A tolfenpyrad-salicylic acid-acetic acid ternary co-crystal

Abstract

This invention belongs to the field of crystalline drug molecular technology, and specifically relates to the field of topipirostat crystalline technology. Specifically, it describes a topipirostat-salicylic acid-acetic acid ternary cocrystal and its preparation method. In the cocrystal, the molar ratio of topipirostat, salicylic acid, and acetic acid is 1:1:1. Using Cu-Kα radiation, the X-ray diffraction pattern (represented by 2θ) shows characteristic peaks at 7.70±0.2°, 14.08±0.2°, 15.47±0.2°, 16.03±0.2°, 17.15±0.2°, 25.71±0.2°, and 26.64±0.2°. The topipirostat-salicylic acid-acetic acid ternary cocrystal prepared by this invention exhibits good solubility and stability, which is of great significance for improving the bioavailability of topipirostat and its formulation preparation.

Description

Technical Field

[0001] This invention belongs to the field of crystal drug molecule technology, specifically relating to a topiptostat-salicylic acid-acetic acid ternary eutectic. Background Technology

[0002] Topiroxostat, chemically named 4-[5-(pyridin-4-yl)-1H-[1,2,4]triazol-3-yl]pyridin-2-carboxylonitrile, was jointly developed by Sanwa Chemical Research Institute and Fuji Pharmaceutical in Japan. It was approved for marketing by the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan on June 28, 2013, under the brand names Uriadec or Topiloric. Topiroxostat is a non-purine selective xanthine oxidase inhibitor. Xanthine oxidase (XO) is an enzyme that produces reducing oxygen. XO catalyzes the oxidation of hypoxanthine to xanthine, and can also directly catalyze the oxidation of xanthine to uric acid. Topiroxostat reduces urea production in the body by inhibiting xanthine oxidase, making it suitable for the treatment of gout and hyperureaemia.

[0003] Topipustidine is a yellow crystalline powder, slightly soluble in N,N-dimethylformamide, sparingly soluble in 0.1 mol / L hydrochloric acid, very sparingly soluble in 99.5% ethanol and methanol, and practically insoluble in water, classifying it as a poorly soluble drug. This drug is marketed in tablet form. Due to its poor water solubility, it is difficult to achieve effective blood concentrations after oral administration, and the dosage is relatively large, causing severe gastrointestinal reactions and other toxic side effects. The structural formula of topipustidine is shown in Formula I below.

[0004]

[0005] For poorly soluble drugs, in addition to conventional formulation technologies such as formulation selection, micronization, solid dispersion, inclusion complex, and liposome technology, methods to improve dissolution can also be made by utilizing the polymorphic properties of drugs to change their crystal form and give them different lattice energies. This can fundamentally solve the bottleneck of low solubility and low dissolution rate of poorly soluble drugs, improve the drug's solubility, dissolution rate, bioavailability, and interaction with the target in vivo, and thus affect the efficacy of the drug.

[0006] Fuji Pharmaceutical Co., Ltd. of Japan first disclosed topipirostat and its synthetic route in CN1561340, and further disclosed two crystal forms (crystal form I and crystal form II) and a hydrate of topipirostat in WO2014014515. Crystal form I, which has slightly higher solubility and is the preferred crystal form in formulations, has a solubility of only 6.2 μg / mL in water. Furthermore, CN104042577 reported that crystal forms I and II interconvert during tableting, and this crystal form conversion has a potentially adverse effect on the dissolution and stability of the drug formulation. The low solubility, low dissolution rate, and the defect of crystal transformation in the preferred crystal form of topipirostat pose significant technical challenges in preparing solid dosage forms with good dissolution and stability.

[0007] CN104961730A discloses a new crystal form III of topiramate, CN105315260A discloses a crystal form of topiramate monohydrate and its preparation method, CN105693699A discloses a new crystal form A of topiramate and its preparation method, and CN110183424A discloses a crystal form A of topiramate and its preparation method. The solubility and dissolution rate of the obtained crystal forms still need to be improved.

[0008] Although numerous crystal forms of topipirostat have been published in existing literature, systematic research on these crystal forms still needs improvement, especially comprehensive studies on topipirostat cocrystal compounds. Novel drug cocrystal salts refer to supramolecular crystals with fixed stoichiometric ratios formed by the self-assembly of a new cocrystal material (CCF) with the active pharmaceutical ingredient (APT) under hydrogen bonding, introduced through proton transfer. Due to their potential advantages in dissolution, permeation, hygroscopicity, and stability, drug cocrystals have attracted increasing interest from researchers in the field of drug preparation. This invention provides a topipirostat-salicylic acid-acetic acid ternary cocrystal and its preparation method, providing better evidence for the application of topipirostat in drug therapy, thereby more effectively utilizing its medicinal value. Summary of the Invention

[0009] To address the shortcomings of existing technologies, the inventors conducted extensive experimental research, attempting to screen topiprostine with salicylic acid, malic acid, vanillic acid, taurine, tartaric acid, and other substances through co-crystal screening experiments. Ultimately, they successfully discovered the co-crystal of topiprostine and salicylic acid, which can effectively improve the solubility of topiprostine, providing a material basis for improving the oral absorption and bioavailability of topiprostine.

[0010] Another object of the present invention is to provide a preparation of a topipirostat-salicylic acid-acetic acid ternary eutectic as an active ingredient for the treatment of gout and hyperureemia.

[0011] The specific content of this invention is shown in Formula II below:

[0012]

[0013] In a first aspect, the present invention provides a ternary eutectic of topiprexate-salicylic acid-acetic acid as of Formula II, wherein the molar ratio of topiprexate, salicylic acid and acetic acid in the eutectic is 1:1:1.

[0014] Preferably, the topipsestat-salicylic acid-acetic acid ternary eutectic, when subjected to Cu-Kα radiation, exhibits characteristic peaks in its X-ray diffraction pattern (expressed as 2θ) at at least 7.70±0.2°, 14.08±0.2°, 15.47±0.2°, 16.03±0.2°, 17.15±0.2°, 25.71±0.2°, and 26.64±0.2°.

[0015] More preferably, the topipsestat-salicylic acid-acetic acid ternary eutectic, when subjected to Cu-Kα radiation, exhibits characteristic peaks in its X-ray diffraction pattern (expressed as 2θ) at at least 7.70±0.2°, 10.15±0.2°, 14.08±0.2°, 14.93±0.2°, 15.47±0.2°, 16.03±0.2°, 17.15±0.2°, 25.71±0.2°, 26.09±0.2°, and 26.64±0.2°.

[0016] More preferably, the topipsestat-salicylic acid-acetic acid ternary eutectic, when subjected to Cu-Kα radiation, exhibits characteristic peaks in its X-ray diffraction pattern (denoted as 2θ) at at least 7.00±0.2°, 7.70±0.2°, 8.19±0.2°, 10.15±0.2°, 12.32±0.2°, 14.08±0.2°, 14.93±0.2°, 15.47±0.2°, 16.03±0.2°, 17.15±0.2°, 21.05±0.2°, 25.71±0.2°, 26.09±0.2°, and 26.64±0.2°.

[0017] Preferably, the topipirostat-salicylic acid-acetic acid ternary eutectic, when subjected to Cu-Kα radiation, exhibits characteristic peaks consistent with those shown in the attached figure. Figure 1 The X-ray powder diffraction pattern shown is shown.

[0018] Preferably, the topipsestat-salicylic acid-acetic acid ternary eutectic has two endothermic peaks in the differential scanning calorimetry (DSC) curve, with corresponding temperature ranges and peak values ​​of 75.10–126.60℃ and a peak value of 112.77℃; and 157.20–225.65℃ and a peak value of 213.65℃.

[0019] Preferably, the topipirostat-salicylic acid-acetic acid ternary eutectic has the molecular formula C1. 22 H 18N6O5 has the following crystallographic parameters: triclinic crystal system, space group P-1; unit cell parameters are: α = 69.419(4)°, β = 86.104(4)°, γ = 76.449(4)°, cell volume

[0020] The ORTEP diagram of the topistat-salicylic acid-acetic acid ternary eutectic described in this invention is attached. Figure 2 As shown, this indicates that the eutectic is composed of one molecule of topipsestat combined with one molecule of salicylic acid and one molecule of acetic acid.

[0021] In a second aspect, the present invention provides a method for preparing the topipirostat-salicylic acid-acetic acid ternary eutectic, specifically comprising the following steps: dissolving topipirostat in acetic acid, dissolving salicylic acid in an organic solvent, then slowly adding the topipirostat acetic acid solution to the organic solvent of salicylic acid, heating and stirring until the solid is completely dissolved, filtering while hot to obtain a filtrate, evaporating the filtrate to crystallize at room temperature, filtering to obtain a solid, and drying under vacuum to obtain the topipirostat-salicylic acid-acetic acid ternary eutectic.

[0022] Preferably, the mass ratio of topipustrine to acetic acid is 1:0.12 to 0.2, with mass expressed in mg and volume in mL; more preferably, the mass ratio of topipustrine to organic solvent is 1:0.12 to 0.16.

[0023] Preferably, the molar ratio of topiptostat to salicylic acid is 1:1.02 to 1.75; more preferably, the molar ratio of topiptostat to salicylic acid is 1:1.02 to 1.25.

[0024] Preferably, the mass ratio of salicylic acid to organic solvent is 1:0.35 to 0.56, with mass expressed in mg and volume in mL; more preferably, the mass ratio of salicylic acid to organic solvent is 1:0.35 to 0.49.

[0025] Preferably, the organic solvent is methanol, ethanol, isopropanol, or acetone; more preferably, the organic solvent is methanol, ethanol, or isopropanol.

[0026] Preferably, the heating and stirring temperature is 50–60°C.

[0027] Preferably, the vacuum drying temperature is 30–45°C.

[0028] In one implementation, the following is included:

[0029] Topiprostine is soluble in acetic acid, and salicylic acid is soluble in methanol, ethanol, or isopropanol. The acetic acid solution of topiprostine is then slowly added to the aforementioned organic solvent containing salicylic acid. The mixture is heated and stirred at 50–60°C until completely dissolved. The solution is filtered while hot to obtain a filtrate. The filtrate is then evaporated and crystallized at room temperature. The solid is filtered to obtain a ternary eutectic of topiprostine-salicylic acid-acetic acid, which is then dried under vacuum at 30–45°C to obtain a ternary eutectic of topiprostine-salicylic acid-acetic acid. The molar ratio of topiprostine to salicylic acid is 1:1.02–1.15, and the mass ratio of topiprostine to acetic acid is 1:0.12–0.2. Mass is expressed in mg, and volume is expressed in mL.

[0030] In the preparation method provided by the present invention, the crude topiprostat raw material is commercially available topiprostat or topiprostat prepared by the present invention according to the prior art.

[0031] In a third aspect, the present invention provides a pharmaceutical composition comprising the aforementioned topipirostat-salicylic acid-acetic acid ternary eutectic and other pharmaceutically acceptable components.

[0032] Preferably, the method for preparing the pharmaceutical composition is as follows: using standard and conventional techniques, combining the compound of the present invention with a pharmaceutically acceptable solid or liquid carrier, and arbitrarily combining it with pharmaceutically acceptable excipients and formulation agents to prepare a usable dosage form.

[0033] Preferably, the available dosage form of the pharmaceutical composition is selected from tablets, capsules, powder for injection, or other pharmaceutically available dosage forms.

[0034] Confirmation of crystal structure

[0035] The topiptostat-salicylic acid-acetic acid ternary eutectic provided by this invention was subjected to X-ray single-crystal diffraction analysis.

[0036] The crystallographic data obtained from the testing and analysis of the topistat-salicylic acid-acetic acid ternary eutectic prepared in this invention are shown in Table 1. Its crystallographic parameters are: triclinic system, space group P-1; cell parameters are: α = 69.419(4)°, β = 86.104(4)°, γ = 76.449(4)°, cell volume The ORTEP diagram of the topistat-salicylic acid-acetic acid ternary eutectic described in this invention is attached. Figure 2 As shown, this indicates that the eutectic is composed of one molecule of topipsestat combined with one molecule of salicylic acid and one molecule of acetic acid.

[0037] Table 1. Main crystallographic data of the topitopate-salicylic acid-acetic acid ternary eutectic.

[0038]

[0039]

[0040] The X-ray powder diffraction testing instrument and conditions 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: PLXCEL; 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°. The structure is resolved using the direct method, and all non-hydrogen atoms are identified using the difference Fourier method. All hydrogen atoms on carbon and nitrogen are obtained through theoretical hydrogenation. The structure is refined using the least squares method. Based on the above crystallographic data, the characteristic peaks in the corresponding X-ray powder diffraction pattern (Cu-Kα) are detailed in the appendix. Figure 1 And Table 2.

[0041] Table 2. PXRD peaks of the topicoprolol-salicylic acid-acetic acid ternary eutectic

[0042]

[0043]

[0044] The TGA / DSC thermal analysis instrument and test conditions in this invention are as follows: TGA / DSC thermal analyzer: METTLERTOLED OGA / DSC3+ thermal analyzer, dynamic temperature range: 30~350℃; heating rate: 10℃ / min; program segment: gas N2; gas flow rate: 50mL / min; crucible: 40μL aluminum crucible.

[0045] The TGA / DSC test results of the topipirostat-salicylic acid-acetic acid ternary eutectic prepared by the method of the present invention are as follows: Figure 3 As shown, the DSC spectrum results indicate that the eutectic exhibits two endothermic melting peaks at approximately 112.77℃ and 213.65℃. The TGA results show that the eutectic possesses two weight loss steps. Therefore, the DSC / TGA results demonstrate that this invention successfully prepared a topipirostat-salicylic acid-acetic acid ternary eutectic.

[0046] Compared with the prior art, the technical effects achieved by the present invention are as follows:

[0047] 1. The topipirostat-salicylic acid-acetic acid ternary eutectic provided by the present invention has high solubility and stability, and is suitable for the preparation and long-term storage of pharmaceutical formulations;

[0048] 2. The preparation method provided by this invention has good reproducibility, is easy to operate, and has a high yield. Attached Figure Description

[0049] Figure 1X-ray powder diffraction pattern of the topiptostat-salicylic acid-acetic acid ternary eutectic;

[0050] Figure 2 ORTEP diagram of the ternary eutectic of topipusta-salicylic acid-acetic acid;

[0051] Figure 3 DSC-TGA image of the topiptostat-salicylic acid-acetic acid ternary eutectic. Detailed Implementation

[0052] 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.

[0053] Example 1

[0054] 24.9 mg of topiprotatine was dissolved in 3.0 mL of acetic acid, and 14.1 mg of salicylic acid was dissolved in 4.9 mL of isopropanol. The acetic acid solution of topiprotatine was then slowly added to the organic solvent of salicylic acid. The mixture was heated and stirred at 50 °C until completely dissolved. The solution was filtered while hot to obtain a filtrate. The filtrate was evaporated and crystallized at room temperature. The solid was filtered and placed in a small glass bottle, sealed with sealing film, and several holes were punched. The solid was allowed to evaporate, crystallize, and be filtered. The solid was dried under vacuum at 30 °C to obtain a ternary eutectic of topiprotatine-salicylic acid-acetic acid with a yield of 95.37% and a purity of 99.93%.

[0055] Example 2

[0056] 24.9 mg of topiprothiolane was dissolved in 3.5 mL of acetic acid, and 15.2 mg of salicylic acid was dissolved in 6.1 mL of methanol. The acetic acid solution of topiprothiolane was then slowly added to the organic solvent of salicylic acid. The mixture was heated and stirred at 55 °C until completely dissolved. The solution was filtered while hot to obtain a filtrate. The filtrate was evaporated and crystallized at room temperature. The solid was filtered to obtain a solid, which was placed in a small glass bottle, sealed with sealing film, and several holes were punched. The solid was allowed to evaporate, crystallize, and be filtered. The solid was dried under vacuum at 40 °C to obtain a ternary eutectic of topiprothiolane-salicylic acid-acetic acid with a yield of 96.46% and a purity of 99.95%.

[0057] Example 3

[0058] 24.9 mg of topiprotatine was dissolved in 4.0 mL of acetic acid, and 17.3 mg of salicylic acid was dissolved in 8.5 mL of ethanol. The acetic acid solution of topiprotatine was then slowly added to the organic solvent of salicylic acid. The mixture was heated and stirred at 60 °C until completely dissolved. The solution was filtered while hot to obtain a filtrate. The filtrate was evaporated and crystallized at room temperature. The solid was filtered to obtain a solid, which was placed in a small glass bottle, sealed with sealing film, and several holes were punched. The solid was then evaporated, crystallized, filtered, and dried under vacuum at 40 °C to obtain a ternary eutectic of topiprotatine-salicylic acid-acetic acid with a yield of 94.88% and a purity of 99.91%.

[0059] Example 4

[0060] 24.9 mg of topiprotatine was dissolved in 5.0 mL of acetic acid, and 24.2 mg of salicylic acid was dissolved in 13.6 mL of acetone. The acetic acid solution of topiprotatine was then slowly added to the organic solvent of salicylic acid. The mixture was heated and stirred at 50 °C until completely dissolved. The solution was filtered while hot to obtain a filtrate. The filtrate was evaporated and crystallized at room temperature. The solid was filtered and placed in a small glass bottle, sealed with sealing film, and several holes were punched. The solid was allowed to evaporate and crystallize. After filtration, the solid was dried under vacuum at 45 °C to obtain a ternary eutectic of topiprotatine-salicylic acid-acetic acid with a yield of 94.14% and a purity of 99.90%.

[0061] Example 5

[0062] 24.9 mg of topiprotatine was dissolved in 2.0 mL of acetic acid, and 13.8 mg of salicylic acid was dissolved in 4.8 mL of isopropanol. The acetic acid solution of topiprotatine was then slowly added to the organic solvent of salicylic acid. The mixture was heated and stirred at 50 °C until completely dissolved. The solution was filtered while hot to obtain a filtrate. The filtrate was evaporated and crystallized at room temperature. The solid was filtered and placed in a small glass bottle, sealed with sealing film, and several holes were punched. The solid was allowed to evaporate, crystallize, and be filtered. The solid was dried under vacuum at 30 °C to obtain a ternary eutectic of topiprotatine-salicylic acid-acetic acid with a yield of 85.46% and a purity of 98.97%.

[0063] Example 6

[0064] 24.9 mg of topiprotatine was dissolved in 6.2 mL of acetic acid, and 27.6 mg of salicylic acid was dissolved in 13.5 mL of isopropanol. The acetic acid solution of topiprotatine was then slowly added to the organic solvent of salicylic acid. The mixture was heated and stirred at 60 °C until completely dissolved. The solution was filtered while hot to obtain a filtrate. The filtrate was evaporated and crystallized at room temperature. The solid was filtered to obtain a solid, which was placed in a small glass bottle, sealed with sealing film, and several holes were punched. The solid was then evaporated, crystallized, filtered, and dried under vacuum at 40 °C to obtain a ternary eutectic of topiprotatine-salicylic acid-acetic acid with a yield of 84.13% and a purity of 98.94%.

[0065] Example 7

[0066] 24.9 mg of topiprotatine was dissolved in 5.0 mL of acetic acid, and 24.2 mg of salicylic acid was dissolved in 13.6 mL of tetrahydrofuran. The acetic acid solution of topiprotatine was then slowly added to the organic solvent of salicylic acid. The mixture was heated and stirred at 50 °C until completely dissolved. The solution was filtered while hot to obtain a filtrate. The filtrate was evaporated and crystallized at room temperature. The solid was filtered and placed in a small glass bottle, sealed with sealing film, and several holes were punched. The solid was allowed to evaporate, crystallize, and be filtered. The solid was dried under vacuum at 45 °C to obtain a ternary eutectic of topiprotatine-salicylic acid-acetic acid with a yield of 90.16% and a purity of 99.92%.

[0067] Example 8

[0068] 24.9 mg of topipustidine was added to a mixed solvent consisting of 5.0 mL of acetic acid, 24.2 mg of salicylic acid, 13.6 mL of acetone, and 10.9 mL of water. The mixture was heated under reflux until the solid was completely dissolved. After cooling and crystallization, the mixture was filtered and dried at room temperature overnight. No ternary eutectic of topipustidine-salicylic acid-acetic acid was obtained.

[0069] Solubility test

[0070] The ternary eutectic of topipsestat-salicylic acid-acetic acid obtained in the above examples has the same crystal form. The ternary eutectic of topipsestat-salicylic acid-acetic acid was prepared according to Examples 1 to 3, and its solubility and other properties were studied.

[0071] The solubility of the topipirostat-salicylic acid-acetic acid ternary eutectic obtained in Examples 1-3 in pH 6.5 phosphate buffer and pure water was determined. 10 mL of each medium (pH 6.5 phosphate buffer and pure water) was measured into vials, and excess sample was added to each. The vials were sealed and placed in a 25°C water bath with stirring for 24 hours. After filtration through a 0.45 μm filter membrane, the filtrate was analyzed by high-performance liquid chromatography (HPLC) to determine the sample content in the saturated solution. The results are shown in Table 3 below.

[0072] Table 3 shows the solubility of the obtained topiprostat-salicylic acid-acetic acid ternary eutectic in different pH buffer solutions.

[0073]

[0074] As shown in Table 3, the topipirostat-salicylic acid-acetic acid ternary eutectic prepared in this invention has good solubility, which helps to improve the bioavailability of topipirostat.

[0075] Stability test

[0076] The specific stability test methods were carried out in accordance with the guidelines for stability studies in Part IV of the 2015 edition of the Chinese Pharmacopoeia. Purity was determined by HPLC. The specific test results are shown in Table 4.

[0077] Table 4. Stability test results of the topiprostine-salicylic acid-acetic acid ternary eutectic under light, high temperature and high humidity conditions.

[0078]

[0079] As shown in Table 4, the total impurity content of the topipirostat-salicylic acid-acetic acid ternary eutectic prepared by the present invention did not change significantly under light, high temperature and high humidity conditions. This indicates that the topipirostat-salicylic acid-acetic acid ternary eutectic prepared by the present invention has high stability and is suitable for the manufacture and long-term storage of pharmaceutical preparations.

Claims

1. A topiptostat-salicylic acid-acetic acid ternary eutectic, characterized in that, In the eutectic, the molar ratio of topiprexate, salicylic acid, and acetic acid is 1:1:

1. The eutectic, when subjected to Cu-Kα radiation, exhibits characteristic peaks in its 2θ X-ray diffraction pattern at least at 7.70±0.2°, 14.08±0.2°, 15.47±0.2°, 16.03±0.2°, 17.15±0.2°, 25.71±0.2°, and 26.64±0.2°. The preparation method of the eutectic specifically includes the following steps: dissolving topiprexate in acetic acid and salicylic acid in an organic solvent; then slowly adding the topiprexate acetic acid solution to the salicylic acid organic solvent, heating and stirring until solid. The solid is completely dissolved, filtered while hot to obtain a filtrate, and the filtrate is evaporated and crystallized at room temperature. The solid is then filtered and dried under vacuum to obtain a ternary eutectic of topiprexate, salicylic acid, and acetic acid. The molar ratio of topiprexate to salicylic acid is 1:1.02~1.75, and the mass ratio of topiprexate to acetic acid is 1:0.12~0.2, where the mass is in mg and the volume is in mL. The organic solvent is methanol, ethanol, isopropanol, or acetone, and the mass ratio of salicylic acid to the organic solvent is 1:0.35~0.56, where the mass is in mg and the volume is in mL. The heating and stirring temperature is 50~60℃.

2. The eutectic according to claim 1, characterized in that, Using Cu-Kα radiation, the X-ray diffraction pattern, expressed as 2θ, has characteristic peaks at at least 7.70±0.2°, 10.15±0.2°, 14.08±0.2°, 14.93±0.2°, 15.47±0.2°, 16.03±0.2°, 17.15±0.2°, 25.71±0.2°, 26.09±0.2°, and 26.64±0.2°.

3. The eutectic according to claim 1, characterized in that, Using Cu-Kα radiation, its characteristic peaks conform to the X-ray powder diffraction pattern shown in Figure 1.

4. The eutectic according to claim 1, characterized in that, Its molecular formula is C 22 H 18 N6O5 has the following crystallographic parameters: triclinic system, space group P-1; cell parameters: a=7.9892(4)Å, b=10.9101(5)Å, c=13.4568(6)Å, α=69.419(4) °, β=86.104(4) °, γ=76.449(4) °, and cell volume V=1067.37(9)Å3.

Images