A new crystalline form of piroxicam and its preparation method and application
A new crystal form of piroxicam, VIII, was prepared by heating and melting piroxicam with polyethylene glycol and then rapidly cooling and crystallizing. This method solved the problems of low elasticity and insufficient tableting performance of piroxicam crystals, achieving better mechanical properties and stability, and making it suitable for anti-inflammatory drugs.
Patent Information
- Application Number
- CN202410324354.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-03-21
- Publication Date
- 2025-11-18
- Estimated Expiration
- 2044-03-21
AI Technical Summary
Existing piroxicam crystals have low elasticity and limited tableting performance, making it difficult to meet the needs of tablet processing.
A new crystalline form of piroxicam, VIII, was prepared by mixing piroxicam with polyethylene glycol, heating and melting the mixture, then rapidly cooling and holding it at that temperature to allow for crystallization. The formation of the pure phase crystalline form was ensured by controlling the specific temperature and time.
The prepared piroxicam new crystal form VIII has mechanical elasticity, can bend and rebound under mechanical pressure, has better tableting performance and stability, and is suitable for anti-inflammatory drugs.
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Figure CN118324756B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to a new crystal form of piroxicam, its preparation method, and its application, belonging to the field of pharmaceutical chemistry technology. Background Technology
[0002] Piroxicam, also known as piroxicam, is a nonsteroidal anti-inflammatory drug (NSAID) that primarily has analgesic and anti-inflammatory effects. Its mechanism of action involves reducing the synthesis and release of prostaglandins in the body. Clinically, piroxicam is mainly used to treat joint pain, and sometimes it can also treat toothache, sprains, and lumbar muscle strain. Its structural diagram is shown below:
[0003]
[0004] Piroxicam was first synthesized by Lombardino et al. in 1972 and launched in the UK in March 1985. It is now available in various formulations, including tablets, capsules, injections, liniments, and gels. In June 1982, Pfizer launched it under the brand name Feldene, and Toyama Chemical Industry launched it under the brand name Baxo. In 1998, the UK market introduced the topical formulation piroxicam gel, which was included in the British Pharmacopoeia in the same year. In 2000, Japan first launched a 0.5% piroxicam gel, liniment, or ointment. In 1996, South Korea's Sunkyong Industrial Co., Ltd. first launched a matrix-type patch.
[0005] Currently, seven polymorphs of piroxicam have been reported in the literature. In 1982, Kojic-Prodic et al. reported polymorph I (Acta Crystallogr., Sect. B: Struct. Crystallogr. Cryst. Chem. 1982, 38, 2948-2951); in 1988, Reck et al. reported polymorph α1 (Pharmazie. 1988, 43, 477-481); in 2004, Sheth et al. reported polymorph II (Cryst. Growth Des., 2004, 4, 1091-1098); and in 1991… F. et al. reported crystal form III (Int. J. Pharm. 1991, 68, 35-41); Thomas, LH et al. reported crystal form IV in 2016 (Chem. Commun. 2016, 52, 7372-7375); 2015 Z. et al. reported crystal form V (J. Pharm. Sci. 2015, 104, 1909-1918); Yao et al. reported crystal forms VI and VII in 2020 (Cryst. Growth Des. 2020, 20, 7874-7881).
[0006] Besides its pharmaceutical uses, piroxicam is also an organic crystal. Research on the mechanical properties of organic crystals is quite popular, and there are currently few reports on single-component organic crystals with mechanical properties. Developing a new crystal form of piroxicam to improve its elasticity and tableting properties will lead to better applications in piroxicam tablet processing. Summary of the Invention
[0007] This invention addresses the shortcomings of existing technologies by providing a new crystalline form of piroxicam, its preparation method, and its applications, thus solving the problems of low elasticity and limited tableting performance of existing piroxicam crystals.
[0008] The technical solution of the present invention to solve the above-mentioned technical problems is as follows: a new crystalline form of piroxicam, wherein the X-ray diffraction pattern of the new crystalline form of piroxicam has characteristic diffraction peaks at the following 2θ angles: 7.00°, 7.30°, 8.78°, 9.80°, 12.34°, 13.63°, 14.25°, 15.26°, 15.70°, 15.84°, 16.84°, 17.31°, 17.64°, 18.32°, 19.01°, 20.51°, 20.78°, 21.76°, 22.61°, 23.80°, 24.55°, 25.40°, 28.18°, with an error of ±0.1°.
[0009] This invention also discloses a method for preparing a new crystalline form of pyroxicam, wherein the preparation method is as follows:
[0010] S1, Preparation of Seed Crystals
[0011] Piroxicam and polyethylene glycol are ground and mixed to obtain a mixture. The mixture is heated and melted, and then rapidly cooled to 58-62℃ and kept at that temperature to crystallize. Finally, the seed crystals of the new crystalline form VIII of piroxicam can be obtained on the surface of the melt.
[0012] Preparation of S2 and the new crystalline form VIII of piroxicam
[0013] After heating and melting piroxicam, the temperature is rapidly reduced to 125-135°C. Seeds of the new piroxicam crystal form VIII are added, and crystal growth is carried out under the condition of holding at 125-135°C. After the crystal growth is completed, the temperature is cooled to room temperature to obtain the new piroxicam crystal form VIII.
[0014] Furthermore, the mass fraction of polyethylene glycol in the mixture of step S1 is 8-12%.
[0015] Furthermore, the heating and melting temperature in step S1 is 205-215℃.
[0016] Furthermore, the heating and melting temperature in step S2 is 205-215℃.
[0017] Furthermore, in step S1, after the mixture is heated and melted, the time to cool it to 58-62℃ is within 4 seconds, and the time to crystallize at 58-62℃ is 0.5-4 hours.
[0018] Preferably, in step S1, after the mixture is heated and melted, it is rapidly cooled to 60°C and crystallized under a holding temperature condition.
[0019] Furthermore, in step S2, the time taken to rapidly cool piroxicam to 125-135°C after heating and melting it is within 4 seconds.
[0020] Preferably, in step S2, after the piroxicam is heated and melted, it is rapidly cooled to 130°C, and seed crystals of the new piroxicam crystal form VIII are added. Crystal growth is then carried out under a holding temperature of 130°C.
[0021] The present invention also discloses the application of a new piroxicam crystal form in anti-inflammatory drugs.
[0022] The beneficial effects of this invention are:
[0023] (1) The method for preparing the new crystalline form of piroxicam described in this invention is simple, and a pure phase crystalline form can be obtained by adding a specific type of polymer.
[0024] (2) The crystal of the new piroxicam crystal form described in this invention can bend under mechanical pressure, and can spring back to its original shape after the mechanical pressure is removed, thus having mechanical elasticity.
[0025] (3) Compared with the raw material crystal form, the new crystal form of piroxicam described in this invention has better tableting performance.
[0026] (4) The new crystalline form of piroxicam described in this invention has good stability. Attached Figure Description
[0027] Figure 1 The powder X-ray diffraction pattern is for crystal form VIII.
[0028] Figure 2 This is the unit cell diagram of crystal form VIII.
[0029] Figure 3 This is the DSC spectrum of crystal form VIII.
[0030] Figure 4 The Raman spectrum is for crystal form VIII.
[0031] Figure 5 This is a diagram showing the surface crystallization process of the piroxicam and polyethylene glycol mixture melt at 60°C in Example 1.
[0032] Figure 6 This is a diagram showing the surface crystallization of the piroxicam and polyethylene glycol mixture melt at 60℃ for 6 hours in Comparative Example 1.
[0033] Figure 7 The diagram shows the elastic bending process of the piroxicam crystal VIII prepared in Example 1.
[0034] Figure 8 This is a comparison chart of the tableting performance of crystal form VIII and the raw material crystal form.
[0035] Figure 9 The Raman spectrum is for crystal form III;
[0036] Figure 10 The XRD pattern is for crystal form III. Detailed Implementation
[0037] The specific embodiments of the present invention will be described in detail below. The present invention can be implemented in many other ways different from those described herein, and those skilled in the art can make similar modifications without departing from the spirit of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed.
[0038] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used is for describing particular embodiments only and is not intended to limit the invention.
[0039] A new crystalline form of piroxicam, such as Figure 1 As shown, the X-ray diffraction pattern of the new pyroxicam crystal form has characteristic diffraction peaks at the following 2θ angles: 7.00°, 7.30°, 8.78°, 9.80°, 12.34°, 13.63°, 14.25°, 15.26°, 15.70°, 15.84°, 16.84°, 17.31°, 17.64°, 18.32°, 19.01°, 20.51°, 20.78°, 21.76°, 22.61°, 23.80°, 24.55°, 25.40°, and 28.18°, with an error of ±0.1°.
[0040] A method for preparing a new crystalline form of piroxicam according to claim 1, wherein the preparation method comprises:
[0041] S1, Preparation of Seed Crystals
[0042] Piroxicam and polyethylene glycol are ground and mixed to obtain a mixture. The mixture is heated and melted, and then rapidly cooled to 58-62℃ and kept at that temperature to crystallize. Finally, the seed crystals of the new crystalline form VIII of piroxicam can be obtained on the surface of the melt.
[0043] Preparation of S2 and the new crystalline form VIII of piroxicam
[0044] Piroxicam was heated and melted, then rapidly cooled to 125-135°C. Seed crystals of the new piroxicam crystalline form VIII were added, and crystal growth was carried out under a holding temperature of 125-135°C. After crystal growth, the crystals were cooled to room temperature to obtain the new piroxicam crystalline form VIII. The unit cell diagram of crystalline form VIII is shown below. Figure 2 As shown.
[0045] Specifically, the mass fraction of polyethylene glycol in the mixture of step S1 is 8-12%.
[0046] Specifically, the average molecular weight of the polyethylene glycol ranges from 800 to 800,000.
[0047] Preferably, the mass fraction of polyethylene glycol in the mixture of step S1 is 10%.
[0048] Specifically, the heating and melting temperature in step S1 is 205-215℃.
[0049] Specifically, the heating and melting temperature in step S2 is 205-215℃.
[0050] Specifically, in step S1, after the mixture is heated and melted, the time to cool it to 58-62℃ is within 4 seconds, and the time to keep it at 58-62℃ for crystallization is 0.5-4 hours.
[0051] Specifically, in step S1, after the mixture is heated and melted, it is rapidly cooled to 60°C and crystallized under the holding temperature condition.
[0052] Specifically, in step S2, the time taken to rapidly cool piroxicam to 125-135°C after heating and melting it is within 4 seconds.
[0053] Specifically, in step S2, after heating and melting piroxicam, the temperature is rapidly reduced to 130°C, and seed crystals of the new piroxicam crystal form VIII are added. Crystal growth is then carried out under the condition of maintaining the temperature at 130°C.
[0054] More specifically, in step S2, after the piroxicam is heated and melted, it is rapidly cooled to 125-135°C. A needle is used to scrape off the VIII crystal seed from the surface of the melt from step S1, and the needle with the seed is then inserted into the melt at 125-135°C to inoculate the crystal. To accelerate crystal growth, multiple seed crystals can be inoculated in the melt. In practice, the crystal growth time can be reasonably controlled based on the amount of raw material in the system and the number of seed crystals inoculated.
[0055] More specifically, the piroxicam raw material used in the embodiments of the present invention is piroxicam crystal form I.
[0056] This invention employs an advanced 3D ED (MicroED) method to determine the single-crystal structure of a novel pyroximate crystal form. A transmission electron microscope (TEM, JEOL jeem-2100LaB6) equipped with a fast Timepix hybrid pixel detector (512x512 pixels, Amsterdam Scientific Instruments) was used. The crystal was continuously rotated using Instamatic software in a 200kV selected-area electron diffraction mode to collect diffraction data. The crystal unit cell and space group were determined using Rotation ED processing software (REDp). The diffraction data were processed using crystallography software (XDS), and the five datasets were merged based on their interrelationships to improve completeness and I / σ(I), ultimately obtaining a single dataset suitable for structure solving and refinement. The merged data was then used for structure solving and refinement using SHELXTL. Within this software package, XPREEP was used to reconfirm the crystal space group and prepare .ins files. The crystal structure was then analyzed using SHELXT software. The obtained crystal structure was refined using ShelXle to obtain the final crystal structure, which is a triclinic crystal system with space group P1, a = 7.53(9), b = 13.09(2), c = 20.84(12), alpha = 75.45(58), beta = 84.64(49), gamma = 84.28(90), and the cell volume is... Cell stacking as Figure 2 As shown, each unit cell contains five piroxicam conformation molecules, with weak molecular interactions primarily consisting of NHO hydrogen bonds. The crystallographic parameters of piroxicam crystal form VIII are shown in Table 1 below.
[0057] Table 1. Crystallographic parameters of pyroxicam crystal form VIII
[0058]
[0059]
[0060] The thermal analysis spectrum of the pyroxicam crystal form VIII is as follows: Figure 3 As shown, it exhibits a distinct melting endothermic peak at 150℃. The Raman spectrum of crystal form VIII is shown below. Figure 4 As shown.
[0061] Example 1
[0062] S1, Preparation of Seed Crystals
[0063] Piroxicam and polyethylene glycol were ground and mixed to obtain a mixture, wherein the mass fraction of polyethylene glycol in the mixture was 10%. 2-3 mg of the mixture was placed on a glass slide and heated to 210°C to melt. The temperature was then lowered to 60°C within 4 seconds and maintained at 60°C for 4 hours to crystallize. The mixture was then placed at room temperature, and seed crystals of the new piroxicam crystal form VIII were finally obtained on the surface of the melt. The crystallization process at different time points under a microscope during crystallization at 60°C is shown below. Figure 5 As shown.
[0064] Preparation of S2 and the new crystalline form VIII of piroxicam
[0065] 20 mg of piroxicam was melted at 210°C and then rapidly cooled to 130°C within 4 seconds. Crystallization VIII seed crystals from the surface of the melt in step S1 were scraped off using a needle. The needle containing the seed crystals was then inserted into the 130°C melt to achieve seeding. The melt was held at 130°C for 0.5 hours for crystal growth. After crystal growth, the melt was cooled to room temperature to obtain the new piroxicam crystallization VIII. The XRD pattern of the obtained product was obtained after grinding and pulverizing. Figure 1 As shown.
[0066] Example 2
[0067] S1, Preparation of Seed Crystals
[0068] Piroxicam and polyethylene glycol were ground and mixed to obtain a mixture, wherein the mass fraction of polyethylene glycol in the mixture was 8%. 2-3 mg of the mixture was placed on a glass slide, heated to 210°C to melt, and then cooled to 58°C within 4 seconds. The mixture was kept at 58°C for 4 hours to crystallize, and then placed at room temperature. Finally, the seed crystals of the new crystal form VIII of piroxicam could be obtained on the surface of the melt.
[0069] Preparation of S2 and the new crystalline form VIII of piroxicam
[0070] 30 mg of piroxicam was melted at 210°C and then rapidly cooled to 135°C within 4 seconds. Crystallization VIII seed crystals from the surface of the melt in step S1 were scraped off using a needle. The needle containing the seed crystals was then inserted into the 135°C melt to achieve seeding. The melt was held at 135°C for 1 hour to allow crystal growth. After crystal growth, the melt was cooled to room temperature to obtain the new piroxicam crystallization VIII. The XRD pattern of the obtained product was obtained after grinding and pulverizing. Figure 1 As shown.
[0071] Example 3
[0072] S1, Preparation of Seed Crystals
[0073] Piroxicam and polyethylene glycol were ground and mixed to obtain a mixture, wherein the mass fraction of polyethylene glycol in the mixture was 12%. 2-3 mg of the mixture was placed on a glass slide, heated to 210°C to melt, and then cooled to 62°C within 4 seconds. The mixture was kept at 62°C for 4 hours to crystallize, and then placed at room temperature. Finally, the seed crystals of the new crystal form VIII of piroxicam could be obtained on the surface of the melt.
[0074] Preparation of S2 and the new crystalline form VIII of piroxicam
[0075] 30 mg of piroxicam was melted at 210°C and then rapidly cooled to 125°C within 4 seconds. Crystallization VIII seed crystals from the surface of the melt in step S1 were scraped off using a needle. The needle containing the seed crystals was then inserted into the 125°C melt to achieve seeding. The melt was held at 125°C for 1 hour to allow crystal growth. After crystal growth, the melt was cooled to room temperature to obtain the new piroxicam crystallization VIII. The XRD pattern of the obtained product was obtained after grinding and pulverizing. Figure 1 As shown.
[0076] Example 4
[0077] S1, Preparation of Seed Crystals
[0078] Piroxicam and polyethylene glycol were ground and mixed to obtain a mixture, wherein the mass fraction of polyethylene glycol in the mixture was 10%. 2-3 mg of the mixture was placed on a glass slide, heated to 210°C to melt, and then cooled to 60°C within 4 seconds. The mixture was kept at 60°C for 4 hours to crystallize, and then placed at room temperature. Finally, the seed crystals of the new crystal form VIII of piroxicam could be obtained on the surface of the melt.
[0079] Preparation of S2 and the new crystalline form VIII of piroxicam
[0080] 2g of piroxicam was melted at 210°C on an iron plate and then rapidly cooled to 130°C within 4 seconds. Crystal form VIII seeds from the melt surface (from step S1) were scraped off with a needle. The needle containing the seeds was then inserted into the 130°C melt to inoculate the crystals. In this embodiment, the seeds were inoculated three times. Crystal growth was carried out at 130°C for 2 hours. After crystal growth, the mixture was cooled to room temperature to obtain the new piroxicam crystal form VIII. The XRD pattern of the powdered piroxicam was then measured. Figure 1 As shown.
[0081] Comparative Example 1
[0082] Seed crystals were prepared using the same method as in Example 1, except that crystallization was carried out at 60°C for 6 hours. The crystallization pattern on the melt surface under a microscope is as follows. Figure 6 As shown.
[0083] Depend on Figure 5 and Figure 6The comparison shows that if the crystallization time exceeds 4 hours during seed crystal preparation, crystal form III will appear on the melt surface, resulting in mixed crystals. Therefore, the crystallization time conditions specified in this invention are more conducive to obtaining crystal form VIII.
[0084] Comparative Example 2
[0085] Seed crystals were prepared using the same method as in Example 1, except that the cooling rate was slowed down during seed crystal preparation. After heating the mixture to 210°C and melting it, the temperature was lowered to 60°C in 10 seconds.
[0086] XRD analysis showed that the seed crystals prepared in Comparative Example 2 were mainly of crystal form III. This indicates that slowing down the cooling rate during seed crystal preparation increases the probability of spontaneous crystallization of other crystal forms, which is not conducive to the crystallization of crystal form VIII.
[0087] Comparative Example 3
[0088] Seed crystals were prepared using the same method as in Example 1, except that the crystallization temperature was 50°C during seed crystal preparation.
[0089] The seed crystals prepared in Comparative Example 3 are mainly of crystal form III. This shows that the crystallization temperature specified in this invention is more conducive to obtaining crystal form VIII. If other crystallization temperatures are selected, crystal form III will be nucleated on the surface of the melt first, rapidly consuming the melt and preventing crystal form VIII from crystallizing.
[0090] Comparative Example 4
[0091] Seed crystals were prepared using the same method as in Example 1, except that polyethylene glycol was not added.
[0092] The seed crystal prepared in Comparative Example 4 is crystal form III (Raman and XRD patterns of crystal form III are shown in [reference needed]). Figure 9 and Figure 10 ).
[0093] This demonstrates that adding polyethylene glycol during the preparation of crystal form VIII seed crystals is beneficial for accelerating the nucleation rate of crystal form VIII and for the directional induction of crystal form VIII.
[0094] Comparative Example 5
[0095] Seed crystals were prepared using the same method as in Example 1, except that in step S2, the cooling rate was slowed down, and after the mixture was heated to 210°C and melted, it was cooled to 130°C in 10 seconds.
[0096] The piroxicam crystal obtained in Comparative Example 5 was found to be a heteromorphic crystal by XRD analysis. This shows that the cooling time specified in this invention is more conducive to obtaining pure phase crystal form VIII. Exceeding the time specified in this invention will increase the probability of spontaneous crystallization of its crystal form, which is not conducive to obtaining pure phase crystal form VIII.
[0097] Comparative Example 6
[0098] Seed crystals were prepared using the same method as in Example 1, except that in step S2, the crystallization temperature was 100°C (lower than the crystallization temperature specified in this invention).
[0099] The piroxicam crystal obtained in Comparative Example 6 was found to be a heterogeneous crystal by XRD analysis.
[0100] Comparative Example 7
[0101] Seed crystals were prepared using the same method as in Example 1, except that in step S2, the crystallization temperature was 150°C (higher than the crystallization temperature specified in this invention).
[0102] The piroxicam crystal obtained in Comparative Example 7 was found to be a heterogeneous crystal by XRD analysis.
[0103] A comparison of the experimental results of Comparative Examples 6-7 and Example 1 shows that at the crystallization temperature specified in this invention, the crystal growth rate of crystal form VIII is relatively fast, which is beneficial for its rapid production. At other temperatures, the probability of spontaneous crystallization of its crystal form will increase, which is not conducive to obtaining pure-phase crystal form VIII.
[0104] Elasticity and tableting properties were tested on the pyroximate form VIII prepared in the embodiments of the present invention:
[0105] The piroxicam crystal VIII obtained in Example 1, when subjected to a certain mechanical pressure, can bend and spring back to its original shape, i.e., it exhibits elasticity. Figure 7 As shown.
[0106] In addition, the piroxicam crystal form VIII obtained in Example 4 was ground into powder and then compressed into tablets. The same compression process was then performed using raw material crystal form I, as shown in the table below. Figure 8 As shown, by Figure 8 It can be seen that the piroxicam crystal form VIII of the present invention has better tableting performance. (Tableting conditions: 120 mg of sample without any excipients was compressed in a 10 mm diameter mold at a pressure of 25 kg / cm for 30 seconds. These tablets were then equilibrated in sealed glass vials for 24 hours before being photographed.)
[0107] Furthermore, the produced crystal form VIII, after being stored at room temperature and dry for 12 months, can still be used as a seed crystal for mass production, indicating that the sample has good stability.
[0108] In addition, the dissolution rate of the tablets made from piroxicam crystal form VIII and polyacrylic acid resin (with a mass ratio of piroxicam crystal form VIII to polyacrylic acid resin of 1:1) obtained in this invention was measured and was almost the same as that of existing drug tablets.
[0109] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are exhaustively listed. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.
[0110] For those skilled in the art, various modifications and improvements can be made without departing from the concept of the present invention, and these modifications and improvements are all within the scope of protection of the present invention. The scope of protection of the present invention is defined by the appended claims.
Claims
1. A method for preparing a pyroxicam crystal form, characterized in that, The preparation method is as follows: S1, Preparation of Seed Crystals Piroxicam and polyethylene glycol were ground and mixed to obtain a mixture. The mixture was then heated to melt, rapidly cooled to 58-62℃, and crystallized under these conditions. Finally, piroxicam crystals of form VIII were obtained on the surface of the melt. The mass fraction of polyethylene glycol in the mixture was 8-12%. Preparation of S2 and Pyroxicam Crystal Form VIII After heating and melting piroxicam, the temperature is rapidly reduced to 125-135°C. Seeds of piroxicam crystal form VIII are added, and crystal growth is carried out under the condition of holding at 125-135°C. After the crystal growth is completed, the temperature is cooled to room temperature to obtain the piroxicam crystal form VIII. In step S1, after the mixture is heated and melted, the time to cool it to 58-62℃ is within 4 seconds, and the time to crystallize at 58-62℃ is 0.5-4 hours. In step S2, the time taken to rapidly cool piroxicam to 125-135°C after heating and melting it is within 4 seconds. The X-ray diffraction pattern of the piroxicam crystal form VIII has characteristic diffraction peaks at the following 2θ angles: 7.00°, 7.30°, 8.78°, 9.80°, 12.34°, 13.63°, 14.25°, 15.26°, 15.70°, 15.84°, 16.84°, 17.31°, 17.64°, 18.32°, 19.01°, 20.51°, 20.78°, 21.76°, 22.61°, 23.80°, 24.55°, 25.40°, and 28.18°, with an error of ±0.1°.
2. The method for preparing a pyroximate crystal form according to claim 1, characterized in that, The heating and melting temperature in step S1 is 205-215℃.
3. The method for preparing a pyroximate crystal form according to claim 1, characterized in that, The heating and melting temperature in step S2 is 205-215℃.
4. The method for preparing a pyroximate crystal form according to claim 1, characterized in that, In step S1, after the mixture is heated and melted, it is rapidly cooled to 60°C and crystallized under the holding temperature condition.
5. The method for preparing a pyroximate crystal form according to claim 1, characterized in that, In step S2, after heating and melting piroxicam, the temperature is rapidly reduced to 130°C, and seed crystals of piroxicam crystal form VIII are added. Crystal growth is then carried out under the condition of holding at 130°C.
6. An application of the pyroxicam crystal form prepared by the preparation method according to any one of claims 1-5, characterized in that, The piroxicam crystal form is used in the preparation of anti-inflammatory drugs.