Zolpidem co-crystals and methods of making the same

Abstract

The present application relates to the technical field of crystal form drug molecules, and specifically provides a zolpidem co-crystal and a preparation method thereof.The present application specifically provides a co-crystal of zolpidem and succinic acid with a molar ratio of 2:1 and a co-crystal of zolpidem and glutaric acid with a molar ratio of 2:1.The preparation method of the zolpidem co-crystal provided by the present application is simple in operation, the prepared crystal has high purity, the zolpidem co-crystal provided by the present application has good chemical stability and good solubility.

Description

Technical Field

[0001] This invention relates to the field of crystal form drug molecule technology, and particularly to the field of zolpidem crystal form technology, specifically zolpidem cocrystal, its preparation method and application. Background Technology

[0002] Zolpidem, chemical name: N,N,6-trimethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine-3-acetamide, CAS number: 82626-48-0, its structural formula is shown below:

[0003]

[0004] Zolpidem is a non-benzodiazepine imidazopyridine short-acting sedative-hypnotic drug developed by Sanofi, France. It was first marketed in 1988 for the treatment of insomnia and brain disorders. Clinical trials have shown that zolpidem, as a new generation of hypnotics, is highly selective, has a short half-life (lasting only 1.6 hours), no rebound effect after discontinuation, few side effects, and no respiratory depression, making it one of the most popular sedative-hypnotic drugs currently available.

[0005] Currently, the main marketed zolpidem product is zolpidem tartrate. However, known zolpidem tartrate salts exhibit polymorphism (A, B, C, D, E, F, G, and H crystal forms), and these polymorphs can transform into each other under certain conditions. Therefore, preparing cocrystals or salts of zolpidem with similar pharmacodynamic effects can effectively avoid the instability caused by polymorphic transformation of zolpidem.

[0006] This invention provides a simple and easy-to-operate method for preparing high-purity zolpidem cocrystals, providing a better basis for the application of zolpidem in drug therapy, thereby maximizing the medicinal value of zolpidem. Summary of the Invention

[0007] In view of the shortcomings of the prior art, the present invention provides a zolpidem cocrystal, a method for preparing the cocrystal, and its application.

[0008] In a first aspect, the present invention provides a zolpidem cocrystal, said cocrystal being formed by combining zolpidem and a cocrystal forming agent, wherein the cocrystal forming agent is selected from succinic acid and glutaric acid.

[0009] The zolpidem cocrystal described in this article is either a zolpidem-succinic acid cocrystal or a zolpidem-glutaric acid cocrystal.

[0010] Zolpidem-succinic acid cocrystal

[0011] In one embodiment, the present invention relates to a cocrystal formed by combining zolpidem and succinic acid, specifically a cocrystal formed by zolpidem and succinic acid in a molar ratio of 2:1.

[0012] Zolpidem-succinic acid eutectic can be characterized by having one or more of the following physical characteristics:

[0013] The zolpidem-succinic acid eutectic described in this invention exhibits characteristic peaks at 8.26±0.2°, 9.82±0.2°, 10.60±0.2°, 19.60±0.2°, 20.05±0.2°, and 21.89±0.2° in its X-ray diffraction pattern (denoted as 2θ) under Cu-Kα radiation.

[0014] Preferably, the zolpidem-succinic acid eutectic, when subjected to Cu-Kα radiation, exhibits characteristic peaks in its 2θ X-ray diffraction pattern at 8.26±0.2°, 9.82±0.2°, 10.60±0.2°, 15.59±0.2°, 15.76±0.2°, 18.13±0.2°, 19.60±0.2°, 20.05±0.2°, 21.17±0.2°, 21.89±0.2°, 23.02±0.2°, 26.93±0.2°, 31.56±0.2°, and 34.54±0.2°.

[0015] Preferably, the zolpidem-succinic acid eutectic, when subjected to Cu-Kα radiation, exhibits characteristic peaks that conform to... Figure 1 The X-ray powder diffraction pattern shown is shown.

[0016] Preferably, the zolpidem-succinic acid cocrystal, when subjected to Cu-Kα radiation, exhibits characteristic peaks consistent with the detection data shown in Table 3.

[0017] Preferably, the zolpidem-succinic acid eutectic exhibits an endothermic peak in the range of 171.14℃ to 203.22℃ as detected by differential scanning calorimetry (DSC).

[0018] The zolpidem-succinic acid eutectic has the following crystallographic parameters: monoclinic crystal system, chiral space group P21 / c; and cell parameters: α = 90.00°, β = 90.752(2)°, γ = 90.00°, cell volume

[0019] Zolpidem-Glutaric Acid Cocrystal

[0020] In one embodiment, the present invention relates to a cocrystal formed by combining zolpidem and glutaric acid, specifically a cocrystal formed by zolpidem and glutaric acid in a molar ratio of 2:1.

[0021] Zolpidem-glutaric acid eutectic crystals can be characterized by having one or more of the following physical characteristics:

[0022] The zolpidem-glutaric acid cocrystal of the present invention, when subjected to Cu-Kα radiation, exhibits characteristic peaks at 6.98±0.2°, 8.81±0.2°, 9.38±0.2°, 9.51±0.2°, and 10.76±0.2° in its X-ray diffraction pattern (denoted as 2θ).

[0023] Preferably, the zolpidem-glutaric acid eutectic crystal, when subjected to Cu-Kα radiation, exhibits characteristic peaks in its 2θ X-ray diffraction pattern at 6.98±0.2°, 8.81±0.2°, 9.08±0.2°, 9.38±0.2°, 9.51±0.2°, 10.76±0.2°, 15.02±0.2°, 18.69±0.2°, 19.07±0.2°, 19.48±0.2°, 19.73±0.2°, 21.27±0.2°, 21.64±0.2°, 23.62±0.2°, 24.18±0.2°, and 29.21±0.2°.

[0024] Preferably, the zolpidem-glutaric acid eutectic crystal, when subjected to Cu-Kα radiation, exhibits characteristic peaks that conform to... Figure 5 The X-ray powder diffraction pattern shown is shown.

[0025] Preferably, the zolpidem-glutaric acid cocrystal, when subjected to Cu-Kα radiation, exhibits characteristic peaks consistent with the detection data shown in Table 4.

[0026] Preferably, the zolpidem-glutaric acid eutectic crystal exhibits an endothermic peak within the range of 142.22℃ to 167.06℃ as detected by differential scanning calorimetry (DSC), with a peak value of 157.22℃, which corresponds to the melting point of the zolpidem-glutaric acid eutectic crystal.

[0027] The crystallographic parameters of the zolpidem-glutaric acid eutectic are: monoclinic system, space group P21 / n; cell parameters are: α = 90.00°, β = 90.4827(9)°, γ = 90.00°, cell volume

[0028] In a second aspect, the present invention provides a method for preparing the zolpidem cocrystal.

[0029] The zolpidem cocrystal of this invention can be prepared by the following method: dissolving zolpidem and the cocrystal formation in an organic solvent, heating to dissolve, clarifying the solution, cooling to crystallize, filtering, and drying to obtain the zolpidem cocrystal. The specific preparation method is as follows:

[0030] The zolpidem-succinic acid cocrystal of the present invention can be prepared by the following method: for example, zolpidem and succinic acid are dissolved in organic solvent A, heated to dissolve, the solution is clarified, cooled to crystallize, filtered, the filter cake is washed, and dried to obtain zolpidem-succinic acid cocrystal.

[0031] The zolpidem-glutaric acid cocrystal of the present invention can be prepared by the following method: for example, zolpidem and glutaric acid are dissolved in organic solvent A, heated to dissolve, the solution is clarified, cooled to crystallize, filtered, the filter cake is washed, and dried to obtain zolpidem-glutaric acid cocrystal.

[0032] The organic solvent A is selected from one or a mixture of at least two of acetone, methanol, ethanol, and acetonitrile.

[0033] Preferably, the organic solvent A is selected from one or a mixture of two of acetone, methanol, and acetonitrile.

[0034] The molar ratio of zolpidem to the eutectic formation is 1:0.5 to 2.0; preferably, the molar ratio of zolpidem to the eutectic formation is 1:0.5 to 0.8.

[0035] The mass-to-volume ratio of succinic acid and organic solvent A in the system is 12:1 to 8, where mass is expressed in mg and volume in ml.

[0036] Preferably, the mass-to-volume ratio of succinic acid to organic solvent A in the system is 12:4 to 6, where the mass is expressed in mg and the volume in ml.

[0037] The mass-to-volume ratio of glutaric acid and organic solvent A in the system is 26:1 to 8, where mass is expressed in mg and volume in ml.

[0038] Preferably, the mass-to-volume ratio of glutaric acid and organic solvent A in the system is 26:4 to 6, where the mass is expressed in mg and the volume in ml.

[0039] The volume ratio of acetone to organic solvent A in the system is 0.4 to 0.6:1.

[0040] The melting and heating temperature is 40–55°C.

[0041] The cooling crystallization temperature is 0–30°C, preferably 15–25°C.

[0042] The crystallization time is 4 to 6 hours.

[0043] The drying temperature is 45–70°C, and the drying time is 8–12 hours.

[0044] The solvent for washing the filter cake is selected from acetone, methanol, ethanol, and acetonitrile.

[0045] A third aspect of the present invention provides a pharmaceutical composition comprising the zolpidem-succinic acid cocrystal or zolpidem-glutaric acid cocrystal described herein, and containing other active ingredients that may be used in combination and / or pharmaceutically acceptable excipient components.

[0046] Preferably, the other components include other active ingredients, excipients, fillers, etc., that can be used in combination.

[0047] Preferably, the pharmaceutical composition can be formulated into sprays, tablets, capsules, powder injections, liquid injections, etc., using standard and conventional techniques.

[0048] In a fourth aspect, the invention provides the application of zolpidem-succinic acid cocrystal or zolpidem-glutaric acid cocrystal as active ingredients in the preparation of sedative-hypnotic drugs.

[0049] Crystal structure confirmed

[0050] (1) X-ray single crystal diffraction test

[0051] The X-ray single-crystal diffraction instrument and testing conditions used for the zolpidem cocrystal of this invention are as follows: X-ray crystal data were collected on a Rigaku XtaLAB Synergy instrument in Japan, the testing temperature was 293(2) K, CuKa radiation was used, data were collected in ω-scan mode and Lp correction was performed. The structure was resolved by direct method, all non-hydrogen atoms were identified by difference Fourier method, all hydrogen atoms on carbon and nitrogen were obtained by theoretical hydrogenation, and the structure was refined by least squares method.

[0052] The crystallographic data of the zolpidem-succinic acid eutectic prepared in this invention were tested and analyzed. Its crystallographic parameters are: monoclinic system, chiral space group P21 / c; cell parameters are: α = 90.00°, β = 90.752(2)°, γ = 90.00°, cell volume The molecular formula is: C 42 H 48 N6O6, molecular weight: 732.86. See Table 1 for details.

[0053] Table 1. Main crystallographic data of zolpidem-succinic acid cocrystal

[0054]

[0055]

[0056] The structural analysis photograph of the zolpidem-succinic acid eutectic described in this invention shows that the crystal contains two molecules of zolpidem and one molecule of succinic acid, as shown in the image. Figure 3 As shown. The packing diagram of the zolpidem-succinic acid eutectic of the present invention is as follows. Figure 2 As shown.

[0057] The crystallographic data obtained from the zolpidem-glutaric acid eutectic prepared in this invention were tested and analyzed. Its crystallographic parameters are: monoclinic system, space group P21 / n; cell parameters are: α = 90.00°, β = 90.4827(9)°, γ = 90.00°, cell volume The molecular formula is: C 43 H 50 N6O6, molecular weight: 746.89. See Table 2 for details.

[0058] Table 2. Main crystallographic data of zolpidem-glutaric acid cocrystal

[0059]

[0060]

[0061] The structural analysis photograph of the zolpidem-glutaric acid eutectic of the present invention shows that the crystal contains two molecules of zolpidem and one molecule of glutaric acid, as shown in the following figure. Figure 7 As shown. The packing diagram of the zolpidem-glutaric acid eutectic of the present invention is as follows. Figure 6 As shown.

[0062] (2) X-ray powder diffraction detection

[0063] The X-ray powder diffraction testing instrument and conditions used for the zolpidem cocrystal described in this invention are as follows: PANalytical Empyrean X-ray powder diffractometer; light source Cu target, flat sample stage, incident light path: BBHD, diffraction light path: PIXCEL, voltage 45KV, current 40mA, divergence slit 1 / 4°, anti-scattering slit 1°, Solar slit 0.04rad, counting time per step 0.5s, scanning range 3~50°.

[0064] The main X-ray powder diffraction characteristic peaks of the zolpidem-succinic acid eutectic are shown in Table 3.

[0065] Table 3. Main PXRD peaks of zolpidem-succinic acid cocrystal

[0066]

[0067]

[0068] The main X-ray powder diffraction characteristic peaks of the zolpidem-glutaric acid eutectic are shown in Table 4.

[0069] Table 4. Major PXRD peaks of zolpidem-glutaric acid cocrystal

[0070]

[0071] All samples prepared in the examples have the same crystallographic parameters and X-ray powder diffraction patterns as described above.

[0072] (3) TGA / DSC analysis

[0073] The TGA / DSC thermal analysis instrument and test conditions used for the zolpidem cocrystal of this invention are as follows: TGA / DSC thermal analyzer: METTLER TOLEDO TGA / DSC3+; dynamic temperature range: 30~300℃; heating rate: 10℃ / min; programmed gas N2; gas flow rate: 50mL / min; crucible: 40μl aluminum crucible.

[0074] The differential scanning calorimetry (DSC) results of the zolpidem-succinic acid cocrystal prepared by the method of the present invention are shown in Figure 4. The zolpidem-succinic acid cocrystal exhibits an endothermic peak within the temperature range of 171.14℃ to 203.22℃, with an initial temperature of 183.67℃, corresponding to the melting point of the zolpidem-succinic acid cocrystal. The zolpidem-succinic acid cocrystal possesses the following characteristics: Figure 4 The DSC / TGA spectrum shown.

[0075] The differential scanning calorimetry (DSC) results of the zolpidem-glutaric acid cocrystal prepared by the method described herein are shown in Figure 8. The zolpidem-glutaric acid cocrystal, as detected by DSC, exhibits an endothermic peak within the temperature range of 142.22℃ to 167.06℃, with a peak value of 157.22℃, corresponding to the melting point of the zolpidem-glutaric acid cocrystal. The zolpidem-glutaric acid cocrystal possesses the following characteristics: Figure 8 The DSC / TGA spectrum shown.

[0076] The method for preparing zolpidem cocrystals provided by this invention is simple to operate, and the prepared crystals have high purity. The zolpidem cocrystals provided by this invention have good chemical stability and good solubility. Attached Figure Description

[0077] Figure 1 X-ray powder diffraction pattern of zolpidem-succinic acid eutectic

[0078] Figure 2 Packing diagram of zolpidem-succinic acid eutectic

[0079] Figure 3 ORTEP diagram of zolpidem-succinic acid cocrystal

[0080] Figure 4 Differential scanning calorimetry (DSC) curves of zolpidem-succinic acid eutectic

[0081] Figure 5 X-ray powder diffraction pattern of zolpidem-glutaric acid eutectic

[0082] Figure 6 Packing diagram of zolpidem-glutaric acid eutectic

[0083] Figure 7 ORTEP diagram of zolpidem-glutaric acid cocrystal

[0084] Figure 8 Differential scanning calorimetry (DSC) curves of zolpidem-glutaric acid eutectic Detailed implementation method:

[0085] The present invention will be further illustrated by the following embodiments. It should be understood that the embodiments of the present invention are merely for illustrating the present invention and are not intended to limit the present invention. Therefore, any simple improvements to the present invention under the premise of the method of the present invention are within the scope of protection claimed by the present invention.

[0086] Preparation of zolpidem-succinic acid eutectic

[0087] Example 1

[0088] 307.5 mg of zolpidem and 65 mg of succinic acid were added to 22 mL of a mixed solvent (11 mL of methanol and 11 mL of acetone), heated to 50 °C and stirred to dissolve. The mixture was refluxed for 1 hour, then slowly cooled to 15–25 °C and allowed to stand for crystallization for 4 hours. The crystals were filtered, the filter cake was washed with ethanol, and dried under vacuum at 50 °C for 8 hours to obtain zolpidem-succinic acid cocrystals with a yield of 93.56% and a purity of 99.95%.

[0089] Example 2

[0090] 200 mg of zolpidem and 54 mg of succinic acid were added to 27 mL of a mixed solvent (11 mL of acetonitrile and 16 mL of acetone), heated to 55 °C and stirred to dissolve. The mixture was refluxed for 1 hour, then slowly cooled to 14–23 °C and allowed to stand for 6 hours to crystallize. The crystals were filtered, the filter cake was washed with methanol, and dried under vacuum at 60 °C for 10 hours to obtain zolpidem-succinic acid cocrystals with a yield of 92.15% and a purity of 99.94%.

[0091] Example 3

[0092] 100.5 mg of zolpidem and 31 mg of succinic acid were added to 10 mL of a mixed solvent (6 mL of ethanol and 4 mL of acetone), heated to 52 °C and stirred to dissolve. The mixture was refluxed for 2 hours, then slowly cooled to 10–20 °C and allowed to stand for crystallization for 4 hours. The crystals were filtered, washed with acetonitrile, and dried under vacuum at 55 °C for 12 hours to obtain zolpidem-succinic acid cocrystals with a yield of 91.89% and a purity of 99.93%.

[0093] Example 4

[0094] 89.5 mg of zolpidem and 34 mg of succinic acid were added to 20 mL of a mixed solvent (11 mL of ethanol and 9 mL of acetone), heated to 45 °C and stirred to dissolve. The mixture was refluxed for 1 hour, then slowly cooled to 18–27 °C and allowed to stand for crystallization for 5 hours. The crystals were filtered, the filter cake was washed with acetone, and dried under vacuum at 65 °C for 9 hours to obtain zolpidem-succinic acid cocrystals with a yield of 91.81% and a purity of 99.87%.

[0095] Example 5

[0096] 153 mg of zolpidem and 118 mg of succinic acid were added to 78 mL of a mixed solvent (39 mL of methanol and 39 mL of acetone), heated to 40 °C and stirred to dissolve. The mixture was refluxed for 2 hours, then slowly cooled to 20–30 °C and allowed to stand for 6 hours to crystallize. The crystals were filtered, the filter cake was washed with acetone, and dried under vacuum at 70 °C for 9 hours to obtain zolpidem-succinic acid cocrystals with a yield of 91.59% and a purity of 99.71%.

[0097] Example 6

[0098] 123 mg of zolpidem and 118 mg of succinic acid were added to 98 mL of a mixed solvent (24.5 mL of methanol, 24.5 mL of acetonitrile, and 49 mL of acetone). The mixture was heated to 50 °C and stirred to dissolve. The mixture was refluxed for 1 hour, then slowly cooled to 0–10 °C and allowed to stand for crystallization for 3 hours. The crystals were filtered, the filter cake was washed with ethanol, and dried under vacuum at 75 °C for 13 hours to obtain zolpidem-succinic acid cocrystals with a yield of 76.14% and a purity of 97.53%.

[0099] Example 7

[0100] 224 mg of zolpidem and 34.5 mg of succinic acid were added to 14.5 mL of mixed solvent (7 mL of acetonitrile and 7.5 mL of acetone), heated to 35 °C and stirred to dissolve. The mixture was refluxed for 1 hour, then slowly cooled to 25–35 °C and allowed to stand for crystallization for 7 hours. The crystals were filtered, the filter cake was washed with methanol, and dried under vacuum at 40 °C for 7 hours to obtain zolpidem-succinic acid cocrystals with a yield of 71.53% and a purity of 98.47%.

[0101] Preparation of zolpidem-glutaric acid eutectic

[0102] Example 8

[0103] 201 mg of zolpidem and 43 mg of glutaric acid were added to 8 mL of a mixed solvent (4 mL of methanol and 4 mL of acetone), heated to 50 °C and stirred to dissolve. The mixture was refluxed for 1 hour, then slowly cooled to 17–25 °C and allowed to stand for 4 hours to crystallize. The crystals were filtered, the filter cake was washed with ethanol, and dried under vacuum at 50 °C for 8 hours to obtain zolpidem-glutaric acid cocrystals with a yield of 92.06% and a purity of 99.90%.

[0104] Example 9

[0105] 134 mg of zolpidem and 34 mg of glutaric acid were added to 5 mL of mixed solvent (2 mL of ethanol and 3 mL of acetone), heated to 40 °C and stirred to dissolve. The mixture was refluxed for 1 hour, then slowly cooled to 10–18 °C and allowed to stand for 6 hours to crystallize. The crystals were filtered, the filter cake was washed with methanol, and dried under vacuum at 45 °C for 12 hours to obtain zolpidem-glutaric acid cocrystals with a yield of 91.78% and a purity of 99.87%.

[0106] Example 10

[0107] 60.5 mg of zolpidem and 21 mg of glutaric acid were added to 5 mL of a mixed solvent (3 mL of acetonitrile and 2 mL of acetone), heated to 55 °C and stirred to dissolve. The mixture was refluxed for 2 hours, then slowly cooled to 15–23 °C and allowed to stand for crystallization for 5 hours. The crystals were filtered, the filter cake was washed with acetonitrile, and dried under vacuum at 65 °C for 10 hours to obtain zolpidem-glutaric acid cocrystals with a yield of 91.32% and a purity of 99.85%.

[0108] Example 11

[0109] 189.5 mg of zolpidem and 163 mg of glutaric acid were added to 19 mL of a mixed solvent (9.5 mL of methanol and 9.5 mL of acetone), heated to 53 °C and stirred to dissolve. The mixture was refluxed for 2 hours, then slowly cooled to 23–30 °C and allowed to stand for crystallization for 6 hours. The crystals were filtered, washed with acetonitrile, and dried under vacuum at 70 °C for 10 hours to obtain zolpidem-glutaric acid cocrystals with a yield of 90.10% and a purity of 99.81%.

[0110] Example 12

[0111] 315 mg of zolpidem and 406 mg of glutaric acid were added to 31 mL of a mixed solvent (15.5 mL of ethanol and 15.5 mL of acetone), heated to 35 °C and stirred to dissolve. The mixture was refluxed for 2 hours, then slowly cooled to 27–35 °C and allowed to stand for crystallization for 7 hours. The crystals were filtered, the filter cake was washed with methanol, and dried under vacuum at 75 °C for 13 hours to obtain zolpidem-glutaric acid cocrystals with a yield of 90.05% and a purity of 97.63%.

[0112] Example 13

[0113] 300 mg of zolpidem and 58 mg of glutaric acid were added to 20 mL of a mixed solvent (10 mL of acetonitrile and 10 mL of acetone), heated to 55 °C and stirred to dissolve. The mixture was refluxed for 2 hours, then slowly cooled to 6–14 °C and allowed to stand for crystallization for 3 hours. The crystals were filtered, the filter cake was washed with ethanol, and dried under vacuum at 35 °C for 7 hours to obtain zolpidem-glutaric acid cocrystals with a yield of 86.42% and a purity of 98.56%.

[0114] Stability test

[0115] The zolpidem cocrystals prepared in Examples 1 and 8 of this invention were subjected to accelerated testing and placed in a constant temperature and humidity incubator at 40±2℃ and RH 75±5% for 6 months. Samples were taken at the end of 1, 2, 3, and 6 months to test appearance, related substances, and purity. The results are shown in Table 5.

[0116] Table 5. Accelerated test results of zolpidem cocrystal

[0117]

[0118] Accelerated testing showed that the zolpidem cocrystal of the present invention has relatively stable physicochemical properties, and the purity of the zolpidem cocrystal did not decrease significantly, while the increase in impurity content was minimal.

[0119] Solubility test

[0120] For specific solubility tests, in accordance with the Chinese Pharmacopoeia 2015, excess amounts of zolpidem cocrystals from Examples 1 and 8 were accurately weighed and placed in small vials. Hydrochloric acid solution (pH 1.0) and water were added respectively to prepare saturated zolpidem cocrystal solutions. The solutions were then shaken to dissolve and filtered. The solubility was calculated by measuring the absorbance at a wavelength of 270 nm using ultraviolet-visible spectrophotometry (General Rule 0401). The test results are shown in Table 6.

[0121] Table 6 Solubility of zolpidem cocrystal

[0122]

[0123] Experiments have shown that all zolpidem cocrystals prepared according to the present invention can achieve similar solubility effects and have good solubility.

Claims

1. Zolpidem cocrystal, characterized in that, The eutectic is formed by combining zolpidem and a eutectic formation, wherein the eutectic formation is selected from glutaric acid; the zolpidem-glutaric acid eutectic is formed by combining zolpidem and glutaric acid in a molar ratio of 2:1; using Cu-Kα radiation, the X-ray diffraction pattern, expressed in 2θ, has characteristic peaks at 6.98±0.2°, 8.81±0.2°, 9.38±0.2°, 9.51±0.2°, and 10.76±0.2°.

2. The zolpidem cocrystal as described in claim 1, characterized in that, The eutectic is selected from the following eutectic types: Zolpidem-glutaric acid cocrystal, when irradiated with Cu-Kα, exhibits characteristic peaks consistent with the X-ray powder diffraction pattern shown in Figure 5 or the detection data shown in Table 4.

3. The method for preparing zolpidem cocrystal according to any one of claims 1-2, characterized in that, The preparation of the zolpidem co-crystal includes the following steps: Zolpidem and glutaric acid are dissolved in organic solvent A, heated to dissolve, and after the solution becomes clear, it is cooled to crystallize, filtered, the filter cake is washed, and dried to obtain zolpidem-glutaric acid cocrystals; wherein the organic solvent A is selected from one or a mixture of at least two of acetone, methanol, ethanol, and acetonitrile.

4. The method for preparing zolpidem cocrystal as described in claim 3, characterized in that, The molar ratio of zolpidem to the eutectic formation is 1:0.5 to 2.

0.

5. A pharmaceutical composition, characterized in that, It comprises zolpidem cocrystal as described in any one of claims 1 to 2, and contains other active ingredients that can be used in combination and / or pharmaceutically acceptable excipient components.

6. The use of the zolpidem cocrystal as an active ingredient in the preparation of sedative-hypnotic drugs according to claims 1-2.

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