Oxagolide sodium pellet and preparation method thereof

Abstract

The invention discloses an oxaggolil sodium pellet. The pellet is composed of a pellet core and a coating layer wrapping the pellet core, the pellet core is prepared from the following components in percentage by mass: 95 to 99 percent of oxaggolil sodium, 0.5 to 2.5 percent of adhesive and 0.5 to 2.5 percent of pH (Potential of Hydrogen) regulator. The invention discloses a preparation method of the oxaggolil sodium pellet, which comprises the following steps: preparing a mother nucleus and a pellet core by adopting a centrifugal granulation method, drying the pellet core, and coating the dried pellet core to obtain the oxaggolil sodium pellet. The oxaggolil sodium pellet disclosed by the invention is high in true sphericity, uniform in particle size distribution and high in drug loading capacity, and the drug loading capacity of the pellet core is greater than or equal to 95%.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical science and mainly relates to an oxaragoline sodium microgranule and its preparation method. Background Technology

[0002] Elagolix Sodium is an oral, short-acting gonadotropin-releasing hormone (GnRH) antagonist. It works by competing with endogenous GnRH for receptors on pituitary cells, rapidly inhibiting the pituitary-gonadal axis, blocking endogenous LH and FSH, thereby reducing hormone secretion and achieving the goal of treating endometriosis.

[0003] Olagoglide sodium is a low-melting-point, amorphous, non-peptide small molecule that is highly soluble in water (solubility approximately 270 mg / mL) and has a bitter taste. The drug is unstable under humid and hot conditions and readily degrades to form compounds with a lactam structure (impurity A) and degradation impurities (impurity B). AbbVie's Chinese patent application CN111698992A discloses a pharmaceutical formulation for treating endometriosis, uterine fibroids, polycystic ovary syndrome, or adenomyosis. To overcome the tendency of oxaglide sodium to stick during tableting and gel during dissolution, the formulation uses a large amount of fillers (such as sodium carbonate, mannitol, and pregelatinized starch) in its preparation, resulting in an excessively large dosage form that is difficult for patients to swallow, especially with high-specification drug loading, which can easily lead to patient compliance problems. Chinese patent CN113876728A discloses an oxaglide lyophilized tablet, but its preparation method is complex, energy-intensive, and has a poor taste, making it unsuitable for large-scale industrial production and patient use.

[0004]

[0005] Therefore, there is a need to improve drug formulations and provide a sodium oxagoguelin formulation that can avoid the use of large amounts of sodium carbonate, effectively overcome gelation, and achieve a high drug loading capacity. Summary of the Invention

[0006] The purpose of this invention is to address the shortcomings and deficiencies of existing technologies by providing a high-drug-loading sodium oxagoguesh microgranules and a method for their preparation.

[0007] The key to this invention is firstly utilizing the mechanical property of sodium oxaragoline, which has high polarity and readily forms liquid bridges upon contact with water, thereby promoting powder agglomeration. High-drug-loaded microspheres can be prepared by supplementing only with a pure aqueous solution containing a small amount of binder. Then, the microspheres are dried using a low-temperature fluidized bed drying process. Finally, depending on the clinical application, appropriate functional coating materials are selected to coat the obtained microspheres.

[0008] The objective of this invention is achieved through the following technical solution:

[0009] An oxaragoline sodium microsphere comprises a core and a coating layer encapsulating the core; wherein the core is made of the following components in mass fractions:

[0010] Oxalagricans sodium 95-99%

[0011] Adhesive 0.5-2.5%

[0012] pH adjuster 0.5–2.5%.

[0013] Furthermore, the adhesive is one or more of hydroxypropyl methylcellulose, hydroxypropyl cellulose, and polyvinylpyrrolidone, preferably hydroxypropyl methylcellulose or hydroxypropyl cellulose.

[0014] Furthermore, the pH adjuster is one or more of anhydrous sodium carbonate, anhydrous sodium phosphate, and meglumine, preferably anhydrous sodium carbonate or meglumine. Anhydrous sodium carbonate or meglumine can maintain the pH of the binder solution at 11 or higher, effectively improving the stability of the formulation and preventing a rapid increase in impurities during the subsequent drying process of the microspheres.

[0015] Furthermore, the mass ratio of the adhesive to the pH adjuster is 1:2 to 2:1, preferably 1:1 to 2:1.

[0016] Furthermore, the coating layer is obtained by coating the pellet core with a coating solution.

[0017] Furthermore, the solid content of the coating material in the coating solution is 10-30%.

[0018] The coating material contains one or more of the following: butyl methacrylate, dimethylamine ethyl methacrylate and methyl acrylate (1:2:1) copolymer, polyvinyl alcohol, and ethyl cellulose.

[0019] Specifically, the coating material is selected from commercially available products. Coating powder, Coating powder or Coating powder.

[0020] More specifically, the coating material is selected from... EPO, Film coating premix or E-7-19040 aqueous dispersion.

[0021] As a specific embodiment of the sodium oxagoguel microspheres described in this invention, the microspheres consist of a core and a coating layer encapsulating the core; wherein the core is made of the following components by mass fraction:

[0022] Oxalagricans sodium 96%

[0023] 2% adhesive

[0024] 2% pH adjuster;

[0025] or

[0026] Oxalagricans sodium 97%

[0027] Adhesive 1.5%

[0028] pH adjuster 1.5%;

[0029] or

[0030] Oxalagricans sodium 97%

[0031] Adhesive 1.0%

[0032] pH adjuster 2.0%;

[0033] or

[0034] Oxalagricans sodium 98.5%

[0035] 1% adhesive

[0036] pH adjuster 0.5%;

[0037] or

[0038] Oxalagricans 99%

[0039] Adhesive 0.5%

[0040] pH adjuster 0.5%.

[0041] This invention provides a method for preparing the oxagogue sodium microspheres, comprising: preparing a core and a pellet by centrifugal granulation; drying the pellet in a fluidized bed; and coating the dried pellet to obtain oxagogue sodium microspheres.

[0042] Specifically, a method for preparing the oxaragoline sodium microspheres includes the following steps:

[0043] Step A, Weighing: Take each component and weigh it according to the weight ratio;

[0044] Step B, Preparation of adhesive solution: Weigh purified water according to the mass ratio of sodium oxaragoline to water of 1:1 to 1:5; dissolve the adhesive and pH adjuster in water to prepare the adhesive solution;

[0045] Step C, Preparation of the core: Add about 1 / 5 to 1 / 3, preferably 1 / 4, of the total amount of oxagogline sodium to the pelleting machine, and spray in about 10 to 15% of the total amount of the binder solution to form the core;

[0046] Step D, Preparation of pellet cores: Add the parent nucleus to the pelletizing machine, spray in the remaining adhesive solution, and at the same time add the remaining sodium oxaragoline to the pelletizing machine so that the parent nucleus gradually accumulates and grows into pellet cores. Use a sieving method to screen the pellet cores.

[0047] Step E, Core Drying and Coating: The core is placed in a fluidized bed for drying, and then coated with a coating solution to obtain sodium oxagoguel microcapsules.

[0048] In step B, preferably, the mass ratio of sodium oxaragoline to water is 1:2 to 1:4.

[0049] In step C, the parameters of the pelleting machine are: fan frequency: 5-15Hz, turntable speed: 150-250rpm, and liquid supply speed: 15-30rpm.

[0050] In step D, the particle size of the pellet core is 40-60 mesh.

[0051] Furthermore, pellet cores with a particle size of 40-60 mesh are sieved using a 40-60 mesh standard sieve, and the length-to-diameter ratio of the pellet cores is 1.2:1 to 1:1.

[0052] The parameters of the pellet making machine are as follows: fan frequency: 5~25Hz, turntable speed: 150~400rpm, liquid supply speed: 15~30rpm, powder supply speed: 30~50Hz.

[0053] In step E, the pellet core is dried to a moisture content of ≤2%.

[0054] The drying process is fluidized bed drying. During drying, the parameters of the fluidized bed are: fan frequency: 5-30Hz, air inlet temperature: 35-55℃, and material temperature: 25-45℃.

[0055] The coating is a bottom spray coating. During coating, the parameters of the fluidized bed are: fan frequency: 5-30Hz, air inlet temperature: 35-55℃, material temperature: 25-45℃, atomization pressure: 0.10-0.25MPa, and liquid supply rate: 2-10rpm.

[0056] The theoretical weight gain from coating is 8-18%.

[0057] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0058] Compared with the solution loading method for preparing pellet cores, the present invention uses a dry centrifugal loading method, which not only improves production efficiency, but also achieves a high drug loading capacity in the pellet cores, overcoming the shortcomings of the solution loading method, such as low drug loading capacity, long loading time, and high loss.

[0059] The sodium oxagogueshone microspheres of this invention have high sphericity, uniform particle size distribution, and high drug loading (drug loading of the pellet core ≥ 95%).

[0060] The sodium oxagoguel microcapsules of this invention can be coated with appropriate functional coating materials according to different clinical applications. The coated drug-loaded microcapsules have good taste masking effect and good stability.

[0061] The production process of sodium oxaragoline microspheres in this invention is simple. Attached Figure Description

[0062] Figure 1 This is a microscope image of the sodium oxaragoline microspheres prepared in Example 1.

[0063] Figure 2 This is a microscope image of the sodium oxaragoline microspheres prepared in Example 2.

[0064] Figure 3 This is a microscope image of the sodium oxaragoline microspheres prepared in Example 3.

[0065] Figure 4 This is a microscope image of the sodium oxaragoline microspheres prepared in Example 4.

[0066] Figure 5 This is a microscope image of the sodium oxaragoline microspheres prepared in Example 5.

[0067] Figure 6 This is a microscope image of the sodium oxaragoline microspheres prepared in Example 6. Detailed Implementation

[0068] To make the technical solution of the present invention easier to understand, the technical solution of the present invention will be further described in detail below with reference to specific embodiments, but the embodiments of the present invention do not constitute a limitation on the scope of the present invention.

[0069] Manufacturing equipment used in the formulation: centrifugal pelleting machine (Chongqing Kexu Pharmaceutical Machinery Equipment Manufacturing Co., Ltd.), multi-functional fluidized bed (DPL-IIA, Chongqing Jinggong Pharmaceutical Machinery Co., Ltd.), image particle analysis system (BT1600, Dandong Baite Instrument Co., Ltd.), standard sample sieve.

[0070] Core quality evaluation indicators:

[0071] The aspect ratio (R), friability (F), and yield (Y) were used as evaluation indicators for pellet cores.

[0072] in:

[0073] R = length of core diameter / length of core diameter.

[0074] F = After weighing, place the pellet cores in the drum of the friability tester, set the drum speed to 25 rap / min, rotate for 5 minutes, sift out the fine powder, and calculate the ratio of the pellet core weight loss to the original weight.

[0075] Y = Target pellet weight / Total material input.

[0076] Table 1. Material Usage Table

[0077]

[0078] Table 2. Process Parameters of Centrifugal Pelletizing Machine

[0079] Process Fan frequency (Hz) Rotary speed (rpm) Liquid supply rate (rpm) Powder supply rate (Hz) Nucleus preparation 10 200 20 0 Core preparation 20 350 25 35

[0080] Table 3. Parameter Table of Multifunctional Fluidized Bed Equipment

[0081] Work mode Fan frequency (Hz) Inlet air temperature (°C) Material temperature (°C) Boiling drying 20 40 30

[0082] Example 1

[0083] A method for preparing the core of oxaragoline sodium microspheres includes the following steps:

[0084] Step A, Weighing: Take each component and weigh it according to the amount in Table 1;

[0085] Step B, Prepare the adhesive solution: Weigh purified water according to the ratio of sodium oxagorli to water = 1:3 (w / w), dissolve hydroxypropyl methylcellulose (adhesive) and anhydrous sodium carbonate (pH adjuster) in purified water to obtain the adhesive solution for later use;

[0086] Step C, Preparation of the mother nucleus: Take about 1 / 4 of the total amount of oxagogline sodium and place it in a centrifugal pellet mill. According to the process parameters in Table 2, turn on the fan, turntable and liquid supply pump respectively, and spray about 10% of the total amount of binder solution into the oxagogline sodium. After the mother nucleus is formed, turn off the equipment and discharge the material.

[0087] Step D, Preparation of pellet cores: Take the above-mentioned mother nuclei and add them to a centrifugal pellet mill. According to the process parameters in Table 2, turn on the fan, turntable and liquid supply pump respectively, and spray in the remaining adhesive solution. At the same time as spraying in the adhesive solution, add the remaining sodium oxaragoline to the centrifugal pellet mill so that the mother nuclei gradually accumulate and grow into pellet cores. Turn off the equipment, discharge the material, and sieve the pellet cores with a 40-60 mesh standard sieve.

[0088] Step E, Core Drying: First, take cores and place them in a multi-functional fluidized bed. The parameters of the multi-functional fluidized bed equipment are shown in Table 3. Set the drying mode to boiling drying, turn on the fan, heat and make the cores boil. After they are fully dried (moisture content ≤ 2%), discharge them for later use.

[0089] The quality evaluation results of the pellet cores in Example 1 are shown in Table 4. Typical pellet core characteristics are shown in Table 4. Figure 1 It is evident that the pellet cores from Example 1 exhibit good sphericity and high yield, meeting the requirements of large-scale industrial production.

[0090] Table 4. Quality Evaluation of Pellet Cores

[0091] Evaluation indicators Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Aspect ratio (R) 1.02 1.03 1.02 1.03 1.02 1.03 Crispness (F) 0.3 0.5 0.4 0.3 0.5 0.5 Yield (Y) 0.91 0.89 0.88 0.86 0.85 0.88

[0092] Example 2

[0093] Following the preparation method of the oxaragoline sodium microsphere core in Example 1, only the amount of hydroxypropyl methylcellulose and anhydrous sodium carbonate was adjusted, while the rest was the same as in Example 1, and the core was prepared.

[0094] The quality evaluation results of the pellet cores in Example 2 are shown in Table 4. Typical pellet core characteristics are shown in Table 4. Figure 2 It is evident that the pellet cores from Example 2 exhibit good sphericity and high yield, meeting the requirements of large-scale industrial production.

[0095] Example 3

[0096] Following the preparation method of the oxaragoline sodium microsphere core in Example 1, only the amount of hydroxypropyl methylcellulose and anhydrous sodium carbonate was adjusted, while the rest was the same as in Example 1, and the core was prepared.

[0097] The quality evaluation results of the pellet cores in Example 3 are shown in Table 4. Typical pellet core characteristics are shown in Table 4. Figure 3 It is evident that the pellet cores of Example 3 exhibit good sphericity and high yield, meeting the requirements of large-scale industrial production.

[0098] Example 4

[0099] Referring to the preparation method of the oxagogue sodium microsphere core in Example 1, the binder was adjusted to hydroxypropyl cellulose and the pH adjuster to meglumine, and the amounts of hydroxypropyl cellulose and meglumine were adjusted. The rest was the same as in Example 1, and the core was prepared.

[0100] The quality evaluation results of the pellet cores in Example 4 are shown in Table 4. Typical pellet core characteristics are shown in Table 4. Figure 4 It is evident that the pellet cores in Example 4 exhibit good sphericity and high yield, meeting the requirements of large-scale industrial production.

[0101] Example 5

[0102] Referring to the preparation method of the oxagogue sodium microsphere core in Example 1, the binder was adjusted to hydroxypropyl cellulose and the pH adjuster to meglumine, and the amounts of hydroxypropyl cellulose and meglumine were adjusted. The rest was the same as in Example 1, and the core was prepared.

[0103] The quality evaluation results of the pellet cores in Example 5 are shown in Table 4. Typical pellet core characteristics are shown in Table 5. Figure 5 It is evident that the pellet cores of Example 5 exhibit good sphericity and high yield, meeting the requirements of large-scale industrial production.

[0104] Example 6

[0105] Referring to the preparation method of the oxagogue sodium microsphere core in Example 1, the binder was adjusted to hydroxypropyl cellulose and the pH adjuster to meglumine, and the amounts of hydroxypropyl cellulose and meglumine were adjusted. The rest was the same as in Example 1, and the core was prepared.

[0106] The quality evaluation results of the pellet cores in Example 6 are shown in Table 4. Typical pellet core characteristics are shown in Table 4. Figure 6 It is evident that the pellet cores of Example 6 exhibit good sphericity and high yield, meeting the requirements of large-scale industrial production.

[0107] Example 7

[0108] Preparation of coating solution: Take The gastric-soluble film coating premix (gastric-soluble-85F630048-CN, mainly containing polyvinyl alcohol) is prepared into a 10% (by solids content) coating solution with purified water, and the theoretical weight gain of the coating is 15%.

[0109] Coating: Take the dried pellet cores from Example 1 and place them in a multi-functional fluidized bed for coating. The parameters of the multi-functional fluidized bed equipment are shown in Table 5. Set the bottom spray coating mode, turn on the fan, heat and fluidize the pellet cores. When the pellet cores reach the set material temperature, turn on the liquid supply pump and spray the coating liquid until the theoretical weight gain is reached. Turn off the liquid supply and continue drying for 30 minutes. Turn off the heating and wait for the material to cool down to room temperature. Turn off the fan to obtain sodium oxaragoline pellets.

[0110] Table 5. Parameter Table of Multifunctional Fluidized Bed Equipment

[0111]

[0112] Example 8

[0113] Preparation of coating solution: Take commercially available... EPO (mainly a copolymer of butyl methacrylate, dimethylamine ethyl methacrylate and methyl acrylate (1:2:1)) is prepared into a 30% (by solids content) aqueous dispersion using purified water, which is the coating solution. The theoretical weight gain of the coating is 18%.

[0114] Coating: Take the dried pellet core from Example 1 and coat it according to the method in Example 7 to prepare oxaragoline sodium microspheres.

[0115] Example 9

[0116] Preparation of coating solution: Go to commercially available... E-7-19040 aqueous dispersion (mainly containing ethyl cellulose) was prepared into a 12.5% ​​(based on solid content) coating solution using purified water, with a theoretical weight gain of 8%.

[0117] Coating: Take the dried pellet core from Example 1 and coat it according to the method in Example 7 to prepare oxaragoline sodium microspheres.

[0118] Example 10

[0119] The dissolution rate of sodium oxagoguelin microspheres prepared in Examples 7, 8 and 9 was determined.

[0120] The oxagolin sodium microspheres obtained in Examples 7, 8, and 9 (equivalent to 200 mg of oxagolin sodium) were aliquoted into No. 2 capsules, and the dissolution rate was determined according to the method for determining dissolution and release (Chinese Pharmacopoeia 2025 Edition, Part IV, General Chapter 0931, Method II). The dissolution rate determination method is as follows: paddle method, dissolution medium: 900 mL (pH 1.2 hydrochloric acid, pH 4.5 acetate buffer, pH 6.8 phosphate buffer), medium temperature: 37.0℃±0.5℃, rotation speed: 50 rpm. Timing was started when the formulation came into contact with the dissolution medium, and samples were taken at 10, 15, 20, 30, 45, 60, and 90 min, respectively. The samples were filtered, and the drug concentration in the filtrate was determined by HPLC, and the dissolution rate was calculated.

[0121] Table 6. Cumulative release rate of samples in hydrochloric acid at pH 1.2 (n=6)

[0122] Time (min) Example 7 Example 8 Example 9 10 18.5±2.51 15.7±2.22 0 15 35.4±2.31 34.7±2.11 0 20 58.8±2.12 52.5±2.01 0 30 74.2±1.84 75.6±1.75 6.8±4.21 45 92.5±1.14 95.4±1.40 12.3±3.01 60 95.6±1.21 99.4±1.41 25.6±2.84 90 99.2±1.14 99.6±1.14 45.4±2.31

[0123] Table 7. Cumulative release of samples in pH 4.5 acetate buffer (n=6)

[0124] Time (min) Example 7 Example 8 Example 9 10 32.4±2.14 30.3±1.94 0 15 42.3±2.05 44.9±1.65 0 20 63.4±1.84 66.9±1.52 0 30 85.6±1.10 88.3±0.92 12.6±3.09 45 97.2±1.01 97.6±0.89 21.3±2.51 60 98.2±0.95 98.3±0.67 35.6±2.02 90 99.4±0.89 99.1±0.45 58.4±1.80

[0125] Table 8. Cumulative release of samples in pH 6.8 phosphate buffer (n = 6)

[0126] Time (min) Example 7 Example 8 Example 9 10 27.3±1.89 0 0 15 40.1±1.56 0 0 20 68.4±1.23 0 0 30 85.1±0.54 0 15.6±2.83 45 97.2±0.78 0 25.3±2.20 60 98.7±0.89 0 40.6±1.89 90 99.8±0.54 0 68.4±1.56

[0127] The cumulative dissolution (release rate) of the oxagolin sodium microspheres obtained in Examples 7, 8, and 9 in hydrochloric acid (pH 1.2), acetate buffer (pH 4.5), and phosphate buffer (pH 6.8) are shown in Tables 6, 7, and 8, respectively. It can be seen that the batch-to-batch dissolution differences of the oxagolin sodium microsphere samples in Examples 7-9 are small. This phenomenon fully reflects the typical characteristics of a multi-unit drug delivery system and effectively overcomes the gelation problem. Furthermore, depending on the choice of coating material, the oxagolin sodium microspheres exhibit different dissolution and release behaviors, which can provide feasibility for further drug delivery system design.

[0128] Example 11

[0129] Stability test

[0130] The sodium oxagogueshone microspheres obtained in Examples 7, 8 and 9 (equivalent to 200 mg of sodium oxagogueshone) were packaged in the same double aluminum material and placed at 40°C and 75% RH for 3 months. Samples were taken at 0 days and 3 months to detect related substances in the sodium oxagogueshone microspheres. The results are shown in Table 9.

[0131] Table 9. Results of Sample Stability Study

[0132]

[0133] As can be seen, the sodium oxagoguelin microspheres obtained in Examples 7-9 showed no significant change in impurities after being placed at 40°C and 75% RH for 3 months, indicating good stability.

[0134] Example 12

[0135] Taste masking effect: The taste masking effect was evaluated by taking the pellet core obtained in Example 1 and the oxagogue sodium micro pellets obtained in Example 7 (equivalent to 200 mg of oxagogue sodium).

[0136] Six healthy volunteers with normal taste were selected and trained. The bitterness grading system and evaluation method were established, with grades 1 (no bitterness or very low bitterness), 2 (slight bitterness), 3 (obvious bitterness), and 4 (intense bitterness). Coated microcapsules, uncoated microcapsules, and oxaglidium powder (equivalent to 200 mg of sodium oxagli) were placed on the same spot on the volunteers' tongues for 10 seconds, then spat out and rinsed their mouths. The volunteers tasted the samples at intervals of at least 15 minutes, and each volunteer's bitterness rating was recorded. The results are shown in Table 10.

[0137] Table 10. Results of the sample masking experiment

[0138] Sample type Level 1 Level 2 Level 3 Level 4 Sodium oxalagoguel powder 0 0 1 5 Maru Core 0 4 2 0 Micro pellets 6 0 0 0

[0139] It is evident that, compared to the raw drug, oxaragoline sodium after coating has a good taste-masking effect.

Claims

1. A sodium oxaragoline microsphere, characterized in that: The microspheres consist of a core and a coating layer encapsulating the core; wherein the core is made of the following components by mass fraction: Oxalagricans sodium 95-99% Adhesive 0.5-2.5% pH adjuster 0.5–2.5%.

2. The sodium oxaragoline microspheres according to claim 1, characterized in that: The adhesive is one or more of hydroxypropyl methylcellulose, hydroxypropyl cellulose, and povidone; the pH adjuster is one or more of anhydrous sodium carbonate, anhydrous sodium phosphate, and meglumine.

3. The sodium oxaragoline microspheres according to claim 1 or 2, characterized in that: The adhesive is hydroxypropyl methylcellulose or hydroxypropyl cellulose; the pH adjuster is anhydrous sodium carbonate or meglumine.

4. The sodium oxaragoline microspheres according to claim 1, characterized in that: The coating layer is obtained by coating the pellet core with a coating solution.

5. The sodium oxaragoline microspheres according to claim 4, characterized in that: The coating liquid contains 10-30% solid content of the coating material; the coating material contains one or more of the following: butyl methacrylate, dimethylamine ethyl methacrylate and methyl acrylate (1:2:1) copolymer, polyvinyl alcohol, and ethyl cellulose.

6. The sodium oxaragoline microspheres according to claim 4, characterized in that: The coating material is selected from commercially available products. Coating powder, Coating powder or Coating powder; preferably, the coating material is selected from... EPO, Film coating premix or E-7-19040 aqueous dispersion.

7. A method for preparing oxaragoline sodium microspheres according to claim 1, characterized in that: include: The core and pellet were prepared by centrifugal granulation. The pellet was dried and then coated to obtain sodium oxagoguel microspheres.

8. The method for preparing oxaragoline sodium microspheres according to claim 7, characterized in that: Includes the following steps: Step A, Weighing: Take each component and weigh it according to the weight ratio; Step B, Preparation of adhesive solution: Weigh purified water according to the mass ratio of sodium oxaragoline to water of 1:1 to 1:5, preferably 1:2 to 1:4; dissolve the adhesive and pH adjuster in water to prepare an adhesive solution; Step C, Preparation of the core: Add about 1 / 5 to 1 / 3, preferably 1 / 4, of the total amount of oxagogline sodium to the pelleting machine, and spray in about 10 to 15% of the total amount of the binder solution to form the core; Step D, Preparation of pellet cores: Add the parent nucleus to the pelletizing machine, spray in the remaining adhesive solution, and at the same time add the remaining sodium oxaragoline to the pelletizing machine so that the parent nucleus gradually accumulates and grows into pellet cores. Use a sieving method to screen the pellet cores. Step E, Core Drying and Coating: The core is placed in a fluidized bed for drying, and then coated with a coating solution to obtain sodium oxaragoline microcapsules.

9. The method for preparing oxaragoline sodium microspheres according to claim 8, characterized in that: In step C, the parameters of the pelleting machine are: fan frequency: 5-15Hz, turntable speed: 150-250rpm, liquid supply speed: 15-30rpm. In step D, the particle size of the pellet core is 40-60 mesh; the parameters of the pelleting machine are: fan frequency: 5-25Hz, turntable speed: 150-400rpm, liquid supply speed: 15-30rpm, powder supply speed: 30-50Hz. In step E, the drying is fluidized bed drying. During drying, the parameters of the fluidized bed are: fan frequency: 5-30Hz, inlet air temperature: 35-55℃, material temperature: 25-45℃. The coating is bottom spray coating. During coating, the parameters of the fluidized bed are: fan frequency: 5-30Hz, inlet air temperature: 35-55℃, material temperature: 25-45℃, atomization pressure: 0.10-0.25MPa, and liquid supply rate: 2-10rpm.

10. The method for preparing oxaragoline sodium microspheres according to claim 7 or 8, characterized in that: The theoretical weight gain from coating is 8-18%.

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