Estradiol valerate film-coated tablet and preparation method thereof

Abstract

The invention belongs to the technical field of medicines, and relates to an estradiol valerate film-coated tablet and a preparation method thereof. The estradiol valerate sugar film-coated tablet comprises the following components in percentage by mass: 60%-80% of an estradiol valerate tablet core and 20%-40% of a water-based sugar film coating, the water-based sugar film coating comprises a powder coating layer and a coloring layer. The preparation method of the estradiol valerate film-coated tablet comprises the following steps: preheating the estradiol valerate tablet core; coating with a powder coating layer; drying the coated tablet of the estradiol valerate powder coating layer; coating a coloring layer; and drying and cooling the estradiol valerate coloring layer coated tablet to obtain the estradiol valerate sugar film coated tablet. According to the estradiol valerate sugar film-coated tablet and the preparation method thereof provided by the invention, the coating process is simple and efficient, and the stability of related substances of a preparation can be ensured while the process is optimized.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to an estradiol valerate sugar film-coated tablet and a preparation method thereof. Background Art

[0002] Estradiol valerate tablets are used in combination with progestins to establish an artificial menstrual cycle to supplement estrogen deficiency mainly associated with natural or artificial menopause; vasomotor diseases (such as hot flashes), genitourinary tract nutritional diseases (such as vulvovaginal atrophy, dyspareunia, urinary incontinence) and psychiatric diseases (such as sleep disorders, asthenia).

[0003] In the prior art, the reference preparation, such as batch number 784A from DELPHARM Lille SAS, is a sugar-coated tablet. Its preparation process is complex, labor-intensive, takes 8-10 hours in total, requires multiple drying steps, relies on manual experience, and is prone to mottling, cracking, and discoloration.

[0004] Chinese patent document CN 119385963 A discloses an estradiol valerate sugar-coated tablet and its preparation method, comprising five layers of coating: a powder coating layer, a first sugar coating layer, a coloring layer, a second sugar coating layer, and a polishing layer. The preparation method involves evenly dripping a coating suspension onto the tablet core, and then repeatedly homogenizing and drying to achieve the purpose of coating weight gain. This process is cumbersome, requiring the operator to constantly switch on and off the spraying and heating procedures of the coating pot, and also relying on manual experience to determine the homogenization and drying time, which is not conducive to industrial production. Furthermore, the S2 coating in the document has a weight gain of 64-68wt%, the S3 coating has a weight gain of approximately 2-4wt%, the S4 coating has a weight gain of 2-4wt%, and the S5 coating has a weight gain of 1-3wt%. The document has a large number of coating layers and a complex process. Summary of the Invention

[0005] The purpose of the present invention is to provide an estradiol valerate sugar film-coated tablet and a preparation method thereof, wherein the coating process is simple and efficient, and the stability of related substances in the preparation can be ensured while optimizing the process.

[0006] In order to solve the above technical problems, the present invention provides an estradiol valerate sugar film-coated tablet and a preparation method thereof as follows:

[0007] An estradiol valerate sugar film-coated tablet comprises: a core of estradiol valerate with a mass percentage of 60%-80% and an aqueous sugar film coating with a mass percentage of 20%-40%; the aqueous sugar film coating comprises: a powder coating layer and a coloring layer.

[0008] Optionally, the powder coating layer comprises 40%-60% by mass of sucrose and 40%-60% by mass of a film coating premix 1, wherein the film coating premix 1 is 290G690001-CN.

[0009] Optionally, the coloring layer is made of a film coating premix 2, and the film coating premix 2 is 03K620009-CN.

[0010] Optionally, the estradiol valerate tablet core is prepared from estradiol valerate, lactose, corn starch, povidone K25, talc and magnesium stearate.

[0011] A method for preparing estradiol valerate sugar film-coated tablets comprises the following steps: preheating the estradiol valerate tablet cores: adding the estradiol valerate tablet cores into a high-efficiency coating machine for preheating;

[0012] Powder coating: adding a pre-prepared powder coating solution to coat the preheated estradiol valerate tablet core to obtain estradiol valerate powder coating layer coated tablets;

[0013] The estradiol valerate powder coating layer coated tablets are dried to obtain estradiol valerate powder coating layer coated tablets having a powder coating layer weight gain of 30%-60% of the estradiol valerate core tablets;

[0014] Coloring layer coating: adding a pre-made coloring layer coating solution to coat the estradiol valerate powder coating layer tablets with a powder coating layer weight gain of 30%-60% of the estradiol valerate core tablet to obtain estradiol valerate coloring layer coated tablets;

[0015] The estradiol valerate colored layer coated tablets are dried and cooled to obtain estradiol valerate sugar film coated tablets whose colored layer weight gain is 1%-3% of that of the estradiol valerate powder coating layer coated tablets.

[0016] Optionally, the estradiol valerate tablet core is preheated and the estradiol valerate powder coating layer is coated on the tablet. The air inlet temperature of the high-efficiency coating machine is 50-70°C, the coating pan speed is 6 rpm, and the preheating ends when the material temperature exceeds 37.0°C.

[0017] Optionally, for the powder coating layer coating, the air inlet temperature of the high-efficiency coating machine is 50-70°C, the main engine speed is 6-20rpm, the peristaltic pump speed is 10-25ml / min, the spray gun pressure is 0.1-0.3MPa, and the atomization pressure is 0.1-0.3MPa. The tablet bed temperature is maintained at 35.0-50.0°C during the coating process to obtain estradiol valerate powder coating layer coated tablets.

[0018] Optionally, the estradiol valerate powder coating layer coated tablets are dried and cooled, with the air inlet temperature of the high-efficiency coating machine at 50-70° C. and the main machine speed at 6-20 rpm, and dried for 1-5 minutes, followed by cooling after drying, to obtain estradiol valerate powder coating layer coated tablets having a powder coating layer weight gain of 30%-60% of the estradiol valerate core tablets;

[0019] Optionally, for the coloring layer coating, the air inlet temperature of the high-speed coating machine is 50-70°C, the main engine speed is 6-20rpm, the peristaltic pump speed is 10-25ml / min, the spray gun pressure is 0.1-0.3MPa, and the atomization pressure is 0.1-0.3MPa. The tablet bed temperature is maintained at 35.0-50.0°C during the coating process to obtain estradiol valerate coloring layer coated tablets.

[0020] The estradiol valerate colored layer coated tablets are dried and cooled, and the air inlet temperature of the high-efficiency coating machine is 50-70°C and the main machine speed is 6-20rpm. The drying is performed for 1-5 minutes, and the tablets are cooled after drying to obtain estradiol valerate sugar film-coated tablets whose colored layer weight gain is 1%-3% of the estradiol valerate powder coating layer coated tablets.

[0021] Optionally, the entire preparation method takes 3 to 5 hours.

[0022] The present invention has the following beneficial effects:

[0023] The sugar film coating of the present invention comprises only a powder coating layer and a coloring layer, and the sugar film coating accounts for 30% to 60% of the mass of the estradiol valerate tablet core. Experiments have shown that the properties, related substances, solubility, and content of the estradiol valerate sugar film-coated tablets of the present invention do not change significantly under high temperature conditions, while the solubility of the reference preparation (sugar-coated tablets) shows a decreasing trend (91.5% to 82.5%). The estradiol valerate sugar film-coated tablets are relatively stable under high temperature conditions.

[0024] The estradiol valerate sugar film-coated tablets of the present invention are placed under high humidity (25° C., 75% RH) conditions for 30 days. The moisture absorption and weight gain of the estradiol valerate sugar film-coated tablets meet the requirements, and the properties, related substances, solubility and content do not change significantly.

[0025] The properties, related substances, solubility and content of the estradiol valerate sugar film-coated tablets of the present invention do not change significantly under high temperature (60° C.), indicating that the estradiol valerate sugar film-coated tablets of the present invention are relatively stable under high temperature conditions.

[0026] Under light conditions, the properties, related substances, solubility and content of estradiol valerate film-coated tablets did not change significantly; therefore, estradiol valerate film-coated tablets were relatively stable under light conditions.

[0027] Experiments have shown that the estradiol valerate sugar film-coated tablet preparation of the present invention has good stability.

[0028] The sugar film coating of the present invention is simplified into two stages: powder coating and coloring layer coating. A fully perforated coating pan is used. The entire process only takes 3-5 hours, and the process parameters can be standardized.

[0029] The present invention optimizes the sugar-coated tablets into sugar film-coated tablets. Compared with the prior art, the sugar film-coated tablets are stable during storage, have a simple preparation process, low production cost, and are suitable for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 This is a dissolution curve of estradiol valerate sugar film-coated tablets prepared in Example 2 of the present invention in a water + 0.3% sodium lauryl sulfate medium;

[0031] Figure 2 This is a dissolution curve of the estradiol valerate sugar film-coated tablets prepared in Example 3 of the present invention in a water + 0.3% sodium lauryl sulfate medium. DETAILED DESCRIPTION

[0032] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail in the following examples. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0033] Example 1

[0034] In this example, when the weight gain of the powder coating layer is 50%, the coating effects of sucrose: film coating premix 1 = 4:6; sucrose: film coating premix 1 = 5:5; and sucrose: film coating premix 1 = 6:4 are investigated.

[0035] 1.1 Prescribing Information

[0036] Tablet prescription information is shown in Table 1

[0037] Table 1

[0038]

[0039] ②Coating layer prescription information, Table 2

[0040] Table 2

[0041]

[0042] Note: The powder coating layer dosage is calculated based on 100% weight gain of the tablet core, and the coloring layer dosage is calculated based on 3% weight gain of the powder coating layer coated tablet.

[0043] 1.2 Preparation process

[0044] ① Weighing: Weigh the prescribed amount of lactose, corn starch, povidone K25, and estradiol valerate API;

[0045] ② Prepare the adhesive: prepare povidone K25 into an 18.75% aqueous solution, with the amount of the adhesive accounting for 21% of the prescription amount, as shown in Table 3.

[0046] Table 3

[0047] Excipient name Prescription amount / g Povidone K25 60.00 purified water 260.00 Gross weight 320.00

[0048] ③ Premixing in a wet granulator: Sieve lactose, corn starch and estradiol valerate API together and place in a wet granulator and mix for 10 minutes.

[0049] ④ Granulation: Add the prescribed amount of binder and granulate.

[0050] ⑤ Wet granulation: pass through a 20-mesh sieve for wet granulation.

[0051] ⑥ Drying: Place in a fluidized bed for drying.

[0052] ⑦ Total mixing: Weigh the dried granules, add the corresponding amount of talc and magnesium stearate after conversion, and mix in a universal mixer for 10 minutes.

[0053] ⑧ Tablet compression: Theoretical tablet weight is 80 mg. Use a 6.0 mm round shallow concave punch to compress the tablets. The tablet weight control range is ±7.5%, and the friability is ≤1.0%.

[0054] ⑨Coating:

[0055] ⑴Powder coating:

[0056] a. Prepare the coating solution. The coating solution prescription is shown in Table 4.

[0057] Table 4

[0058] prescription Prescription 1 Prescription 2 Prescription 3 batch number 231210BY01 231210BY01 231210BY01 Sucrose: Film coating premix 1 4:6 5:5 6:4 Sucrose / g 160 200 240 Film coating premix 1 / g 240 200 160 Purified water / g 600 600 600 Total weight / g 1000 1000 1000

[0059] Weigh the prescribed amount of purified water and add it to a clean container. Start stirring. Then evenly add the prescribed amount of sucrose and film coating premix 1. Continue stirring during the addition process for at least 1 hour. Set aside.

[0060] b. Coating process. Coating parameters are shown in Table 5.

[0061] Table 5

[0062]

[0063] Preheating: Place the tablet cores into a high-efficiency coating machine for preheating. Set the inlet air temperature to 50-70°C and the pan speed to 6 rpm. Preheating ends when the material temperature exceeds 37.0°C. After preheating, sample 100 tablets and weigh them to determine the initial tablet weight.

[0064] Spray coating: Set the inlet air temperature (50-70°C), main engine speed (6-20 rpm), peristaltic pump speed (10-25 ml / min), spray gun pressure (0.1-0.3 MPa), and atomizer pressure (0.1-0.3 MPa) for spray coating. Maintain the tablet bed temperature at 35.0-50.0°C during the coating process. Adjust parameters according to material conditions during production. The inlet air temperature must be adjusted within this range. Samples should be collected at least every 20 minutes during the spraying process to monitor coating weight gain.

[0065] Drying and Cooling: Set the air inlet temperature (50-70°C) and the machine speed (6-20 rpm) for 1-5 minutes. Determine the tablet weight of 100 tablets and calculate the coating weight gain. Calculate the coating weight gain as follows: (Weight of qualified coated tablets - Net weight of core tablets) ÷ Net weight of core tablets × 100%.

[0066] c. Coating weight gain, Table 6

[0067] Table 6

[0068] batch number Weight gain% 231210BY01 50 231210BY02 50 231210BY03 50

[0069] (2) Coloring layer coating

[0070] a. Prepare coating solution with a solid content of 15%. The coating solution formula is shown in Table 7.

[0071] Table 7

[0072] name Prescription amount / g Prescription amount / g Prescription amount / g batch number 231210BY0101 231210BY0201 231210BY0201 Film coating premix 2 25.0 25.0 25.0 purified water 141.7 141.7 141.7 Gross weight 166.7 166.7 166.7

[0073] Weigh the prescribed amount of purified water into a clean container, start stirring, and then evenly add the prescribed amount of film coating premix 2. Continue stirring during the addition process for at least 1 hour and set aside.

[0074] b. Coating process. Coating parameters are shown in Table 8.

[0075] Table 8

[0076]

[0077] Spray coating: Set the inlet air temperature to 50-70°C, the main machine speed to 6-20 rpm, the peristaltic pump speed to 10-25 ml / min, the spray gun pressure to 0.1-0.3 MPa, and the atomizer pressure to 0.1-0.3 MPa for spray coating. Maintain the tablet bed temperature at 35.0-50.0°C during the coating process. Adjust parameters according to the material state during production. The inlet air temperature must be adjusted within the specified range. Samples should be collected at least every 20 minutes during the spraying process to monitor coating weight gain.

[0078] Drying and Cooling: Set the air inlet temperature (50-70°C) and the machine speed (6-20 rpm) for 1-5 minutes. After drying, turn off the heat. After cooling, weigh 100 tablets and calculate the coating weight gain. Calculate coating weight gain as follows: (Weight of qualified coated tablets - Net weight of core tablets) ÷ Net weight of core tablets × 100%.

[0079] c. Coating weight gain, as shown in Table 9.

[0080] Table 9

[0081] batch number Weight gain% 231210BY0101 2 231210BY0201 2 231210BY0301 2

[0082] 1.3 Experimental Results

[0083] Batches 231210BY0101, 231210BY0201, and 231210BY0301 have a delicate surface and uniform and rich color.

[0084] Example 2

[0085] In this embodiment, the mass ratio of sucrose in the powder coating layer to the film coating premix 1 is 4:6, that is, the mass ratio of sucrose to the film coating premix 1 is 40%:60%, and the weight gain of the powder coating layer is 50%, 40% and 60% respectively.

[0086] The preparation method of estradiol valerate sugar film-coated tablets is as follows:

[0087] 2.1 Prescribing Information

[0088] ① Tablet prescription information, as shown in Table 10.

[0089] Table 10

[0090]

[0091]

[0092] ②Prescription information of coating layer is shown in Table 11.

[0093] Table 11

[0094]

[0095] Note: The powder coating layer dosage is calculated based on 100% weight gain of the tablet core, and the coloring layer dosage is calculated based on 3% weight gain of the powder coating layer coated tablet.

[0096] 2.2 Preparation process

[0097] ① Weighing: Weigh the prescribed amount of lactose, corn starch, povidone K25, and estradiol valerate API;

[0098] ② Prepare the adhesive: prepare povidone K25 into an 18.75% aqueous solution. The amount of adhesive used accounts for 21% of the prescription amount. The amount of adhesive used is shown in Table 12.

[0099] Table 12

[0100] Excipient name Prescription amount / g Povidone K25 60.00 purified water 260.00 Gross weight 320.00

[0101] ③ Premixing in a wet granulator: Sieve lactose, corn starch and API together and place in a wet granulator and mix for 10 minutes.

[0102] ④ Granulation: Add the prescribed amount of binder and granulate.

[0103] ⑤ Wet granulation: pass through a 20-mesh sieve for wet granulation.

[0104] ⑥ Drying: Place in a fluidized bed for drying.

[0105] ⑦ Total mixing: Weigh the dried granules, add the corresponding amount of talc and magnesium stearate after conversion, and mix in a universal mixer for 10 minutes.

[0106] ⑧ Tablet compression: Theoretical tablet weight 80 mg, 6.0 mm round shallow concave punch tableting, tablet weight control range ± 7.5%, friability ≤ 1.0%.

[0107] ⑨Coating:

[0108] ⑵Powder coating:

[0109] a. Prepare coating solution with a solid content of 40%. The coating solution formula is shown in Table 13.

[0110] Table 13

[0111] name Prescription amount / g sucrose 640 Film coating premix 1 960 purified water 2400 Gross weight 4000

[0112] b. Coating parameters

[0113]

[0114] c. Coating weight gain, as shown in Table 14

[0115] Table 14

[0116] batch number Weight gain% 231225BY01 40 231225BY02 50 231225BY03 60

[0117] The coating weight gain calculation method is the same as in Example 1.

[0118] (2) Coloring layer coating

[0119] a. Prepare coating solution with a solid content of 15%. The coating solution formula is shown in Table 15.

[0120] Table 15

[0121]

[0122]

[0123] b. Coating parameters, as shown in Table 16.

[0124] Table 16

[0125]

[0126] c. Coating weight gain: The coating weight gain calculation method is the same as that in Example 1. The coating weight gain is shown in Table 17.

[0127] Table 17

[0128] batch number Weight gain% 231225BY0101 2 231225BY0201 2 231225BY0301 2

[0129] 2.3 Experimental Results

[0130] 2.3.1 Dissolution test

[0131] Assay: 231225BY0101, 231225BY0201, 231225BY0301, and tablet cores (lot number 231225SP01) were incubated in water + 0.3% sodium lauryl sulfate using a basket method at 100 rpm. Samples were taken at 5, 10, 15, 20, 30, 45, and 60 minutes, and the cumulative dissolution rate was measured. The test results are shown in Table 18:

[0132] Table 18

[0133]

[0134]

[0135] The dissolution curve of water + 0.3% sodium lauryl sulfate medium is as follows: Figure 1 shown.

[0136] The test results showed that the dissolution of batch 231225BY0201 was similar to that of the reference preparation.

[0137] 2.3.2 Stability test

[0138] In accordance with the "Basic Technical Guidelines for Research on Chemical Drug Preparations" and the 2020 edition of the Chinese Pharmacopoeia, Part IV, General Chapter 9001, Guidelines for Stability Testing of Active Pharmaceutical Ingredients and Preparations, the stability of estradiol valerate film-coated tablets under various environmental factors (such as temperature, humidity, light exposure, etc.) was investigated, and whether the relevant indicators of estradiol valerate film-coated tablets met the requirements of the quality standards was investigated.

[0139] ① Storage conditions and time, as shown in Table 19.

[0140] Table 19

[0141]

[0142] ② Results of influencing factors

[0143] a. Properties, as shown in Table 20

[0144] Table 20

[0145]

[0146]

[0147] b. Related substances, Table 21

[0148] Table 21

[0149]

[0150]

[0151] Note: When the relevant substance is less than 0.1%, it is not included in the total impurities.

[0152] c. Dissolution determination, Table 22.

[0153] Table 22

[0154]

[0155] d content determination, Table 23

[0156] Table 23

[0157]

[0158]

[0159] eWeight gain by moisture absorption, Table 24.

[0160] Table 24

[0161]

[0162] fResult analysis and conclusion

[0163] Under high temperature conditions, the properties, related substances, solubility and content of estradiol valerate film-coated tablets did not change significantly, while the solubility of the reference preparation showed a decreasing trend (91.5% to 82.5%). Estradiol valerate film-coated tablets are relatively stable under high temperature conditions.

[0164] After 30 days of storage under high humidity (25°C, 92.5% RH), mold was observed on the estradiol valerate sugar film-coated tablets and the reference preparation, indicating significant changes in their properties. No further testing was performed, and high humidity (25°C, 75% RH) conditions were initiated. After 30 days of storage under high humidity (25°C, 75% RH), the moisture absorption and weight gain of the estradiol valerate sugar film-coated tablets and the reference preparation met the requirements, with no significant changes in properties, related substances, solubility, or content. Both the estradiol valerate sugar film-coated tablets and the reference preparation remained relatively stable under high humidity (25°C, 75% RH) conditions.

[0165] Under light conditions, there was no significant change in the properties, related substances, solubility and content of estradiol valerate film-coated tablets and reference preparations; therefore, estradiol valerate film-coated tablets and reference preparations should be light-stable during use and storage.

[0166] In conclusion, the stability of estradiol valerate sugar film-coated tablet preparation is good.

[0167] Example 3

[0168] When the coating weight gain was 50%, the dissolution curves of the tablets were examined when the solid content of the powder coating layer was 30%, 40%, and 50%.

[0169] Sucrose: film coating premix 1 = 4:6.

[0170] Preparation method: Add the weighed purified water into a clean container, start stirring, then evenly add the prescribed amount of sucrose and film coating premix 1, stirring continuously during the addition process for at least 1 hour, and set aside.

[0171] The preparation method of estradiol valerate sugar film-coated tablets is as follows:

[0172] 3.1 Prescribing Information

[0173] ① Tablet prescription information, Table 25.

[0174] Table 25

[0175]

[0176] ②Prescription information for coating layer, Table 26.

[0177] Table 26

[0178]

[0179] Note: The powder coating layer prescription is calculated based on 100% weight gain, and the coloring layer prescription is calculated based on 3% weight gain.

[0180] 3.2 Preparation process

[0181] ① Weighing: Weigh the prescribed amount of lactose, corn starch, povidone K25, and estradiol valerate API;

[0182] ② Prepare the adhesive: Prepare povidone K25 into an 18.75% aqueous solution. The amount of adhesive used accounts for 21% of the prescription amount, as shown in Table 27.

[0183] Table 27

[0184] Excipient name Prescription amount / g Povidone K25 60.00 purified water 260.00 Gross weight 320.00

[0185] ③ Premixing in a wet granulator: Sieve lactose, corn starch and API together and place in a wet granulator and mix for 10 minutes.

[0186] ④ Granulation: Add the prescribed amount of binder and granulate.

[0187] ⑤ Wet granulation: pass through a 20-mesh sieve for wet granulation.

[0188] ⑥ Drying: Place in a fluidized bed for drying.

[0189] ⑦ Total mixing: Weigh the dried granules, add the corresponding amount of talc and magnesium stearate after conversion, and mix in a universal mixer for 10 minutes.

[0190] ⑧ Tablet compression: Theoretical tablet weight 80 mg, 6.0 mm round shallow concave punch tableting, tablet weight control range ± 7.5%, friability ≤ 1.0%.

[0191] ⑨Coating:

[0192] ⑶Powder coating:

[0193] a. Prepare the coating solution. The coating solution prescription is shown in Table 28.

[0194] Table 28

[0195]

[0196]

[0197] b. Coating parameters, Table 29.

[0198] Table 29

[0199]

[0200] c. Coating weight gain, Table 30.

[0201] Table 30

[0202] Color coating

[0203] a. Prepare coating solution with a solid content of 15%. The coating solution formula is shown in Table 30.

[0204] Table 30

[0205] batch number Weight gain% 231216BY01 50 231216BY02 50 231216BY03 50

[0206] name Prescription amount / g Prescription amount / g Prescription amount / g batch number 231225BY0101 231225BY0201 231225BY0201 Film coating premix 2 25.0 25.0 25.0 purified water 141.7 141.7 141.7 Gross weight 166.7 166.7 166.7

[0207] b. Coating parameters, as shown in Table 16.

[0208] Table 16

[0209]

[0210] c. Coating weight gain: The coating weight gain calculation method is the same as that in Example 1. The coating weight gain is shown in Table 17.

[0211] Table 17

[0212] batch number Weight gain% 231216BY0101 2 231216BY0201 2 231216BY0301 2

[0213] 3.3 Experimental Results

[0214] 3.3.1 Dissolution test

[0215] Determination method: Take 231216BY01, 231216BY02, and 231216BY03 in water + 0.3% sodium lauryl sulfate as the medium, use the basket method at 100 rpm, and take samples at 5, 10, 15, 20, 30, 45, and 60 minutes to measure the cumulative dissolution amount. The test results are shown in Table 31:

[0216] Table 31

[0217]

[0218] The dissolution curve of water + 0.3% sodium lauryl sulfate medium is as follows: Figure 2 shown.

[0219] The experimental results show that when the coating weight gain is 50% and the solid content of the powder coating layer is 30%-50%, the dissolution curve is similar to that of the reference preparation.

[0220] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. An estradiol valerate sugar film-coated tablet, characterized in that: include: A core tablet containing 60% to 80% by mass of estradiol valerate and a film coating containing 20% ​​to 40% by mass of aqueous sugar; The aqueous sugar film coating comprises a powder coating layer and a coloring layer.

2. The estradiol valerate sugar film-coated tablet according to claim 1, characterized in that The powder coating layer includes 40%-60% by mass of sucrose and 40%-60% by mass of a film coating premix 1. The film coating premix 1 is 290G690001-CN.

3. The estradiol valerate sugar film-coated tablet according to claim 1, characterized in that The colored layer is made of a film coating premix 2, which is 03K620009-CN.

4. The estradiol valerate sugar film-coated tablet according to claim 1, characterized in that The estradiol valerate tablet core is prepared from estradiol valerate, lactose, corn starch, povidone K25, talc and magnesium stearate.

5. The method for preparing the estradiol valerate sugar film-coated tablets according to claims 1 to 4, characterized in that: The method comprises the following steps: preheating the estradiol valerate tablet core: adding the estradiol valerate tablet core into a high-efficiency coating machine for preheating; Powder coating: adding a pre-prepared powder coating solution to coat the preheated estradiol valerate tablet core to obtain estradiol valerate powder coating layer coated tablets; The estradiol valerate powder coating layer coated tablets are dried to obtain estradiol valerate powder coating layer coated tablets having a powder coating layer weight gain of 30%-60% of the estradiol valerate core tablets; Coloring layer coating: adding a pre-made coloring layer coating solution to coat the estradiol valerate powder coating layer tablets with a powder coating layer weight gain of 30%-60% of the estradiol valerate core tablet to obtain estradiol valerate coloring layer coated tablets; The estradiol valerate colored layer coated tablets are dried and cooled to obtain estradiol valerate sugar film coated tablets whose colored layer weight gain is 1%-3% of that of the estradiol valerate powder coating layer coated tablets.

6. The method for preparing the estradiol valerate sugar film-coated tablet according to claim 5, characterized in that: The estradiol valerate tablet core is preheated and the estradiol valerate powder coating layer is coated on the tablet. The air inlet temperature of the high-efficiency coating machine is 50-70°C, the coating pan speed is 6 rpm, and the preheating ends when the material temperature exceeds 37.0°C.

7. The method for preparing the estradiol valerate sugar film-coated tablet according to claim 5, characterized in that: For the powder coating layer coating, the high-efficiency coating machine has an air inlet temperature of 50-70°C, a main engine speed of 6-20rpm, a peristaltic pump speed of 10-25ml / min, a spray gun pressure of 0.1-0.3MPa, and an atomization pressure of 0.1-0.3MPa. During the coating process, the tablet bed temperature is maintained at 35.0-50.0°C to obtain estradiol valerate powder coating layer coated tablets.

8. The method for preparing the estradiol valerate sugar film-coated tablets according to claim 5, characterized in that: The estradiol valerate powder coating layer coated tablets are dried in a high-efficiency coating machine at an inlet air temperature of 50-70°C and a main machine speed of 6-20 rpm for 1-5 minutes to obtain estradiol valerate powder coating layer coated tablets having a powder coating layer weight gain of 30%-60% of the estradiol valerate core tablets; The estradiol valerate colored layer coated tablets are dried and cooled, and the air inlet temperature of the high-efficiency coating machine is 50-70°C and the main machine speed is 6-20rpm. The drying is performed for 1-5 minutes, and the tablets are cooled after drying to obtain estradiol valerate sugar film-coated tablets whose colored layer weight gain is 1%-3% of the estradiol valerate powder coating layer coated tablets.

9. The method for preparing the estradiol valerate sugar film-coated tablet according to claim 5, characterized in that: For the coloring layer coating, the high-speed coating machine has an air inlet temperature of 50-70°C, a main machine speed of 6-20rpm, a peristaltic pump speed of 10-25ml / min, a spray gun pressure of 0.1-0.3MPa, and an atomization pressure of 0.1-0.3MPa. The tablet bed temperature is maintained at 35.0-50.0°C during the coating process to obtain estradiol valerate coloring layer coated tablets.

10. The method for preparing estradiol valerate sugar film-coated tablets according to any one of claims 5 to 9, characterized in that: The entire preparation process takes 3 to 5 hours.

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