A method for stabilizing the particle size of a fine powder medicine
By suspending drug micropowder and lubricant together in a temperature- and humidity-controlled airflow for cyclone treatment after air jet pulverization, the problem of particle size growth caused by amorphous drug crystallization was solved, and the stability of drug particle size and yield were improved.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- SICHUAN PURITY PHARM CO LTD
- Filing Date
- 2023-10-18
- Publication Date
- 2026-06-23
AI Technical Summary
In existing technologies, drugs are prone to surface amorphization after being pulverized by airflow, leading to increased particle size, which affects the drug deposition effect in the lungs, and the drug loss is serious during the pulverization process.
The drug micropowder and lubricant are suspended together in a temperature- and humidity-controlled airflow, and then subjected to cyclone treatment to achieve amorphous crystallization, thereby stabilizing the drug particle size and reducing drug adhesion to the wall.
It effectively stabilizes drug particle size, reduces drug aggregation during storage, improves drug yield, and reduces drug loss.
Smart Images
Figure CN117398911B_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a method for stabilizing the particle size of micronized drugs. Background Technology
[0002] Inhaled drugs delivered to the lungs typically have strict requirements regarding particle size; only particles with a diameter between 1 and 5 μm can achieve good pulmonary deposition. For active pharmaceutical ingredients (APIs) obtained through chemical synthesis, crystallization, and purification, the particle size is usually larger, ranging from tens to hundreds of micrometers. These large-diameter drug particles are unsuitable for inhalation. The most common method in production is to reduce the particle size using air jet milling technology to obtain particles suitable for inhalation. However, due to the high energy of air jet milling, particles easily form amorphous surfaces during the milling process. These amorphous portions are highly unstable and easily transform into more stable crystalline forms during production and storage, leading to aggregation between adjacent particles. This increases the particle size, affecting drug deposition in the lungs and impacting drug quality.
[0003] Researchers have conducted numerous studies on stabilizing particle size after air jet milling, but the results have been unsatisfactory. A commonly used method is to control the amorphous transformation of small-diameter drug particles during storage by regulating the temperature and / or humidity after air jet milling, thereby reducing drug aggregation. For example, Katharina Brodka-Pfeiffer et al., in their paper "Conditioning Following Powder Micronization: Influence on Particle Growth of Salbutamol Sulfate," maintained the small-diameter stability of salbutamol after micronization by controlling the storage temperature and / or humidity. However, even under controlled temperature and humidity conditions, the particles still undergo amorphous transformation, making it difficult to avoid particle size growth after micronization. In addition, patent CN108135851B describes increasing the humidity within the air jet milling chamber using a humidifier to reduce the formation of amorphous components. However, in practical applications, increasing humidity can easily lead to increased particle adhesion and reduce the product yield of the milling process. Patent CN101896165B reduces drug particle size through anti-solvent high-pressure homogenization, followed by spray drying to remove the anti-solvent components. However, this method has significant drawbacks. First, the batch size of drugs processed by high-pressure homogenization is relatively low, and multiple homogenization cycles are time-consuming. Second, during the process of removing the anti-solvent using spray drying, almost all the drug is adsorbed onto the spray drying tower wall and cyclone separator, making it nearly impossible to collect the drug powder. Patent CN105188679B discloses a method for conditioning the state of micronized crystal particles by using a temperature- and humidity-controlled conditioning gas to convert amorphous components into crystals. However, the method provided by this patent only allows API to exist in a suspended state in the conditioning zone for 0.1-600 seconds, which is too short for API to complete proper crystal conversion. In addition, due to the small particle size and large specific surface area of inhaled drugs, drug particles are easily adsorbed onto the surface of the delivery pipeline during delivery, failing to form a true suspension state. Moreover, the larger the surface area of the delivery pipeline, the greater the drug loss.
[0004] Therefore, providing a method that can stabilize the particle size of micronized drugs and reduce drug loss has become a problem that urgently needs to be solved by those skilled in the art. Summary of the Invention
[0005] This invention discloses a method for stabilizing the particle size of micronized drugs, which solves the problem in the prior art that the surface of drugs is easily amorphous after air jet milling, and the particle size increase caused by particle aggregation during the amorphous crystallization process.
[0006] The technical solution adopted in this invention is as follows:
[0007] The present invention discloses a method for stabilizing the particle size of micronized drugs, comprising: suspending micronized drugs and a lubricant together in a temperature- and humidity-controlled airflow, wherein the micronized drugs undergo amorphous transformation into crystals in the suspended airflow, thereby stabilizing the drug particle size;
[0008] Preferably, the surface of the drug is amorphous.
[0009] In some embodiments of the present invention, the drug comprises a lung-delivered drug delivered via oral inhalation.
[0010] In some embodiments of the present invention, the drug includes a short-acting muscarinic receptor antagonist, a long-acting muscarinic receptor antagonist, a short-acting β2 receptor agonist, and a long-acting β2 receptor agonist;
[0011] The preferred formulations are salbutamol sulfate, levosalbutamol, glycopyrronium bromide, or tiotropium bromide.
[0012] In some embodiments of the present invention, the lubricant includes at least one of phospholipid porous microspheres, magnesium stearate, L-leucine, trileucine, and lactose.
[0013] In some embodiments of the present invention, the amount of lubricant used is 0.5% to 15% of the drug mass, such as 0.5%, 1.0%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, 10%, 10.5%, 11%, 11.5%, 12%, 12.5%, 13%, 13.5%, 14%, 14.5%, and 15%.
[0014] In some embodiments of the present invention, the particle size of the micronized drug is 0.5–5 μm.
[0015] The median particle size of the lubricant is 1.0–50.0 μm, preferably 1.0–10.0 μm.
[0016] In some embodiments of the present invention, the temperature of the temperature- and humidity-controlled airflow is room temperature to 220°C, and the humidity is 0% to 90%.
[0017] Preferably, the airflow temperature is 60–95°C, more preferably 70–85°C, and even more preferably 70–80°C.
[0018] In some embodiments of the present invention, the airflow temperature is 73°C or 79°C.
[0019] Preferably, the humidity is 0%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90%.
[0020] In some embodiments of the present invention, the airflow humidity is 10% or 30%.
[0021] The existing technology for obtaining temperature and humidity controlled airflow can be obtained through spray drying equipment, or it may be obtained through other temperature and humidity controlled equipment in the existing technology.
[0022] In some embodiments of the present invention, the time for which the micronized drug and the lubricant are co-suspended in a temperature- and humidity-controlled airflow is 0.5-24 hours, for example, 0.5 hours, 1.0 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 5.5 hours, 6 hours, 6.5 hours, 7 hours, 7.5 hours, 8 hours, 8.5 hours, 9 hours, 9.5 hours, 10 hours, and 10.5 hours. , 11h, 11.5h, 12h, 12.5h, 13h, 13.5h, 14h, 14.5h, 15h, 15.5h, 16h, 16.5h, 17h, 17 .5h, 18h, 18.5h, 19h, 19.5h, 20h, 20.5h, 21h, 21.5h, 22h, 22.5h, 23h, 23.5h, 24h.
[0023] In some embodiments of the present invention, the micronized drug and the lubricant powder are placed in a container, and then a temperature- and humidity-controlled airflow is introduced into the container so that the micronized drug and the lubricant powder are suspended together in the temperature- and humidity-controlled airflow.
[0024] Preferably, the inner wall of the container has a coating to prevent powder adhesion, and preferably, the coating is a PTFE coating.
[0025] In some embodiments of the present invention, before the micronized drug and lubricant powder are placed in the container, the inner wall of the container is separately wiped with lubricant.
[0026] Compared with the prior art, the present invention has the following beneficial effects:
[0027] This invention is scientifically designed and ingeniously conceived. It creatively suspends drug micropowder and lubricant in a temperature- and humidity-controlled cyclone to complete their crystallization process. Because the particles continuously rotate in the cyclone, they cannot aggregate with adjacent drug micropowder, thus avoiding particle size increase caused by crystallization after airflow pulverization. This method also reduces drug adhesion to the walls and improves yield. Attached Figure Description
[0028] Appendix Figure 1 This is a schematic diagram of the cyclone processing of the present invention.
[0029] Appendix Figure 2 This is a microscopic morphology image of the drug in Example 1.
[0030] Appendix Figure 3 The image shows the sample wall adhesion before and after cyclone treatment in Example 3.
[0031] Appendix Figure 4 The image shows the XRD pattern of the sample before pulverization in Example 1.
[0032] Appendix Figure 5 The image shows the XRD pattern of the pulverized sample from Example 1.
[0033] Appendix Figure 6 The image shows the XRD pattern of the sample after cyclone suspension treatment in Example 1. Detailed Implementation
[0034] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased commercially.
[0035] The air jet mill used in this embodiment of the invention is an MC. Type 30; a Buchi B-290 small laboratory spray dryer is used to provide the suspended airflow for crystal growth. The temperature and humidity of the suspended airflow are controlled by controlling the inlet temperature and the water injection rate. Particle size is determined using a New Partek laser particle size analyzer, model HELOS.
[0036] Example 1
[0037] This embodiment discloses the method of the present invention for stabilizing the particle size of micro-powdered drugs by using cyclone treatment:
[0038] (1) Grinding the drug: Weigh 3.5g of glycopyrronium bromide and use MC... A 30-type air jet mill was used. The venturi pressure was adjusted to 7.0 bar for feeding, the grinding pressure was 6.5 bar, and the grinding time was 10 minutes. The pulverized glycopyrronium bromide sample was then collected.
[0039] (2) Cyclone treatment: The glycopyrronium bromide sample obtained in step (1) was cyclone treated using a Buchi B-290 laboratory small spray dryer. Specifically, the inner wall of the collection bottle, which had a PTFE coating, was wiped with magnesium stearate. After wiping with magnesium stearate, the glycopyrronium bromide sample obtained in step (1) was placed in the collection bottle, and then an additional 0.5% (w / w) of magnesium stearate with a median particle size of 5.0 μm was added. Spray drying was turned on, causing the mixture of glycopyrronium bromide particles and magnesium stearate to suspend and rotate in the collection bottle with the drying airflow (e.g., ...). Figure 1 As shown in the figure, the temperature and humidity were kept stable for 6 hours. The inlet temperature of the spray dryer was 160℃, compressed air was used as the atomizing gas, the atomizing gas flow rate was set to 667 L / h, purified water was used for injection at a rate of 1.5 mL / min, and the drying gas flow rate was 38 m³ / min. 3 The outlet temperature was measured at 109℃ per hour. The temperature inside the collection bottle was measured at 73℃ and the humidity at 10% using a thermometer and hygrometer. After the cyclone suspension treatment was completed, the material in the collection bottle was collected, yielding a mixture of treated glycopyrronium bromide particles and magnesium stearate.
[0040] In this embodiment, the mouth of the collection bottle is covered with a film, so that the drug powder and lubricant powder can rotate with the airflow inside the collection bottle, but will not be carried out of the collection bottle by the airflow.
[0041] The particle size of glycopyrronium bromide before pulverization, glycopyrronium bromide after pulverization, and glycopyrronium bromide / magnesium stearate after cyclone treatment in step (2) in this embodiment was detected by laser particle size analyzer. The results are shown in Table 1.
[0042] The pulverized glycopyrronium bromide and the glycopyrronium bromide / magnesium stearate treated by step (2) were stored at 25°C and 40% humidity for 1 week, and their particle size was measured. The results are shown in Table 2.
[0043] Table 1. Results of drug particle size detection in Example 1
[0044]
[0045] Table 2 Results of the drug particle size stability study in Example 1
[0046]
[0047] As shown in Table 1, the particle size of the drug after cyclone treatment is basically the same as that before cyclone treatment, with no significant difference.
[0048] As shown in Table 2, after one week of storage, the particle size of the micronized drug after cyclone treatment was basically the same as that on day 0; while the particle size of the micronized drug without cyclone treatment increased significantly after one week of storage, indicating that the method of the present invention can effectively stabilize the drug particle size.
[0049] The microscopic morphology of the drug in this embodiment is shown in the attached figure. Figure 2 As shown, the upper left image shows the microstructure of glycopyrronium bromide before pulverization; the upper right image shows the microstructure of glycopyrronium bromide / magnesium stearate after cyclone treatment; the lower left image shows the microstructure of glycopyrronium bromide / magnesium stearate after one week of storage following cyclone treatment; and the lower right image shows the microstructure of glycopyrronium bromide powder without cyclone treatment after one week of storage. Figure 1 It can be seen that glycopyrronium bromide has a large particle size before pulverization, and its morphology shows obvious large granular blocks. After air jet milling, the particle size of glycopyrronium bromide decreases. Furthermore, after cyclone treatment, the micronized glycopyrronium bromide did not show significant particle size increase after being stored at 25℃ and 40% relative humidity for one week. In contrast, the micronized glycopyrronium bromide without cyclone treatment showed obvious particle aggregation after being stored at 25℃ and 40% relative humidity for one week.
[0050] Example 2
[0051] This embodiment discloses the method of the present invention for stabilizing the particle size of micro-powdered drugs by using cyclone treatment:
[0052] (1) Grinding the drug: Weigh 2.1g of glycopyrronium bromide and use MC... A 30-type air jet mill was used. The venturi pressure was adjusted to 7.0 bar for feeding, the grinding pressure was 5.5 bar, and the grinding time was 10 minutes. The pulverized glycopyrronium bromide sample was then collected.
[0053] (2) Cyclone treatment: The glycopyrronium bromide sample obtained in step (1) was treated using a Buchi B-290 laboratory small spray dryer. Specifically, the inner wall of the collection bottle, which had a PTFE coating, was wiped with magnesium stearate. After wiping with magnesium stearate, the glycopyrronium bromide sample obtained in step (1) was placed in the collection bottle, and then an additional 1.5% (w / w) of magnesium stearate with a median particle size of 2.15 μm was added. Spray drying was turned on, causing the mixture of glycopyrronium bromide particles and magnesium stearate to rotate in the collection bottle with the drying airflow (e.g., ...). Figure 1 (As shown), maintain stable temperature and humidity for 2 hours. The inlet temperature of the spray dryer was 180℃, compressed air was used as the atomizing gas, the atomizing gas flow rate was set to 667 L / h, purified water was used for injection at a rate of 25 mL / min, and the drying gas flow rate was 38 m³ / min. 3 The outlet temperature was measured at 115℃ per hour. The temperature and humidity inside the collection bottle were measured at 79℃ and 30% using a thermometer and hygrometer, respectively. After cyclone suspension treatment, the material in the collection bottle was collected, yielding a mixture of treated glycopyrronium bromide particles and magnesium stearate.
[0054] The particle size of glycopyrronium bromide before pulverization, glycopyrronium bromide after pulverization, magnesium stearate, and glycopyrronium bromide / magnesium stearate after pulverization and treatment in step (2) were measured using a laser particle size analyzer. The results are shown in Table 3.
[0055] The pulverized glycopyrronium bromide and the glycopyrronium bromide / magnesium stearate treated in step (2) were stored at 25°C and 40% humidity for one week, and their particle size was measured. The results are shown in Table 4.
[0056] Table 3. Results of drug particle size detection in Example 2
[0057]
[0058] Table 4 Results of the drug particle size stability study in Example 2
[0059]
[0060]
[0061] As shown in Table 3, the particle size of the drug after cyclone treatment is basically the same as that before cyclone treatment, with no significant difference.
[0062] As shown in Table 4, after one week of storage, the particle size of the micronized drug after cyclone treatment was basically the same as that on day 0; while the particle size of the micronized drug without cyclone treatment increased significantly after one week of storage, indicating that the method of the present invention can effectively stabilize the drug particle size.
[0063] Example 3
[0064] This embodiment discloses the method of the present invention for stabilizing the particle size of micro-powdered drugs by using cyclone treatment:
[0065] (1) Grinding the drug: Weigh 3.5g of levosalbutamol and use MC... A 30-type air jet mill was used. The venturi pressure was adjusted to 7.0 bar for feeding, the grinding pressure was 6.5 bar, and the grinding time was 10 minutes. The ground L-salbutamol sample was then collected.
[0066] (2) Cyclone treatment: The L-salbutamol sample obtained in step (1) was treated using a Buchi B-290 laboratory small spray dryer, specifically:
[0067] The inner wall of the collection bottle was wiped with phospholipid porous microspheres. Then, the L-salbutamol sample obtained in step (1) was placed in the collection bottle, and phospholipid porous microspheres at 5% of the L-salbutamol mass were added. Spray drying was then started, allowing the sample powder to rotate with the drying airflow within the collection bottle. Temperature and humidity were kept stable for 8 hours. The inlet temperature of the spray dryer was 160℃, compressed air was used as the atomizing gas, and the atomizing gas flow rate was set to 667 L / h. Purified water was used for injection at a rate of 1.5 mL / min, and the drying gas flow rate was 38 m³ / min. 3 The outlet temperature was measured at 109℃ / h. The temperature inside the collection bottle was measured at 73℃ and the humidity at 10% using a thermometer and hygrometer. After cyclone suspension treatment, the material in the collection bottle was collected, yielding a mixture of treated L-salbutamol and phospholipid porous microspheres.
[0068] The preparation method of phospholipid porous microspheres in this embodiment is as follows: DSPC (1,2-distearate-sn-glycerol-3-phosphocholine) and anhydrous calcium chloride are weighed and added to purified water at a temperature above 55°C. Perfluorooctane (PFOB) is added as the oil phase. An emulsion raw material is prepared by high-speed shearing and high-pressure homogenization. Then, phospholipid porous microspheres with a median particle size of 2.3 μm (composed of 93.4 wt.% DSPC and 6.6 wt.% anhydrous calcium chloride) are obtained under spray drying conditions.
[0069] The particle size of L-salbutamol before pulverization, L-salbutamol after pulverization, phospholipid porous microspheres, and L-salbutamol / phospholipid porous microspheres after pulverization and treatment in step (2) were measured using a laser particle size analyzer. The results are shown in Table 5.
[0070] The L-salbutamol / phospholipid porous microspheres treated in step (2) were stored at 25°C and 40% humidity for one week, and their particle size was measured. Separately, L-salbutamol and 5% by weight of its phospholipid porous microspheres were mixed evenly and stored at 25°C and 40% humidity for one week, and their particle size was measured. The results are shown in Table 6.
[0071] Table 5. Results of drug particle size detection in Example 3
[0072]
[0073] Table 6 Results of the drug particle size stability study in Example 3
[0074]
[0075] Example 4
[0076] This embodiment uses sample yield as an indicator to investigate different ratios of drug to lubricant.
[0077] This embodiment uses the method of Example 1, the difference being the ratio and type of glycopyrronium bromide to lubricant. The specific ratios and corresponding recovery rates are shown in Table 7.
[0078] Table 7 Recovery rates after treatment with different lubricant groups
[0079] Glycerone bromide dosage Lubricant ratio Recovery rate of treated samples Recovery rate 500.1mg 0 38.0mg 7.6％ 295.4mg 5% magnesium stearate 99.6mg 33.7％ 274.3mg 5% Phospholipid Porous Microspheres 262.1mg 95.6％
[0080] Note: Recovery rate is expressed as the ratio of powder that can be poured out of the container after cyclone treatment to the amount of sample added. Powder adhering to the container wall cannot actually form a swirling suspension, therefore it is not included in the calculation of recovered powder mass.
[0081] The phospholipid porous microspheres used in this embodiment were prepared according to the method in Example 3.
[0082] The sample wall adhesion status before and after cyclone treatment in each group of this embodiment is shown in the attached figure. Figure 3 As shown.
[0083] From Table 7 and Figure 3 It is known that micronized glycopyrronium bromide, due to its small particle size and very large specific surface area, easily adheres to the container wall during cyclone treatment, making it impossible to form a suspension in the cyclone. The treated glycopyrronium bromide powder could only be scraped off the container wall with a spatula, resulting in an extremely low yield of only 7.6%. Adding 5% magnesium stearate to the glycopyrronium bromide powder reduced the adhesion of the sample to the container wall, and the recovery rate after cyclone treatment reached 33.7%.
[0084] Microspheres prepared using phospholipid emulsification are commonly used as carriers for inhaled formulations (aerosols or powders), but due to their high hygroscopicity, they have not been used as lubricants. The applicant unexpectedly discovered that, in this invention, adding 5% phospholipid microspheres to glycopyrronium bromide micropowder significantly reduces adhesion to the container walls during cyclone treatment, allowing the powder to maintain a good rotating suspension within the container for an extended period. After cyclone treatment, the powder can simply be poured out, achieving a recovery rate of 95.6%.
[0085] Example 5
[0086] Changes in crystal form of glycopyrronium bromide before and after micronization and before and after suspension crystallization. Glycerronium bromide was micronized using the method described in Example 1, and then suspended in a cyclone separator using a temperature- and humidity-controlled airflow to grow crystals. XRD analysis was performed on the glycopyrronium bromide before and after micronization and after crystallization to identify changes in crystal form. Results are as follows: Figure 4As shown, glycopyrronium bromide exhibits a very distinct crystalline structure before pulverization, with high diffraction peak intensities, reaching over 7500. However, after micronization, the diffraction peak intensities decrease significantly, with the strongest peak intensity only around 500. Furthermore, within the 2θ angle range of 15-30°, the diffraction pattern shows a distinct upward bulge, indicating the presence of amorphous components in the micronized glycopyrronium bromide. After suspension crystallization in a cyclone separator, the amorphous components of glycopyrronium bromide transform into crystals, with the strongest diffraction peak intensity reaching over 1250, and the bulge within the 2θ angle range weakening, indicating a reduction in amorphous components and their transformation into crystalline form.
[0087] The above embodiments are merely one of the preferred embodiments of the present invention and should not be used to limit the scope of protection of the present invention. Any modifications or refinements made to the main design concept and spirit of the present invention that are not of substantial significance, but solve the same technical problem as the present invention, should be included within the scope of protection of the present invention.
Claims
1. A method for stabilizing the particle size of micronized drugs, characterized in that, include: Micronized drug powder and lubricant powder are placed in a container. The top opening of the container is connected to the bottom of a cyclone separator, and the opening is covered with a membrane. Temperature and humidity controlled cyclone airflow is introduced into the container through the cyclone separator, so that the drug micronized powder and lubricant are suspended together in the temperature and humidity controlled cyclone for 0.5-24 hours and will not be carried out of the container by the airflow. The drug micronized powder undergoes amorphous crystal transformation in the suspended airflow, thereby stabilizing the drug particle size. The drug has a particle size of 0.5~5 µm, and the lubricant has a median particle size of 1.0~50.0 µm; the amount of lubricant used is 0.5~15% of the drug mass. The inner wall of the container has a coating to prevent powder from adhering.
2. The method for stabilizing the particle size of micro-powdered drugs according to claim 1, characterized in that, The drug includes drugs delivered to the lungs via oral inhalation.
3. The method for stabilizing the particle size of micronized drugs according to claim 1, characterized in that, The drugs include short-acting muscarinic receptor antagonists, long-acting muscarinic receptor antagonists, short-acting β2 receptor agonists, and long-acting β2 receptor agonists.
4. The method for stabilizing the particle size of micronized drugs according to claim 1, characterized in that, The drug is salbutamol sulfate, levosalbutamol, glycopyrronium bromide, or tiotropium bromide.
5. A method for stabilizing the particle size of micronized drugs according to any one of claims 1-3, characterized in that, The lubricant includes at least one of phospholipid porous microspheres, magnesium stearate, L-leucine, trileucine, and lactose.
6. A method for stabilizing the particle size of micronized drugs according to any one of claims 1-3, characterized in that, The median particle size of the lubricant is 1.0~10.0 μm.
7. A method for stabilizing the particle size of micronized drugs according to any one of claims 1-3, characterized in that, The temperature and humidity of the cyclone airflow are room temperature to 220℃ and humidity to 0 to 90%.
8. A method for stabilizing the particle size of micronized drugs according to any one of claims 1-3, characterized in that, The coating is a PTFE coating.
9. The method for stabilizing the particle size of micro-powdered drugs according to claim 8, characterized in that, Before placing the micronized drug and lubricant powder into the container, the inner wall of the container should be wiped with lubricant separately.