Solperidol caprate hydrochloride crystal form as well as preparation method and application thereof
By converting decanoic acid haloperidol to decanoic acid haloperidol hydrochloride, the problems of low melting point and thermosensitive degradation of decanoic acid haloperidol were solved, and stable crystal forms A and B were prepared, realizing the feasibility and processability of oral solid dosage forms.
Patent Information
- Application Number
- CN202510936685.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-07-08
- Publication Date
- 2025-10-31
AI Technical Summary
The low melting point, thermosensitive degradation, and tendency to clump haloperidol decanoate limit the development of other dosage forms, especially oral tablets, which have poor stability and formability.
By converting decanoic acid haloperidol to decanoic acid haloperidol hydrochloride, and through salt form modification and excipient optimization, stable decanoic acid haloperidol hydrochloride crystal forms A and B were prepared, increasing the melting point to approximately 195℃, which is suitable for tableting processes.
It significantly improves the chemical and physical stability of haloperidol decanoate, realizes the feasibility and processability of oral solid dosage forms, solves the problems of low melting point and heat-sensitive degradation, and ensures the stability and formability of tablets.
Smart Images
Figure SMS_1 
Figure SMS_2 
Figure SMS_3
Abstract
Description
Technical Field
[0001] This invention belongs to the field of medicinal chemistry, specifically relating to a crystalline form of decanoic acid haloperidol hydrochloride, its preparation method, and its application. Background Technology
[0002] Modifying the crystal form of active pharmaceutical ingredients using crystal engineering techniques to obtain superior crystal forms that are more suitable for production and have better physicochemical properties is a new "shortcut" in drug development. Drug salt formation is one method of drug crystal form modification, which can change the protonated state of the active pharmaceutical ingredient, further altering the drug's physicochemical properties, such as solubility and stability.
[0003] Haloperidol is a typical antipsychotic drug, primarily used to treat acute and chronic schizophrenia, mania, and Tourette syndrome. Haloperidol preparations have been used clinically for many years, with dosage forms including tablets, capsules, injections, and oral solutions. Different dosage forms of haloperidol have their own characteristics and advantages in clinical application. Doctors will comprehensively consider factors such as the patient's specific condition, age, physical condition, and medication adherence to choose the most suitable dosage form for treatment.
[0004] Haloperidol Decanoate is an antipsychotic drug and a long-acting form of haloperidol. The structural formulas of haloperidol and haloperidol Decanoate are shown below:
[0005]
[0006] Haloperidol decanoate injection is indicated for schizophrenia patients requiring long-term parenteral antipsychotic therapy. Haloperidol decanoate injection is marketed in many countries and regions, including Europe, America, and Japan, and has been used safely in clinical practice for over 40 years.
[0007] Currently, haloperidol decanoate is only available in injection form; there are no reports of other dosage forms (such as tablets). The main reason is that haloperidol decanoate has the following drawbacks:
[0008] 1. Low melting point (approximately 42°C): During conventional tableting, it is prone to softening and sticking due to frictional heat or pressure, making it impossible to form complete tablets.
[0009] 2. Thermosensitive degradation: When the processing temperature is close to the melting point, the drug may undergo crystal transformation or decomposition, affecting the uniformity of content.
[0010] 3. Clumping: It tends to clump together, resulting in poor stability of the tablets during storage.
[0011] These defects have limited the development of other dosage forms of haloperidol decanoate (such as oral tablets). Therefore, improvements are needed to overcome the technical problems existing in the current technology.
[0012] Through extensive research, the inventors have made a groundbreaking discovery: converting decanoic acid haloperidol to decanoic acid haloperidol hydrochloride (the structural formula of decanoic acid haloperidol hydrochloride is shown below) significantly increases its melting point to approximately 195°C, and its physicochemical properties are more suitable for tableting processes. Through the synergistic effect of salt form modification and excipient optimization, tablets with high stability can be developed. Simultaneously, two crystalline forms of decanoic acid haloperidol hydrochloride, namely crystalline forms A and B, have been discovered.
[0013] Summary of the Invention
[0014] The purpose of this invention is to provide a crystalline form of decanoic acid haloperidol hydrochloride, its preparation method, and its application. This crystalline form of decanoic acid haloperidol hydrochloride effectively improves the physicochemical properties of decanoic acid haloperidol, exhibiting significant chemical and physical stability, and is suitable for development into oral solid dosage forms.
[0015] To achieve the objectives of this invention, the following implementation scheme is provided.
[0016] In one embodiment, the present invention provides a decanoic acid fluoropiperidine hydrochloride crystal form A, wherein the X-ray powder diffraction pattern of crystal form A has characteristic peaks at 2θ values of 3.73°, 7.41°, 11.11°, 18.56°, 22.31°, 26.09°, and 29.89° ± 0.2°.
[0017] In some embodiments, the X-ray powder diffraction pattern of decanoic acid haloperidol hydrochloride crystal form A is as follows: Figure 1 As shown.
[0018] In another embodiment, the present invention provides a method for preparing decanoic acid haloperidol hydrochloride crystal form A, comprising dissolving decanoic acid haloperidol in solvent 1, stirring, slowly adding hydrochloric acid dropwise to the decanoic acid haloperidol solution, reacting at 10-30°C, filtering after the reaction is complete, and drying.
[0019] In some embodiments, the method for preparing decanoic acid haloperidol hydrochloride crystal form A uses a molar ratio of decanoic acid haloperidol to hydrochloric acid of (1:1.1)-(1:1.5), preferably 1:1.3.
[0020] In some embodiments, the method for preparing decanoic acid haloperidol hydrochloride crystal form A uses a solvent 1 with a volume-to-mass ratio of decanoic acid haloperidol of (10:1)-(25:1) ml / g, preferably 20:1 ml / g.
[0021] In some embodiments, the method for preparing decanoic acid haloperidol hydrochloride crystal form A involves a reaction temperature of room temperature and a stirring time of 1 hour or more, more preferably 3 hours.
[0022] In some embodiments, in the method of the present invention described above, the solvent 1 is selected from at least one of petroleum ether, isopropyl ether, methyl tert-butyl ether, methanol, ethanol, isopropanol, acetone, n-heptane, n-hexane, N,N-dimethylformamide, ethyl acetate, isopropyl acetate, tetrahydrofuran, and acetonitrile, preferably ethyl acetate.
[0023] In another embodiment, the present invention provides a crystalline form B of decanoic acid haloperidol hydrochloride, wherein the X-ray powder diffraction pattern of crystalline form B has characteristic peaks at 2θ values of 3.75°, 7.44°, 10.90°, 15.66°, 16.45°, 16.88°, 18.05°, 19.10°, 19.46°, 19.84°, 20.21°, 22.35°, 24.30°, 25.35°, and 25.84° ± 0.2°.
[0024] In some embodiments, the X-ray powder diffraction pattern of decanoic acid haloperidol hydrochloride crystal form B is as follows: Figure 2 As shown.
[0025] In some embodiments, the present invention also provides a method for preparing decanoic acid haloperidol hydrochloride crystal form B, comprising dissolving decanoic acid haloperidol in solvent 2 at room temperature, stirring, adding hydrochloric acid to the decanoic acid haloperidol solution in one step for reaction, filtering after the reaction is complete, and drying.
[0026] In some embodiments, in the method of the present invention described above, the solvent 2 is selected from at least one of petroleum ether, isopropyl ether, methyl tert-butyl ether, methanol, ethanol, isopropanol, acetone, n-heptane, n-hexane, N,N-dimethylformamide, ethyl acetate, isopropyl acetate, tetrahydrofuran, and acetonitrile, preferably ethyl acetate.
[0027] In some embodiments, the method for preparing decanoic acid haloperidol hydrochloride crystal form B involves a molar ratio of decanoic acid haloperidol to hydrochloric acid of (1:1.1)-(1:1.5), preferably 1:1.3; a volume-to-mass ratio of solvent 2 to decanoic acid haloperidol of (10:1)-(25:1) ml / g, preferably 20:1 ml / g; a reaction temperature of 10-30°C, preferably room temperature; and a stirring time of greater than or equal to 1 hour, more preferably 3 hours.
[0028] In some embodiments, the present invention provides a pharmaceutical composition comprising decanoic acid haloperidol hydrochloride crystal form A or crystal form B, and pharmaceutically acceptable excipients.
[0029] In some embodiments, the present invention provides the use of decanoic acid haloperidol hydrochloride crystal form A or crystal form B in the manufacture of antipsychotic drugs.
[0030] Technical effects:
[0031] The decanoic acid haloperidol hydrochloride crystal forms A and B of the present invention are feasible for oral formulation, such as tablet manufacturing process feasibility. In particular, crystal form A has significant chemical and physical stability compared with decanoic acid haloperidol and decanoic acid haloperidol hydrochloride crystal form B, and has superior drug-likeness and processability for oral formulation. Attached Figure Description
[0032] Figure 1 XRPD pattern of haloperidol hydrochloride crystal form A;
[0033] Figure 2 XRPD pattern of haloperidol hydrochloride crystal form B;
[0034] Figure 3 The XRPD spectrum of the amorphous form of decanoic acid haloperidol hydrochloride is shown. Detailed Implementation
[0035] The following embodiments are provided to describe the present invention in more detail. However, these embodiments are provided only to help further understand the present invention and are not intended to limit the present invention. Those skilled in the art should understand that equivalent substitutions or corresponding improvements made to the content of the present invention still fall within the protection scope of the present invention.
[0036] Unless otherwise specified, all chemical reagents used in the embodiments of this invention are obtained through conventional commercial means or can be prepared by known methods.
[0037] Example 1: Preparation of decanoic acid haloperidol hydrochloride crystal form A
[0038] 55.47 g of decanoic acid haloperidol and 1100 ml of ethyl acetate were added to a 2 L three-necked flask and magnetically stirred until completely dissolved. 11.5 ml of concentrated hydrochloric acid was added to a 25 ml constant pressure funnel. The hydrochloric acid was slowly added dropwise to the three-necked flask at room temperature. After the addition was complete, the reaction was continued with magnetic stirring for 3 hours. The mixture was filtered and dried under reduced pressure at 60 °C to obtain 53.69 g of white powder, which is decanoic acid haloperidol hydrochloride crystal form A. The sample purity (HPLC) was approximately 99.7%, the melting point was 194.7-195.2 °C, and the yield was approximately 90%. The prepared crystal form A was analyzed using X-ray powder diffraction (Cu target). The XRPD pattern of crystal form A is shown below. Figure 1 As shown, the diffraction peaks are shown in Table 1.
[0039] Table 1. List of XRPD diffraction peaks for crystal form A of decanoic acid haloperidol hydrochloride
[0040] serial number 2θ d value Total strength relative strength Half peak width 1 3.73 23.6766 114497 100.0％ 0.143 2 7.41 11.9262 40593 35.5 0.160 3 11.11 7.9599 5528 4.8 0.170 4 12.18 7.2597 686 0.6 0.218 5 16.81 5.2710 2405 2.1 0.205 6 18.56 4.7780 6080 5.3 0.189 7 22.31 3.9822 28032 24.5 0.179 8 23.70 3.7509 1080 0.9 0.289 9 26.09 3.4123 5031 4.4 0.190 10 27.27 3.2682 1180 1.0 0.258 11 29.89 2.9864 3545 3.1 0.179 12 30.95 2.8868 2217 1.9 0.190 13 33.95 2.6387 985 0.9 0.338 14 36.59 2.4539 463 0.4 0.191 15 39.10 2.3021 701 0.6 0.266 16 40.50 2.2258 1040 0.9 0.330 17 41.52 2.1733 383 0.3 0.147 18 42.70 2.1157 2206 1.9 0.281 19 44.34 2.0412 1227 1.1 0.342 20 45.52 1.9913 278 0.2 0.136 21 46.29 1.9596 1575 1.4 0.444
[0041] Example 2: Preparation of decanoic acid haloperidol hydrochloride crystal form B
[0042] 55.47 g of decanoic acid haloperidol and 1100 ml of ethyl acetate were added to a 2 L three-necked flask and magnetically stirred until completely dissolved. 11.5 ml of concentrated hydrochloric acid was added to the flask all at once, and the reaction was continued with magnetic stirring at room temperature for 3 hours. The mixture was filtered and dried under reduced pressure at 60 °C to obtain 53.58 g of white powder, which is decanoic acid haloperidol hydrochloride crystal form B. The sample purity (HPLC) was approximately 99.7%, the melting point was 194.8-195.2 °C, and the yield was approximately 90%. The prepared crystal form B was analyzed using X-ray powder diffraction (Cu target), and the XRPD pattern of crystal form B is shown below. Figure 2 As shown, the diffraction peak list is shown in Table 2.
[0043] Table 2. List of XRPD diffraction peaks for decanoic acid haloperidol hydrochloride crystal form B
[0044] serial number 2θ d value Total strength relative strength Half peak width 1 3.75 23.5378 22817 100.0％ 0.237 2 7.44 11.8680 5646 24.7 0.210 3 8.82 10.0204 209 0.9 0.122 4 10.90 8.1096 3987 17.5 0.238 5 13.70 6.4575 307 1.3 0.192 6 15.66 5.6556 3087 13.5 0.370 7 16.45 5.3838 2013 8.8 0.258 8 16.88 5.2472 1822 8.0 0.180 9 17.56 5.0454 829 3.6 0.934 10 18.05 4.9114 1577 6.9 0.202 11 18.61 4.7643 -151 -0.7 0.050 12 19.10 4.6419 7309 32.0 0.238 13 19.46 4.5582 2192 9.6 0.262 14 19.84 4.4715 2390 10.5 0.287 15 20.21 4.3901 3166 13.9 0.245 16 21.20 4.1872 766 3.4 0.232 17 21.54 4.1217 1903 8.3 0.425 18 21.86 4.0618 549 2.4 0.247 19 22.35 3.9742 3328 14.6 0.203 20 22.95 3.8726 173 0.8 0.083 21 24.30 3.6600 7158 31.4 0.284 22 25.35 3.5101 3653 16.0 0.208 23 25.84 3.4456 3434 15.0 0.316 24 26.53 3.3572 237 1.0 0.071 25 26.95 3.3057 28 0.1 0.100 26 27.57 3.2324 286 1.3 0.135 27 28.41 3.1395 1694 7.4 0.446 28 29.95 2.9806 481 2.1 0.204 29 31.05 2.8781 1942 8.5 0.471 30 31.41 2.8457 986 4.3 0.314 31 32.20 2.7779 1411 6.2 0.331 32 34.16 2.6225 633 2.8 0.379 33 34.75 2.5794 578 2.5 0.274 34 35.64 2.5168 745 3.3 0.278 35 39.19 2.2969 633 2.8 0.391 36 40.70 2.2153 816 3.6 0.427 37 42.84 2.1094 911 4.0 0.301 38 44.45 2.0366 498 2.2 0.288
[0045] Example 3: Stability Tests of Crystal Forms A and B
[0046] Crystal form A and crystal form B were placed in pharmaceutical low-density polyethylene bags, sealed with an outer composite aluminum bag, and subjected to accelerated stability tests to examine the stability of the crystal forms.
[0047] Experimental method: The samples were placed at a temperature of 40±2℃ and a relative humidity of 75±5% for 6 months. Samples were taken once each in the 0th, 1st, 2nd, 3rd and 6th months of the experiment for XRPD detection. The detection results were compared with those in the 0th month. The results are shown in Table 3.
[0048] Table 3. Crystal form detection results of accelerated test samples of crystal form A and crystal form B
[0049]
[0050] The results showed that, through accelerated testing, crystal form A was more stable; crystal form B was unstable and transformed into an amorphous form (its XRPD pattern is shown below). Figure 3 As shown, there are no characteristic peaks.
[0051] Example 4: Solubility investigation of crystal form A, crystal form B and amorphous form
[0052] The solubility of crystal form A, crystal form B and amorphous form was investigated using organic solvents, and the results are shown in Table 4.
[0053] Table 4. Comparison of solubility of decanoic acid haloperidol hydrochloride in crystal form A, crystal form B and amorphous form
[0054]
[0055] Note: "Very soluble" means that 1g of solute dissolves in less than 1ml.
[0056] "Easily soluble" means that 1g of solute dissolves in 1 to less than 10ml.
[0057] Dissolution refers to the dissolution of 1g of solute in 10-30ml.
[0058] Slightly soluble means that 1g of solute dissolves in 30-100ml of water.
[0059] Slightly soluble means that 1g of solute dissolves in 100-1000ml of water.
[0060] Very slight solubility refers to the dissolution of 1g of solute in 1000-less than 10000ml.
[0061] Almost insoluble or insoluble means that 1g of solute cannot be completely dissolved in 10,000ml.
[0062] The results showed that the amorphous powder had better solubility than crystal form A and crystal form B. The solubility of crystal form A and crystal form B was relatively similar.
[0063] Example 5: Preparation of decanoic acid haloperidol tablets
[0064] 1) Prescription (1000 tablets)
[0065]
[0066] 2) Preparation method: The prescribed amounts of decanoic acid haloperidol, microcrystalline cellulose, and corn starch were placed in a three-dimensional mixer and mixed at 10 rpm for 20 minutes. Then, magnesium stearate was added and mixed at 10 rpm for 5 minutes. The mixture was then compressed into tablets with a hardness of 70 N ± 20 N. Result: Due to the softening of the tablets during compression, the hardness was unstable, and there was sticking.
[0067] Example 6: Preparation of decanoic acid haloperidol hydrochloride tablets
[0068] 1) Prescription (1000 tablets)
[0069]
[0070] 2) Preparation method: The prescribed amounts of decanoic acid haloperidol hydrochloride (crystal form A), microcrystalline cellulose, and corn starch were placed in a three-dimensional mixer and mixed at 10 rpm for 20 minutes. Then, magnesium stearate was added and mixed at 10 rpm for 5 minutes. The mixture was then compressed into tablets with a hardness of 70 N ± 20 N. Results: The tableting process was smooth, and the tablet weight and hardness were stable with a smooth surface.
[0071] Example 7: Preparation of decanoic acid haloperidol hydrochloride tablets
[0072] 1) Prescription (1000 tablets)
[0073]
[0074] 2) Preparation method: The prescribed amounts of decanoic acid haloperidol hydrochloride (crystal form B), microcrystalline cellulose, and corn starch were placed in a three-dimensional mixer and mixed at 10 rpm for 20 minutes. Then, magnesium stearate was added and mixed at 10 rpm for 5 minutes. The mixture was then compressed into tablets with a hardness of 70 N ± 20 N. Results: The tableting process was smooth, and the tablet weight and hardness were stable with a smooth surface.
[0075] Example 8: Preparation of decanoic acid haloperidol tablets
[0076] 1) Prescription (1000 tablets)
[0077]
[0078] 2) Preparation method: The prescribed amounts of decanoic acid haloperidol, microcrystalline cellulose, corn starch, anhydrous calcium hydrogen phosphate, and sodium dodecyl sulfate were placed in a three-dimensional mixer and mixed at 10 rpm for 20 minutes. Then, magnesium stearate was added and mixed at 10 rpm for 5 minutes. The mixture was then compressed into tablets with a hardness of 70 N ± 20 N. Result: Due to the softening of the tablets during compression, the hardness was unstable, and there was sticking.
[0079] Example 9: Preparation of decanoic acid haloperidol hydrochloride tablets
[0080] 1) Prescription (1000 tablets)
[0081]
[0082] 2) Preparation method: The prescribed amounts of decanoic acid haloperidol hydrochloride (crystal form A), microcrystalline cellulose, corn starch, anhydrous calcium hydrogen phosphate, and sodium dodecyl sulfate were placed in a three-dimensional mixer and mixed at 10 rpm for 20 minutes. Then, magnesium stearate was added and mixed at 10 rpm for 5 minutes, followed by tableting. Results: The tableting process was smooth, and the tablet weight and hardness were stable, with a smooth and intact tablet surface.
[0083] Example 10: Preparation of decanoic acid haloperidol hydrochloride tablets
[0084] 1) Prescription (1000 tablets)
[0085]
[0086] 2) Preparation method: The prescribed amounts of decanoic acid haloperidol hydrochloride (crystal form B), microcrystalline cellulose, corn starch, anhydrous calcium hydrogen phosphate, and sodium dodecyl sulfate were placed in a three-dimensional mixer and mixed at 10 rpm for 20 minutes. Then, magnesium stearate was added and mixed at 10 rpm for 5 minutes, followed by tableting. Results: The tableting process was smooth, and the tablet weight and hardness were stable, with a smooth and intact tablet surface.
[0087] Example 11 Preparation of Haloperidol Decanoate Tablets
[0088] 1) Prescription (1000 tablets)
[0089]
[0090] 2) Preparation method: The prescribed amounts of decanoic acid haloperidol, microcrystalline cellulose, mannitol, anhydrous calcium hydrogen phosphate, and sodium dodecyl sulfate were placed in a three-dimensional mixer and mixed at 10 rpm for 20 minutes. Granulation was performed using a dry granulator, followed by the addition of magnesium stearate and mixing at 10 rpm for 5 minutes. The mixture was then compressed into tablets with a hardness of 70 N ± 20 N. Results: Due to heating during compression, the granules softened and exhibited severe adhesion. The tablets softened during compression, resulting in unstable hardness and sticking.
[0091] Example 12 Preparation of decanoic acid haloperidol hydrochloride tablets
[0092] 1) Prescription (1000 tablets)
[0093]
[0094] 2) Preparation method: The prescribed amounts of decanoic acid haloperidol hydrochloride (crystal form A), microcrystalline cellulose, mannitol, anhydrous calcium hydrogen phosphate, and sodium dodecyl sulfate were placed in a three-dimensional mixer and mixed at 10 rpm for 20 minutes. Granulation was performed using a dry granulator, followed by the addition of magnesium stearate and mixing at 10 rpm for 5 minutes. Tableting was then performed. Results: The dry granulation and tableting processes were successful, resulting in stable tablet weight and hardness, and smooth, intact tablet surfaces.
[0095] Example 13 Preparation of decanoic acid haloperidol hydrochloride tablets
[0096] 1) Prescription (1000 tablets)
[0097]
[0098] 2) Preparation method: The prescribed amounts of decanoic acid haloperidol hydrochloride (crystal form B), microcrystalline cellulose, mannitol, anhydrous calcium hydrogen phosphate, and sodium dodecyl sulfate were placed in a three-dimensional mixer and mixed at 10 rpm for 20 minutes. Granulation was performed using a dry granulator, followed by the addition of magnesium stearate and mixing at 10 rpm for 5 minutes. Tableting was then performed. Results: The dry granulation and tableting processes were successful, resulting in stable tablet weight and hardness, and smooth, intact tablet surfaces.
[0099] As shown in Examples 5, 8, and 11, when using haloperidol decanoate as a raw material to prepare tablets, tableting is prone to sticking or softening during compression, resulting in unstable tablet hardness. Sticking is even more pronounced during dry granulation. As shown in Examples 6, 7, 9, 10, 12, and 13, when using haloperidol decanoate hydrochloride (crystal form A and crystal form B) prepared by the method of this invention as a raw material to prepare tablets, both dry granulation and tableting processes are smooth, with no sticking, and the compressed tablets have a smooth and intact surface.
[0100] Stability test
[0101] The samples from Examples 6, 7, 9, 10, 12, and 13 were respectively placed in oral solid pharmaceutical high-density polyethylene bottles and sealed with caps for accelerated stability testing to examine sample stability.
[0102] Experimental method: The samples were placed at a temperature of 40±2℃ and a relative humidity of 75±5% for 6 months. Samples were taken once each in the 0th, 1st, 2nd, 3rd and 6th months of the experiment. The content and total impurities were determined by high performance liquid chromatography. The results were compared with those of the 0th month. The comparison results are shown in Table 5.
[0103] Table 5. Comparison of Accelerated Test Results for Haloperidol Decanoate Hydrochloride Tablets
[0104]
[0105] The results in Table 5 show that, after 6 months of accelerated processing, the content of the samples prepared from decanoic acid haloperidol hydrochloride crystal form A (Examples 6, 9, and 12) did not decrease significantly, and the total impurities increased slightly, but the increase was small and within the allowable limits, indicating that the tablets prepared using decanoic acid haloperidol hydrochloride crystal form A prepared by the method of the present invention are of stable quality. However, after 6 months of accelerated processing, the content of the samples prepared from decanoic acid haloperidol hydrochloride crystal form B (Examples 7, 10, and 13) decreased significantly, and the total impurities increased significantly, indicating that the tablets prepared using decanoic acid haloperidol hydrochloride crystal form B are of unstable quality.
Claims
1. A crystalline form A of decanoic acid haloperidol hydrochloride, characterized in that: The X-ray powder diffraction pattern of crystal form A has characteristic peaks at 2θ values of 3.73°, 7.41°, 11.11°, 18.56°, 22.31°, 26.09°, and 29.89° ± 0.2°.
2. The X-ray powder diffraction pattern of crystal form A as described in claim 1 is shown in Figure 1.
3. A method for preparing crystal form A of claim 1, comprising dissolving decanoic acid haloperidol in solvent 1, stirring, slowly adding hydrochloric acid dropwise to the decanoic acid haloperidol solution, reacting at 10-30°C, filtering after the reaction is complete, and drying to obtain the product.
4. The method according to claim 3, wherein the volume-to-mass ratio of solvent 1 to decanoic acid haloperidol is (10:1)-(25:1) ml / g, preferably 20:1 ml / g.
5. The method according to claim 3 or 4, wherein the solvent 1 is selected from at least one of petroleum ether, isopropyl ether, methyl tert-butyl ether, methanol, ethanol, isopropanol, acetone, n-heptane, n-hexane, N,N-dimethylformamide, ethyl acetate, isopropyl acetate, tetrahydrofuran, and acetonitrile, preferably ethyl acetate.
6. The method according to claim 3, wherein the molar ratio of decanoic acid haloperidol to hydrochloric acid is (1:1.1)-(1:1.5).
7. The method according to claim 6, wherein the molar ratio of decanoic acid haloperidol to hydrochloric acid is 1:1.
3.
8. The method of claim 3, wherein the reaction is carried out at room temperature.
9. A pharmaceutical composition comprising crystal form A of claim 1 and pharmaceutically acceptable excipients.
10. The use of crystal form A of claim 1 or 2 in the manufacture of antipsychotic drugs.