 (unit: g) and performance test table As shown in Table 1, comparative examples 1-3 and comparative examples 1-4, the formula needs to have crosslinked polyvinylpyrrolidone, microcrystalline cellulose and corn starch at the same time, in order to have excellent results. The reason is that crosslinked polyvinylpyrrolidone can swell rapidly after water, disintegrating pamoate pyrantel tablets into fine particles in a short time, greatly increasing the contact area of the drug and body fluid, and improving the dissolution level of pamoate and pyrantel. Microcrystalline cellulose can effectively adsorb pyrantel particles to prevent them from segregating. Microcrystalline cellulose can also improve the compressibility of particles and form a porous network. The porous structure can accelerate water penetration when it meets water, which can assist the water absorption and swelling of crosslinked polyvinylpyrrolidone. Corn starch can occupy the gap between particles when mixed, buffer the density difference between substances, and improve the flowability. When corn starch is used with microcrystalline cellulose, it can further increase the water absorption and swelling rate, adjust the porosity of the tablets, and promote the disintegration effect of crosslinked polyvinylpyrrolidone.

[0041] In addition, it is found that the performance of Example 1 is the best among Comparative Examples 1-3, and thus, Example 1 is preferred.

[0042] Examples 4-5 Examples 4-5 are based on the preparation method of Example 1, and the particle size of praziquantel is adjusted, and the specific adjustment is shown in Table 2.

[0043] The pyrantel pamoate tablets of Examples 4-5 are subjected to the performance test as above, and the test results are shown in Table 2.

[0044] Table 2 Particle size of praziquantel and performance test table of Examples 1 and 4-5 As shown in Table 2, by comparing Comparative Example 1 with Examples 4-5, it is found that as the particle size of praziquantel is continuously reduced, the performance of the pyrantel pamoate tablets is continuously increased. The reason is that the proportion of praziquantel is low, and reducing the particle size can significantly increase the number of particles and greatly improve the spatial distribution density. The surface of microcrystalline cellulose is rough and porous, and small particle size praziquantel can be embedded in the pores of microcrystalline cellulose by mechanical anchoring effect, reducing the separation tendency. Reducing the particle size of praziquantel can expand the dissolution interface, increase the contact probability with the solvent, and overcome the low solubility barrier. When cross-linked povidone absorbs water and disintegrates, a flocculent aggregate is generated, and small particle size praziquantel can be embedded therein, directly exposed to the solvent.

[0045] Examples 6-7 Examples 6-7 are based on the preparation method of Example 1, and the mass ratio of microcrystalline cellulose to corn starch is 75 g, and the mass ratio of microcrystalline cellulose to corn starch is adjusted, and the specific adjustment is shown in Table 3.

[0046] The pyrantel pamoate tablets of Examples 6-7 are subjected to the performance test as above, and the test results are shown in Table 3.

[0047] Table 3 Mass ratio of microcrystalline cellulose to corn starch and performance test table of Examples 1 and 6-7 As shown in Table 3, by comparing Comparative Example 1 with Examples 6-8, it is found that when the content proportion of corn starch is higher and higher, the performance of the pyrantel pamoate tablets shows a trend of first increasing and then decreasing. The reason is that when the content proportion of corn starch is higher and higher, the dispersion effect is better and better, and after the disintegration of each component, it is not easy to aggregate, the dissolution level is increased, the adhesion is enhanced, and the stability is improved. When it exceeds a certain range, the excess starch forms a continuous phase, and praziquantel is easily physically isolated, which can easily reduce the uniformity; too much corn starch can easily form a high-viscosity gel layer, which can block the diffusion of the drug and reduce the performance.

[0048] Examples 8-9 Example 8-9 Based on the preparation method of Example 1, the mass ratio of crosslinked povidone to magnesium stearate is 7 g, and the mass ratio of crosslinked povidone to magnesium stearate is adjusted. The specific adjustment is shown in Table 4.

[0049] The performance of the pyrantel pamoate tablets of Examples 8-9 is tested as above, and the test results are shown in Table 4, respectively.

[0050] Table 4 Performance test table of Examples 1 and 8-9 As shown in Table 4, by comparing Example 1 and Examples 8-9, it can be seen that when the content of magnesium stearate increases, the performance of the pyrantel pamoate tablets first increases and then decreases. The reason is that when the content of magnesium stearate increases, the lubricating effect between the components is enhanced, thereby improving the performance of the pyrantel pamoate tablets. When it exceeds a certain range, the excess magnesium ions neutralize the negative charges of the crosslinked povidone, the crosslinked povidone loses the electrostatic repulsion and is easy to form large particle size clumps; the crosslinked povidone is wrapped by magnesium stearate, the water swelling space is lost, and the disintegration effect is reduced, thereby reducing the dissolution level of the medicine.

[0051] Example 10-12 Example 10 Based on the preparation method of Example 1, the remixing step is adjusted as follows: 230 g of pyrantel pamoate, 4 g of crosslinked povidone, and 6 g of copovidone are added to the premix for mixing to obtain a remix.

[0052] Examples 11-12 Based on the preparation method of Example 10, the amount of copovidone added is adjusted, and the specific adjustment is shown in Table 5.

[0053] The performance of the pyrantel pamoate tablets of Examples 10-12 is tested as above, and the test results are shown in Table 5, respectively.

[0054] Table 5 Copovidone addition amount and performance test table of Examples 1 and 10-12 As shown in Table 5, by comparing Example 1 and Examples 10-12, it can be seen that the additional addition of copovidone in the formula can further improve the performance of the pyrantel pamoate tablets. The reason is that copovidone can wrap pyrantel pamoate fine powder into pseudo-particles, eliminate electrostatic migration, and reduce the possibility of pyrantel pamoate drug segregation. Copovidone dissolves to form microporous channels when it comes into contact with water, accelerating the penetration of the medium into the tablet core, which helps the crosslinked povidone to absorb water and disintegrate.

[0055] When the amount of copolyvidone is increased, the performance of the praziquantel pyrantel pamoate tablet shows a trend of first increasing and then decreasing. The reason is that when the amount of copolyvidone is increased, the copolyvidone continuously reduces the possibility of praziquantel drug segregation and promotes the water absorption and disintegration of cross-linked polyvidone, thereby improving the performance of the praziquantel pyrantel pamoate tablet. When it exceeds a certain range, the cross-linked polyvidone is trapped by the high-viscosity solution, reducing the swelling rate and thus reducing the drug dissolution level.

[0056] Examples 13-17 Example 13 is based on the preparation method of Example 1, and the preparation steps are adjusted as follows: Pre-treatment: 75 g of polyvinylpyrrolidone is dissolved in 750 mL of ethanol, then 230 g of pyrantel pamoate is added and stirred into a paste, dried at 60°C under reduced pressure, and pulverized through an 80-mesh sieve to obtain pre-treatment particles; Primary mixing: 30 g of microcrystalline cellulose, 20 g of praziquantel (D90 of 25 μm), and 45 g of corn starch are mixed to obtain a primary mixture; Re-mixing: the pre-treatment particles, 4 g of cross-linked polyvidone, are added to the primary mixture and mixed to obtain a re-mixture; Total mixing: 3 g of magnesium stearate is added to the re-mixture and mixed to obtain a total mixture; Tabletting and coating: the total mixture is tabletted and coated to obtain a praziquantel pyrantel pamoate tablet core; the praziquantel pyrantel pamoate tablet core is coated with 7 g of coating material to obtain a praziquantel pyrantel pamoate tablet.

[0057] Examples 14-15 are based on the preparation method of Example 13, and the amount of polyvinylpyrrolidone is adjusted, as shown in Table 6.

[0058] Example 16 is based on the preparation method of Example 1, and the re-mixing step is adjusted as follows: 230 g of pyrantel pamoate, 4 g of cross-linked polyvidone, and 75 g of polyvinylpyrrolidone are added to the primary mixture and mixed to obtain a re-mixture.

[0059] Example 17 is based on the preparation method of Example 13, and the re-mixing step is adjusted as follows: The pre-treatment particles, 4 g of cross-linked polyvidone, and 6 g of copolyvidone are added to the primary mixture and mixed to obtain a re-mixture.

[0060] The praziquantel pyrantel pamoate tablets of Examples 13-17 are subjected to the performance test as above, and the test results are shown in Table 6, respectively.

[0061] Table 6: Amount of polyvinylpyrrolidone and performance test table of Example 1 and Examples 13-17 As shown in Table 6, the additional polyvinylpyrrolidone in the formulation of Comparative Example 1 and Examples 13-17 can further improve the performance of praziquantel pyrantel pamoate tablets. The reason is that polyvinylpyrrolidone can directly wet substances such as praziquantel to form a drug complex, while eliminating static electricity and reducing the possibility of component segregation. When water is encountered, it can quickly dissolve to establish a hydrophilic microporous network, improve medium permeation rate, and at the same time maintain pore opening to prevent cross-linked povidone water absorption channel from being blocked, promote disintegration. Polyvinylpyrrolidone can form a glassy film to reduce oxygen permeation, thereby maintaining the overall stability of the drug.

[0062] When the amount of polyvinylpyrrolidone added is higher and higher, the performance of praziquantel pyrantel pamoate tablets shows a trend of first increasing and then decreasing. The reason is that when the amount of polyvinylpyrrolidone added is higher and higher, the promotion effect on each component is better and better, thereby improving the performance of praziquantel pyrantel pamoate tablets. When it exceeds a certain range, polyvinylpyrrolidone is easy to form a continuous film, and the fluidity between components decreases; after water absorption, a high-viscosity gel layer is formed, the diffusion coefficient decreases, and the cross-linked povidone is imprisoned after water absorption and swelling, resulting in difficult disintegration and reduced dissolution level; it is easy to absorb moisture in the air during storage and be imprisoned in the tablet, accelerating hydrolysis.

[0063] In addition, the effect is better when polyvinylpyrrolidone is added to pretreat praziquantel pamoate. In addition, on this basis, the effect is better when copovidone is additionally added.

[0064] The specific embodiments are merely an explanation of the present application, which is not a limitation of the present application. Those skilled in the art can make modifications to the embodiments without creative contribution after reading the specification, as long as the modifications are within the scope of the claims of the present application.

Claims

1. A pyraquinone dihydroxynaphthyl thiamethoxam tablet, characterized in that, The product comprises the following components in parts by weight: 230 parts of pamoate, 20 parts of praziquantel, 75 parts of filler, 2-5 parts of crospovidone, 2-10 parts of copovidone, 3-4 parts of magnesium stearate, and 7-11 parts of coating material; the filler comprises 20-55 parts of microcrystalline cellulose and 20-55 parts of corn starch; the mass ratio of microcrystalline cellulose to corn starch is 1:0.8-2; and the mass ratio of crospovidone to copovidone is 1:1-2.

2. The bis(hydroxynaphthyl)pyraquinone tablets according to claim 1, characterized in that: The particle size of the praziquantel is D90≤50μm.

3. The pyraquinone pamoate tablets according to claim 1, characterized in that: The mass ratio of cross-linked polyvinylpyrrolidone to magnesium stearate is 4:2-4.

4. The pyraquinone pamoate tablets according to claim 1, characterized in that: It also includes polyvinylpyrrolidone.

5. The bis(hydroxynaphthyl)pyraquinone tablets according to claim 4, characterized in that: The polyvinylpyrrolidone is in the form of 50-85 parts by weight.

6. The method for preparing the dihydroxynaphthylpyrazine praziquantel tablets according to any one of claims 1-3, characterized in that: Preliminary Mixture: Mix the prescribed amounts of microcrystalline cellulose, praziquantel, and corn starch to obtain the preliminary mixture; Remix: Add the prescribed amounts of bis(hydroxynaphthyl)pyrazine and crospovidone to the primary mixture and mix to obtain the remix; Total Mixture: Add the specified amount of magnesium stearate to the remixing material and mix to obtain the total mixture; Tablet Coating: The total mixture is compressed into tablets to obtain pyraquinone pamoate tablet cores; The core of the dihydroxynaphthylpyrazine tablet was coated with a coating material to obtain dihydroxynaphthylpyrazine tablets.

7. The method for preparing bis(hydroxynaphthyl)pyraquinone tablets according to claim 6, characterized in that: The components of the dihydroxynaphthylpyrazine praziquantel tablets also include polyvinylpyrrolidone, and the preparation method includes the following steps: Pretreatment: Dissolve polyvinylpyrrolidone in ethanol, then add bis(hydroxynaphthyl)thiamethoxam and stir until a paste is formed. Dry under reduced pressure at 60°C, then pulverize and pass through an 80-mesh sieve to obtain pretreated granules. Preliminary Mixture: Mix the prescribed amounts of microcrystalline cellulose, praziquantel, and corn starch to obtain the preliminary mixture; Remix: Add the pretreated granules and cross-linked polyvinyl ketone to the primary mixture and mix to obtain the remix; Total Mixing: The amount of magnesium stearate in the formula is added to the remixing material and mixed to obtain the total mixture; Tableting and Coating: The total mixture is compressed into tablets to obtain bis(hydroxynaphthylpyridinium) pyrazinol tablet cores; The bis(hydroxynaphthylpyridinium) pyrazinol tablet cores are coated with a coating material to obtain bis(hydroxynaphthylpyridinium) pyrazinol tablets.

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