Medicinal slow-release antistatic coating liquid as well as preparation method and application thereof

Abstract

The invention discloses a medicinal slow-release antistatic coating solution and a preparation method and application thereof, and belongs to the technical field of medicinal preparations, the medicinal slow-release antistatic coating solution comprises the following components by weight: 1.2-2.0% of an anti-sticking agent; 0.4%-0.8% of a plasticizer; 0.04 to 0.22% of a lubricant; 3.0 to 5.0 percent of ethyl cellulose; the balance is ethanol or an ethanol aqueous solution; and the lubricant is long-chain saturated fatty acid or long-chain saturated fatty glyceride with the carbon number of C12-C22. The coating liquid has an antistatic effect and can obviously improve electrostatic adsorption and particle bonding phenomena in the coating process, small-diameter medicine particles are coated by using the coating liquid, a prepared coating film is complete, smooth and crack-free, the slow-release effect is good, enteric slow-release particles and orally disintegrating tablets can be prepared after an enteric coating is further overlaid, and the application range is wide. And the preparation method has a good application prospect in the development of small-diameter functional particles and orally disintegrating tablets.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a medicinal sustained-release antistatic coating liquid and a preparation method and application thereof. Background Art

[0002] Sustained-release coating is a coating technology used to prepare film-controlled sustained-release preparations. The coating film formed by the sustained-release coating film-forming material will swell to a certain extent when in contact with water, but will not dissolve. Water penetrates into the interior through the pores of the coating film, dissolves the drug components, and forms a concentration difference in the liquid environment on both sides of the film, which serves as the driving force for drug release. The drug release behavior can be regulated by adjusting the composition and preparation process of the coating film.

[0003] Sustained-release coating solutions include aqueous dispersion systems and organic solvent systems. The aqueous dispersion coating system is safe and environmentally friendly, but the prepared sustained-release coating film has poor density and requires several times the weight gain to achieve the same sustained-release effect compared to the organic coating system. Studies have reported that when taking particles with a diameter greater than 200 μm, there will be a gritty feeling in the mouth, and the drug particles used for orodisintegrating tablets must be smaller than this limit. Small-diameter drug particles have a larger specific surface area. Compared with drug pellets, a higher weight gain ratio is required to ensure a sustained-release effect. The use of an organic coating system can greatly reduce the use of coating materials and reduce the risk of exceeding the particle size limit of the coated particles.

[0004] During the fluidized bed coating process, static electricity will be generated by friction between material particles, between the material and the inner wall of the container, and between the wind and the material. Organic solvents have poor conductivity, and static electricity gradually accumulates as the coating process proceeds, which in turn causes adhesion between particles and between particles and the inner wall of the container, affecting the coating process and the quality of the coating film, as well as subsequent material transfer, packaging, weighing and other processes. Compared with drug pellets, the uneven fluidization, static adhesion, and particle bonding during the coating process of small-diameter drug particles are more serious, becoming a technical bottleneck that needs to be overcome urgently. Therefore, it is necessary to develop a coating solution that can reduce static electricity during the fluidized bed coating process of microparticles, and the coating film formed is dense and has a good sustained-release effect.

[0005] In existing organic sustained-release coating liquid formulations, there are high molecular polymers, organic solvents, plasticizers, anti-sticking agents, etc. During the fluidized bed coating process, static electricity is easily generated, which not only affects the coating process but also poses safety hazards. Chinese patent document with publication number CN104248766A discloses a coating liquid containing ethyl cellulose with dichloromethane as the solvent. This coating liquid includes: 1% - 3% (w / w) of ethyl cellulose, 0.1% - 0.3% (w / w) of hydroxypropyl methylcellulose, 1% - 5% (w / w) of purified water, and 92% - 98% (w / w) of dichloromethane. This coating liquid can effectively reduce the strong static electricity generated by the mutual friction of pellets during coating. However, the effect of this coating liquid has only been verified on drug-containing pellets with a diameter of 500 - 600 μm, and it is unknown how it works on smaller drug particles. Moreover, this coating liquid uses dichloromethane as the solvent, which has relatively high toxicity. Chinese patent document with publication number CN102697660A discloses a method for removing static electricity between pellets. This method sprays 0.03 - 0.05 wt% of medicinal soybean oil based on the mass of the pellets into the coating granulator after the pellet coating is completed to reduce friction and remove static electricity. However, this method only targets the static electricity on the surface of the pellets after coating and cannot eliminate the static electricity generated during the coating process, having certain limitations.

[0006] Tamsulosin hydrochloride is a drug clinically used to treat male prostate hyperplasia and lower urinary tract symptoms. Due to the characteristic of long-term medication required for prostate hyperplasia, formulating it into a sustained-release preparation can reduce the frequency of medication, maintain a stable blood drug concentration, and avoid side effects such as dizziness and hypotension. Since it is difficult to develop a functional coating for small-diameter drug particles, there is currently no domestically self-developed orally disintegrating tablet dosage form drug with tamsulosin hydrochloride as the active ingredient. Therefore, it is necessary to develop an enteric-coated sustained-release microparticle of tamsulosin hydrochloride. Summary of the Invention

[0007] In order to solve the deficiencies existing in the above-mentioned prior art, the present invention provides a medicinal sustained-release antistatic coating liquid. This coating liquid has an antistatic effect and can significantly improve the static electricity adsorption and particle bonding phenomena during the coating process. Using this coating liquid to coat small-diameter drug microparticles, a coating film with a complete and smooth surface without cracks and good sustained-release effect can be prepared.

[0008] The specific technical solution adopted is as follows:

[0009] A medicinal sustained-release antistatic coating liquid, and the medicinal sustained-release antistatic coating liquid is composed of the following components in weight percentages:

[0010]

[0011] The balance is ethanol or an aqueous ethanol solution;

[0012] The lubricant is a long-chain saturated fatty acid or long-chain saturated fatty acid glyceride with 12 to 22 carbon atoms.

[0013] The coating solution with specific components provided by the present invention uses a long-chain saturated fatty acid or long-chain saturated fatty acid glyceride with 12 to 22 carbon atoms and in a solid state at room temperature as the lubricant. The addition of the corresponding lubricant can lubricate the surface of drug particles, reduce the generation of static electricity by reducing the friction between particles and between particles and the inner wall of the container during the fluidized bed coating process, improve the phenomena of static adsorption and particle adhesion, and ensure the continuous and stable progress of the coating process.

[0014] The anti-adhesive agent includes talc, magnesium stearate or colloidal silica; preferably, the anti-adhesive agent is talc.

[0015] The plasticizer includes dibutyl phthalate, triethyl citrate or polyethylene glycol (specifically, polyethylene glycol 400 can be selected); preferably, the plasticizer is dibutyl phthalate.

[0016] Optionally, the long-chain saturated fatty acid is selected from lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid or behenic acid, and the long-chain saturated fatty acid glyceride is a monoglyceride, diglyceride or triglyceride formed by condensation of any one of the above long-chain saturated fatty acids with glycerol; further preferably, the lubricant is glycerol monostearate.

[0017] Preferably, the concentration of the ethanol aqueous solution is 80% - 95% (volume fraction of ethanol).

[0018] The present invention also provides a preparation method of the medicinal sustained-release antistatic coating solution, including the following steps: taking ethanol or an ethanol aqueous solution, adding the prescribed amount of ethyl cellulose, and fully dissolving it to obtain an ethyl cellulose solution; weighing the prescribed amount of lubricant, dissolving it in ethanol and then adding it to the ethyl cellulose solution, mixing evenly to obtain a mixed solution, and successively adding the prescribed amount of plasticizer and anti-adhesive agent to the mixed solution, and mixing evenly to obtain the medicinal sustained-release antistatic coating solution.

[0019] Specifically, the lubricant is dissolved in ethanol according to the dosage ratio of 0.6 - 3 g: 5 mL, and then added to the ethyl cellulose solution.

[0020] The present invention also provides an enteric-coated sustained-release drug particle, the structure of which includes a drug-loaded particle, a sustained-release coating and an enteric coating arranged in sequence from the inside to the outside, and the sustained-release coating is prepared from the medicinal sustained-release antistatic coating solution.

[0021] Preferably, the active ingredient of the drug-loaded particle is tamsulosin hydrochloride.

[0022] In order to ensure that there is no gritty feeling in the mouth after taking the enteric-coated sustained-release drug particles, the particle size range needs to be controlled within 50 - 350 μm.

[0023] Preferably, the enteric coating is prepared from an enteric coating solution containing an enteric coating material, a plasticizer, and an anti-sticking agent. The enteric coating material is selected as the copolymer of methacrylic acid and ethyl acrylate.

[0024] The present invention also provides an orally disintegrating tablet of tamsulosin hydrochloride, which contains enteric-coated sustained-release particles of tamsulosin hydrochloride.

[0025] Preferably, the orally disintegrating tablet of tamsulosin hydrochloride further includes an orally disintegrating composite excipient (which can be purchased) and a lubricant for tableting. The orally disintegrating composite excipient is a physical composition of a saccharide filler (such as microcrystalline cellulose, mannitol, starch, sucrose, lactose, etc.) and a disintegrant (such as sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone, etc.). The lubricant for tableting is selected from stearic acid, stearate, talc powder, hydrogenated vegetable oil, polyethylene glycol, sodium dodecyl sulfate, magnesium dodecyl sulfate, etc., and preferably stearic acid or stearate.

[0026] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0027] (1) The present invention uses a long-chain saturated fatty acid or long-chain saturated fatty acid glyceride with 12 - 22 carbon atoms and being solid at room temperature as a lubricant to prepare a coating solution of specific components. The fluidized bed coating is carried out on the material with this coating solution. During the coating process, the fluidization state of the material is good, the electrostatic adsorption rate is reduced by 5% - 30%, and the particle adhesion rate is reduced by 20% - 40%. The coating process can be carried out continuously and stably, especially suitable for small-diameter drug particles. Compared with the existing antistatic sustained-release coating solution using dichloromethane as a solvent, using ethanol as the solvent of the organic coating system is safer and more environmentally friendly.

[0028] (2) Using the medicinal sustained-release antistatic coating solution of the present invention to coat tamsulosin hydrochloride particles, the prepared tamsulosin hydrochloride sustained-release particles have a round shape and a smooth film without cracks, and have a good drug release delaying effect. Further coating an enteric layer on the tamsulosin hydrochloride sustained-release particles to obtain enteric-coated sustained-release particles of tamsulosin hydrochloride, whose particle size is below 200 μm and has no gritty feeling. While superimposing the enteric function, it does not affect the sustained-release effect, and can be further used to prepare an orally disintegrating tablet of tamsulosin hydrochloride, providing a reference for the development of small-diameter functional particles and new orally disintegrating tablets. Description of the Drawings

[0029] Figure 1 In vitro cumulative release curves of tamsulosin hydrochloride sustained-release particles with 7%, 14%, 21%, and 28% weight gain of the sustained-release layer in Example 3 in PBS (pH 6.8).

[0030] Figure 2 In vitro cumulative release curves of tamsulosin hydrochloride-loaded microparticles, tamsulosin hydrochloride sustained-release microparticles and tamsulosin hydrochloride enteric-coated sustained-release microparticles in Example 3 in PBS (pH 6.8).

[0031] Figure 3 Scanning electron micrograph of tamsulosin hydrochloride sustained-release microparticles in Example 3, where B is an enlarged view of A.

[0032] Figure 4 In vitro cumulative release curves of tamsulosin hydrochloride enteric-coated sustained-release microparticles in Example 3 and tamsulosin hydrochloride orally disintegrating tablets in Example 4 in PBS (pH 6.8).

[0033] Figure 5 Drug release amounts of tamsulosin hydrochloride enteric-coated sustained-release microparticles in Example 3 and tamsulosin hydrochloride orally disintegrating tablets in Example 4 in hydrochloric acid-sodium chloride solution (pH 2.0) for 2 h. Among them, A is the high-performance liquid chromatography (HPLC) chromatogram of the standard solution (C = 0.02 μg / mL), B is the HPLC chromatogram of tamsulosin hydrochloride enteric-coated sustained-release microparticles, and C is the HPLC chromatogram of tamsulosin hydrochloride orally disintegrating tablets.

[0034] Figure 6 Cross-sectional scanning electron micrograph of tamsulosin hydrochloride orally disintegrating tablets in Example 4. Detailed implementation manners

[0035] To make the objectives, features and advantages of the present invention more obvious and understandable, the following provides a detailed description through specific implementation manners. Many specific details are set forth in the following description to fully understand the present invention. However, the present invention can be implemented in many other ways different from those described herein, and those skilled in the art can make similar improvements without departing from the connotation of the present invention. Therefore, the present invention is not limited by the specific embodiments disclosed below. The technical features in each embodiment of the present invention can be combined correspondingly without conflict.

[0036] For the operation methods without specific conditions noted in the following examples, they are generally in accordance with conventional conditions or the conditions recommended by the manufacturer. The content not described in detail in this specification belongs to the prior art well-known to those skilled in the art. The experimental materials used in the following examples can be obtained from conventional biochemical reagent companies without special instructions.

[0037] Example 1: Preparation of a medicinal sustained-release antistatic coating solution

[0038] Take 252 g of purified water and 1008 g of absolute ethanol, mix them evenly to prepare an ethanol solution with a volume fraction of 80%. Slowly add 63 g of ethyl cellulose to it and stir overnight until completely dissolved to obtain a pale yellow, clear and transparent ethyl cellulose solution. Weigh accurately the prescribed amount of lubricant, dissolve it in a small amount of ethanol and then drop it into the ethyl cellulose solution and mix well (the prescribed amount of lubricant is shown in Table 1, where Prescription F10 is used as a control and no lubricant-ethanol mixture is added to the ethyl cellulose solution). Then, add 9.45 g of plasticizer dibutyl phthalate and 25.2 g of anti-adhesive ultrafine talc powder in sequence. Homogenize with a high-shear homogenizer at 8000 rpm for 10 min to obtain a coating solution, and keep stirring to prevent the talc powder from settling. The specific prescription compositions of Prescriptions F1 - F10 are shown in Table 1.

[0039] Table 1 Coating solution formula for Prescriptions F1 - F10

[0040]

[0041] Evaluation of antistatic effect of coating solution in Example 2

[0042] Using the fluidized bed side spray technology, coat the mannitol pill cores with a particle size of about 100 μm respectively with the coating solutions of Prescriptions F1 - F10 in Example 1. During the coating process, control the inlet air temperature at 35 °C, the atomization pressure at 0.20 MPa, coat for 1 h for each group. After completion, collect the fine particles and pass them through a sieve with a pore size of 200 μm, and calculate the following parameters:

[0043] (1) Electrostatic adhesion rate:

[0044] Electrostatic adhesion rate % = mass of fine particles adhered to the wall of the fluidized bed barrel / total mass of fine particles * 100%;

[0045] (2) Electrostatic adhesion change rate:

[0046] Electrostatic adhesion change rate % = (electrostatic adhesion rate of the experimental group - electrostatic adhesion rate of the control group) / electrostatic adhesion rate of the control group * 100%;

[0047] (3) Fine particle bonding rate:

[0048] Bonding rate % = mass of fine particles not passing through the sieve / total mass of fine particles * 100%;

[0049] (4) Fine particle bonding change rate:

[0050] Bonding change rate % = (bonding rate of the experimental group - bonding rate of the control group) / bonding rate of the control group * 100%;

[0051] The test results of the electrostatic adhesion rate and change rate, and the fine particle bonding rate and change rate during the coating process of groups F1 - F10 are shown in Table 2.

[0052] Table 2 Evaluation of antistatic effect of coating solutions of prescriptions F1 to F10

[0053]

[0054] The results showed that compared with the F10 group without lubricant, the electrostatic adsorption rate and particle bonding rate of the F1-F9 groups with lubricant were significantly reduced, with the reduction ratios ranging from 5% to 30% and 20% to 40%, respectively. Compared with the three long-chain fatty acids monostearate, lauric acid and stearic acid, the effect of monostearate in reducing electrostatic adhesion and particle bonding was slightly better than that of stearic acid and lauric acid, which may be related to its conductivity.

[0055] Example 3 Preparation and evaluation of tamsulosin hydrochloride enteric-coated sustained-release microparticles

[0056] (1) Preparation of drug-loaded microparticles

[0057] Using tamsulosin hydrochloride as a model drug, the drug-loaded microparticles were prepared by the fluidized bed side spraying method. 2.4 g of tamsulosin hydrochloride was accurately weighed and magnetically stirred to completely dissolve it in 1000 g of 70°C purified water to obtain a drug solution. 30 g of hydroxypropyl methylcellulose was added to the drug solution, stirred in a hot water bath until the solid was completely dissolved, transferred to room temperature and continued to stir until the solution was clear, and used as the drug solution for standby. 300 g of mannitol pellets with a particle size of about 100 μm were weighed, and the drug solution was sprayed onto the surface of the pellets. The air inlet temperature was set at 55-60°C during the process. The particle size of the obtained tamsulosin hydrochloride drug-loaded microparticles was 108.54±20.79 μm.

[0058] (2) Preparation of sustained-release coating

[0059] By using the fluidized bed side spray technology, 300 g of the prepared tamsulosin hydrochloride drug-loaded microparticles were coated with the medicinal sustained-release antistatic coating liquid of prescription F2 in Example 1. During the coating process, the inlet air temperature was controlled to be 35° C. and the atomization pressure was 0.20 MPa. Tamsulosin hydrochloride sustained-release microparticles with a sustained-release layer weight gain of 28% were prepared, which were further used for the preparation of enteric-coated sustained-release drug microparticles.

[0060] (3) Preparation of enteric-coated sustained-release drug microparticles

[0061] According to the preparation method in the Eudragit manual, 1620g of ethanol and 180g of purified water were mixed to prepare a 90% ethanol solution. The above ethanol solution was divided into two parts. One part was added with 15g of triethyl citrate and 36g of ultrafine talcum powder in turn, and homogenized with a high-pressure disperser at 6000rpm for 10 minutes; the other part of the ethanol solution was added with 120g L100 - 55, stir until completely dissolved. While stirring, pour in the homogeneously prepared talcum powder suspension, and stir to mix evenly to obtain an enteric - coating solution for standby. Take 300 g of the tamsulosin hydrochloride sustained - release microparticles prepared in step (2) for enteric - layer coating. During the coating process, maintain the air supply temperature at 25 - 28 °C, and collect the microparticles with an enteric - coating weight gain of 50%. The particle size of the obtained enteric - coated tamsulosin hydrochloride sustained - release microparticles is 164.11 ± 16.24 μm.

[0062] (4) Sample testing and analysis

[0063] Preparation of tamsulosin hydrochloride sustained - release microparticles with different weight gains of the sustained - release layer: By measuring the mass difference of the coating solution before and after coating, and multiplying it by the proportion of the mass of ethyl cellulose in the total mass of the coating solution, the weight gain of the sustained - release layer of the microparticles is calculated by the indirect method. Collect tamsulosin hydrochloride sustained - release microparticles with weight gains of 7%, 14%, 21%, and 28% of the sustained - release layer. The particle size of the obtained tamsulosin hydrochloride sustained - release microparticles with a weight gain of 28% of the sustained - release layer is 149.43 ± 17.61 μm.

[0064] Determination of dissolution in PBS (pH 6.8): Use PBS (pH 6.8) as the release medium to simulate the intestinal environment. The determination method is formulated with reference to the existing technology. The paddle method is used, the rotation speed is 100 rpm, and the temperature is (37 ± 0.5) °C. Weigh an appropriate amount of the microparticles to be tested precisely. Sampling 4 mL at 0.25, 0.5, 1, 2, 4, and 6 h respectively, and supplement the same volume of dissolution medium. For each sample solution, accurately measure 2 mL, add 0.2 mL of 0.5 M hydrochloric acid solution, shake well, filter through a 0.22 - μm PES filter membrane, and determine the peak area by high - performance liquid chromatography at a wavelength of 225 nm. Substitute into the standard curve equation to calculate the corresponding drug concentration and cumulative release percentage.

[0065] The in vitro cumulative release curves of tamsulosin hydrochloride enteric - coated sustained - release microparticles with weight gains of 7%, 14%, 21%, and 28% of the sustained - release layer in PBS (pH 6.8) are as Figure 1 shown.

[0066] The in vitro cumulative release curves of tamsulosin hydrochloride - loaded microparticles, tamsulosin hydrochloride sustained - release microparticles, and tamsulosin hydrochloride enteric - coated sustained - release microparticles in PBS (pH 6.8) are as Figure 2 shown.

[0067] The results show that the sustained - release coating prepared with the pharmaceutical sustained - release antistatic coating solution has an obvious sustained - release effect. With the progress of the sustained - release coating process, the sustained - release effect of the microparticles gradually increases, indicating that the sustained - release coating process has good continuity. The tamsulosin hydrochloride sustained - release microparticles can continue to be overlaid with an enteric - coating layer, which can endow the drug microparticles with acid - resistance without affecting the drug - release - delaying effect of the sustained - release coating layer.

[0068] Morphological characterization of microparticles: An appropriate amount of the prepared tamsulosin hydrochloride sustained-release microparticles was fixed on the sample stage with carbon conductive adhesive, sputtered with platinum for 120 s, and the surface morphology was observed under a scanning electron microscope. The results are shown in Figure 3 .

[0069] The results showed that the surface coating film of the tamsulosin hydrochloride sustained-release microparticles prepared with the medicinal sustained-release antistatic coating solution of the present invention was intact, without depressions or cracks, indicating that the quality of the prepared coating film was relatively high, which was consistent with the sustained-release effect of the microparticles measured in PBS (pH 6.8).

[0070] Preparation and evaluation of tamsulosin hydrochloride orally disintegrating tablets in Example 4

[0071] The tamsulosin hydrochloride orally disintegrating tablets in this example were composed of the following raw materials: 6.8 g of the tamsulosin hydrochloride enteric-coated sustained-release microparticles in Example 3, 13.1 g of the commercially available orally disintegrating co-processed auxiliary material GRANFILLER-D TM D-211, and 60 mg of magnesium stearate.

[0072] Weigh the commercially available orally disintegrating composite auxiliary material GRANFILLER-D TM D-211, the tamsulosin hydrochloride enteric-coated sustained-release microparticles, and magnesium stearate, mix them evenly, select a mold with a diameter of 8 mm for tabletting, control the tablet hardness at 30 - 40 N, and prepare the tamsulosin hydrochloride orally disintegrating tablets.

[0073] The performance of the tamsulosin hydrochloride orally disintegrating tablets prepared in this example was detected by using conventional detection methods in the art:

[0074] (1) Using PBS (pH 6.8) as the release medium to simulate the small intestine environment, the dissolution was determined and compared with the tamsulosin hydrochloride enteric-coated sustained-release microparticles before tabletting. The results are as Figure 4 shown.

[0075] (2) Using hydrochloric acid - sodium chloride solution (pH 2.0) as the release medium to simulate the gastric environment, the acid resistance was determined. The determination method was formulated with reference to the prior art, paddle method, rotation speed was 100 rpm, temperature was (37 ± 0.5) °C. Take the prepared tamsulosin hydrochloride enteric-coated sustained-release microparticles and tamsulosin hydrochloride orally disintegrating tablets, sample at 2 h, filter through a 0.22 μm PES filter membrane, and use high performance liquid chromatography to determine the peak area at a wavelength of 225 nm, substitute it into the standard curve equation to calculate the corresponding drug concentration and release percentage. The results are as Figure 5 shown.

[0076] (3) Break the tamsulosin hydrochloride orally disintegrating tablets by an appropriate method, fix them on the sample stage with carbon conductive adhesive, sputter with platinum for 120 s, and observe the particle morphology under a scanning electron microscope. The results are shown in Figure 6 .

[0077] The research results showed that the release behavior of tamsulosin hydrochloride enteric-coated sustained-release microparticles before and after tabletting was basically the same in PBS (pH 6.8). After sampling in hydrochloric acid-sodium chloride solution (pH 2.0) for 2 hours, no peak was detected at the peak position of tamsulosin hydrochloride, which was lower than the method detection limit (0.02 μg / mL, corresponding to a drug release amount of 5%), indicating that the release amount was less than 5% and the acid resistance was good. The scanning electron microscope results showed that the coating film was intact and not broken, indicating that the coating film had flexibility and compressive resistance, and the coating film remained intact and unbroken during tabletting, and the functions of the sustained-release coating and enteric coating were not affected by the tabletting process.

[0078] (4) According to the requirements of the disintegration time limit inspection method for orally disintegrating tablets in the Chinese Pharmacopoeia 2020 Edition, an orally disintegrating tablet disintegration tester was used to determine the disintegration time limit. The disintegration time limit test results are shown in Table 3.

[0079] Table 3: Disintegration time limit determination results (n = 6)

[0080] Sample Mean(s) Tamsulosin Hydrochloride Orally Disintegrating Tablets 25.28±1.77s

[0081] The Pharmacopoeia stipulates that the sample should be completely disintegrated, dissolved or broken into fragments within 60 s, and should all pass through the sieve except for the insoluble coating material. If a small amount cannot pass through the sieve, but has softened or floated lightly and has no hard core, it can be considered in compliance. From Table 3, it can be seen that the orally disintegrating tablet of tamsulosin hydrochloride of the present invention complies with the Pharmacopoeia regulations.

[0082] The above-described embodiments have described the technical solutions of the present invention in detail. It should be understood that the above are only specific embodiments of the present invention and are not used to limit the present invention. Any modifications, supplements or similar replacements made within the scope of the principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A medicinal sustained-release antistatic coating solution, characterized in that: The medicinal sustained-release antistatic coating liquid is composed of the following components in percentage by weight: The balance is ethanol or ethanol-water solution; The lubricant is a long-chain saturated fatty acid or a long-chain saturated fatty acid glyceride with a carbon number of C12 to C22.

2. The medicinal sustained-release antistatic coating liquid according to claim 1, characterized in that: The anti-sticking agent includes talcum powder, magnesium stearate or micro powder silica gel.

3. The medicinal sustained-release antistatic coating liquid according to claim 1, characterized in that: The plasticizer includes dibutyl phthalate, triethyl citrate or polyethylene glycol.

4. The medicinal sustained-release antistatic coating liquid according to claim 1, characterized in that: The long-chain saturated fatty acid is selected from lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid or behenic acid, and the long-chain saturated fatty acid glyceride is selected from monoglyceride, diglyceride or triglyceride formed by condensation of any one of the above long-chain saturated fatty acids with glycerol.

5. The medicinal sustained-release antistatic coating liquid according to claim 1, characterized in that: The concentration of the ethanol aqueous solution is 80% to 95%.

6. The method for preparing the medicinal sustained-release antistatic coating solution according to any one of claims 1 to 5, characterized in that: The following steps are involved: Take ethanol or ethanol water solution, add the prescribed amount of ethyl cellulose, and fully dissolve it to obtain an ethyl cellulose solution; weigh the prescribed amount of lubricant, dissolve it in ethanol and then add it to the ethyl cellulose solution, mix well to obtain a mixed solution, add the prescribed amount of plasticizer and anti-sticking agent to the mixed solution in turn, and mix well to obtain the medicinal sustained-release antistatic coating solution.

7. An enteric-coated sustained-release drug particle, characterized in that: The structure comprises drug-loaded particles, a sustained-release coating and an enteric coating arranged in sequence from the inside to the outside, wherein the sustained-release coating is prepared from the medicinal sustained-release antistatic coating liquid described in any one of claims 1-5.

8. The enteric-coated sustained-release drug particles according to claim 7, characterized in that: The particle size of the enteric-coated sustained-release drug particles is in the range of 50 to 350 μm, and the active ingredient of the drug-loaded particles is tamsulosin hydrochloride.

9. The enteric-coated sustained-release drug particles according to claim 7, characterized in that: The enteric coating is prepared from an enteric coating liquid containing an enteric coating material, a plasticizer and an anti-adhesive agent. The enteric coating material is a copolymer of methacrylic acid and ethyl acrylate.

10. A tamsulosin hydrochloride orodisintegrating tablet, characterized in that: Comprising the enteric-coated sustained-release drug particles according to claim 8.

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