Development of new multicomponent crystals of the antifungal drug tioconazole and the assessment of their biopharmaceutical attributes
Madhesiya, Avinash; Dash, Sibananda G.; Gupta, Princi; Akhir, Abdul; Saxena, Deepanshi; Maitra, Rahul; Chopra, Sidharth; Thakur, Tejender S.; CrystEngComm 25 (2023) 6758–6776; doi:10.1039/D3CE00948C

data_7247719
_publ_section_title
;
 Development of new multicomponent crystals of the antifungal drug
 tioconazole and the assessment of their biopharmaceutical attributes
;
_journal_issue                   48
_journal_name_full               CrystEngComm
_journal_page_first              6758
_journal_page_last               6776
_journal_paper_doi               10.1039/D3CE00948C
_journal_volume                  25
_journal_year                    2023
_chemical_formula_moiety
'C16 H14 Cl3 N2 O S, C4 H5 O6, 3(H2 O), 0.42(O)'
_chemical_formula_sum            'C20 H25 Cl3 N2 O10.42 S'
_chemical_formula_weight         598.57
_chemical_name_common            'Tioconazole-L-tartrate 1:1 salt hydrate'
_space_group_crystal_system      orthorhombic
_space_group_IT_number           19
_space_group_name_Hall           'P 2ac 2ab'
_space_group_name_H-M_alt        'P 21 21 21'
_atom_sites_solution_hydrogens   mixed
_audit_creation_method           SHELXL-2019/2
_audit_update_record
;
2023-09-21 deposited with the CCDC.	2023-11-14 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   7.60280(10)
_cell_length_b                   9.94440(10)
_cell_length_c                   35.6016(4)
_cell_measurement_reflns_used    54997
_cell_measurement_temperature    293(2)
_cell_measurement_theta_max      76.6930
_cell_measurement_theta_min      2.4770
_cell_volume                     2691.67(5)
_computing_cell_refinement       'CrysAlisPro 1.171.42.88a (Rigaku OD, 2023)'
_computing_data_collection       'CrysAlisPro 1.171.42.88a (Rigaku OD, 2023)'
_computing_data_reduction        'CrysAlisPro 1.171.42.88a (Rigaku OD, 2023)'
_computing_structure_refinement  'SHELXL-2019/2 (Sheldrick, 2019)'
_computing_structure_solution    'SHELXL-2018/2 (Sheldrick, 2015)'
_diffrn_ambient_temperature      293(2)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            HyPix
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.987
_diffrn_measurement_details
;
List of Runs (angles in degrees, time in seconds):

  # Type    Start    End  Width  t~exp~   \w     \q     \k     \f   Frames
  1  \w    -19.00  22.00   0.50    0.05    --   14.00 100.00-175.98   82
  2  \w      2.00  43.00   0.50    0.05    --   30.00  88.00 -80.38   82
  3  \w    -20.00   7.00   0.50    0.05    --   14.00 103.00 -20.34   54
  4  \w      0.00  34.00   0.50    0.05    --   30.00  93.00 115.73   68
  5  \w     13.00  42.00   0.50    0.05    --   42.00  91.00  12.02   58
  6  \w     14.00  43.00   0.50    0.05    --   42.00  88.00  87.55   58
  7  \w     25.00 119.00   0.50    0.05    --   47.33  77.00 120.00  188
  8  \w     35.00 122.00   0.50    0.05    --   47.33  19.00 150.00  174
  9  \w     32.00 126.00   0.50    0.05    --   54.00  75.00  33.66  188
 10  \w     44.00 139.00   0.50    0.05    --   66.00  75.00 -25.96  190
 11  \w     44.00 139.00   0.50    0.05    --   66.00  76.00 -69.39  190
 12  \w     25.00 119.00   0.50    0.05    --   47.33  77.00-150.00  188
 13  \w     33.00 126.00   0.50    0.05    --   54.00  74.00-127.64  186
 14  \w     38.00 131.00   0.50    0.05    --   58.00  71.00 -99.18  186
 15  \w     44.00 139.00   0.50    0.05    --   66.00  76.00 -69.39  190
 16  \w    120.00 174.00   0.50    0.22    --  109.61 125.00 -30.00  108
 17  \w    107.00 178.00   0.50    0.22    --  109.61 101.00   4.00  142
 18  \w     38.00  63.00   0.50    0.22    --  109.61 -57.00  30.00   50
 19  \w     38.00  63.00   0.50    0.22    --  109.61 -57.00  60.00   50
 20  \w     38.00  63.00   0.50    0.22    --  109.61 -57.00 120.00   50
 21  \w     40.00 106.00   0.50    0.22    --  109.61-125.00 120.00  132
 22  \w     41.00 109.00   0.50    0.22    --  109.61-125.00 150.00  136
 23  \w     77.00 108.00   0.50    0.22    --  109.61-125.00 -30.00   62
 24  \w     81.00 106.00   0.50    0.22    --  109.61 -99.00 -30.00   50
 25  \w     40.00  68.00   0.50    0.22    --  109.61-125.00 -30.00   56
 26  \w     39.00 106.00   0.50    0.22    --  109.61-101.00 -99.00  134
 27  \w     71.00 105.00   0.50    0.22    --  109.61 -99.00-150.00   68
 28  \w     40.00  66.00   0.50    0.22    --  109.61 -99.00-150.00   52
 29  \w     39.00  74.00   0.50    0.22    --  109.61 -99.00 -30.00   70
 30  \w     48.00  89.00   0.50    0.22    --  109.61 -99.00 -60.00   82
 31  \w     39.00 106.00   0.50    0.22    --  109.61 -99.00 150.00  134
 32  \w     77.00 104.00   0.50    0.22    --  109.61 -99.00  30.00   54
 33  \w     44.00  73.00   0.50    0.22    --  109.61 -99.00  30.00   58
 34  \w      4.00  81.00   0.50    0.05    --   47.33-101.00 -99.00  154
 35  \w     34.00  93.00   0.50    0.05    --   47.33-125.00-180.00  118
 36  \w     34.00  93.00   0.50    0.05    --   47.33-125.00   0.00  118
 37  \w   -119.00 -25.00   0.50    0.05    --  -47.33 -77.00 120.00  188
 38  \w   -119.00 -25.00   0.50    0.05    --  -47.33 -77.00 -60.00  188
 39  \w   -119.00 -25.00   0.50    0.05    --  -47.33 -77.00 -90.00  188
 40  \w   -119.00 -25.00   0.50    0.05    --  -47.33 -77.00-180.00  188
 41  \w   -162.00 -85.00   0.50    0.22    --  -91.75-101.00 -99.00  154
 42  \w    -92.00 -59.00   0.50    0.22    --  -82.00 -77.00-110.52   66
 43  \w   -126.00 -31.00   0.50    0.05    --  -54.00 -77.00 -99.09  190
 44  \w   -156.00-127.00   0.50    0.22    --  -91.75 -77.00-162.74   58
 45  \w   -110.00 -69.00   0.50    0.22    --  -91.75 -77.00-162.74   82
 46  \w    -89.00 -63.00   0.50    0.22    --  -86.00 -77.00 -55.63   52
 47  \w   -110.00 -69.00   0.50    0.22    --  -91.75 -77.00 -30.00   82
 48  \w   -151.00 -69.00   0.50    0.22    --  -91.75 -77.00 -65.36  164
 49  \w   -162.00-136.00   0.50    0.22    --  -91.75 -77.00 -30.00   52
 50  \w   -114.00 -69.00   0.50    0.22    --  -91.75 -77.00  90.00   90
 51  \w   -139.00 -43.00   0.50    0.05    --  -66.00 -77.00 176.54  192
 52  \w   -147.00-121.00   0.50    0.22    --  -91.75 -77.00  90.00   52
 53  \w   -161.00 -94.00   0.50    0.22    --  -91.75 -77.00  30.00  134
 54  \w    -77.00 -51.00   0.50    0.05    --  -74.00 -76.00  69.91   52
 55  \w    -77.00 -51.00   0.50    0.05    --  -74.00 -76.00 -20.06   52
 56  \w   -161.00 -69.00   0.50    0.22    --  -91.75 -77.00-180.00  184
 57  \w   -139.00 -43.00   0.50    0.05    --  -66.00 -76.00-123.20  192
 58  \w   -143.00 -47.00   0.50    0.05    --  -70.00 -77.00   0.34  192
 59  \w   -144.00 -67.00   0.50    0.22    --  -90.00 -76.00  61.89  154
 60  \w    -77.00 -51.00   0.50    0.05    --  -74.00 -76.00 145.45   52
 61  \w    -88.00 -63.00   0.50    0.22    --  -86.00 -76.00 136.35   50
 62  \w   -154.00-104.00   0.50    0.22    --  -86.00 -76.00 136.35  100
 63  \w    -98.00 -69.00   0.50    0.22    --  -91.75 -76.00  -0.79   58
 64  \w    -94.00 -69.00   0.50    0.22    --  -91.75 -76.00  15.30   50
 65  \w   -154.00-110.00   0.50    0.22    --  -91.75 -76.00  15.30   88
 66  \w   -163.00-128.00   0.50    0.22    --  -91.75 -76.00  -0.79   70
 67  \w    -78.00 -52.00   0.50    0.05    --  -74.00 -74.00 -79.53   52
 68  \w    -86.00 -60.00   0.50    0.22    --  -82.00 -75.00-130.18   52
 69  \w    -85.00 -52.00   0.50    0.05    --  -74.00 -75.00-150.35   66
 70  \w   -143.00 -70.00   0.50    0.22    --  -91.75 -75.00-147.78  146
 71  \w    -82.00 -56.00   0.50    0.05    --  -78.00 -74.00 106.21   52
 72  \w    -79.00 -53.00   0.50    0.05    --  -74.00 -74.00 130.10   52
 73  \w   -146.00 -70.00   0.50    0.22    --  -91.75 -74.00 160.43  152
 74  \w   -163.00-113.00   0.50    0.22    --  -91.75 -74.00 128.67  100
 75  \w   -101.00 -71.00   0.50    0.22    --  -91.75 -74.00 128.67   60
 76  \w   -100.00 -64.00   0.50    0.22    --  -86.00 -74.00  49.13   72
 77  \w   -148.00-108.00   0.50    0.22    --  -86.00 -74.00  49.13   80
 78  \w   -135.00 -40.00   0.50    0.05    --  -62.00 -74.00  32.89  190
 79  \w    -86.00 -60.00   0.50    0.22    --  -82.00 -74.00 -38.52   52
 80  \w    -88.00 -62.00   0.50    0.22    --  -82.00 -73.00 -94.99   52
 81  \w   -154.00-116.00   0.50    0.22    --  -82.00 -73.00 -94.99   76
 82  \w   -151.00-126.00   0.50    0.22    --  -91.75 -71.00-138.10   50
 83  \w   -161.00 -75.00   0.50    0.22    --  -91.75 -72.00 -82.38  172
 84  \w   -101.00 -71.00   0.50    0.22    --  -91.75 -71.00-138.10   60
 85  \w    -83.00 -54.00   0.50    0.05    --  -74.00 -71.00  15.93   58
 86  \w   -107.00 -71.00   0.50    0.22    --  -91.75 -71.00 102.54   72
 87  \w   -163.00-112.00   0.50    0.22    --  -91.75 -71.00 102.54  102
 88  \w   -139.00 -46.00   0.50    0.05    --  -66.00 -71.00  83.90  186
 89  \w   -101.00 -74.00   0.50    0.22    --  -91.75 -70.00-111.95   54
 90  \w   -163.00-111.00   0.50    0.22    --  -91.75 -70.00-111.95  104
 91  \w   -154.00 -89.00   0.50    0.22    --  -91.75 -57.00 -30.00  130
 92  \w    -41.00  26.00   0.50    0.05    --  -47.33  38.00-150.00  134
 93  \w    -81.00  18.00   0.50    0.05    --  -47.33 101.00   4.00  198
 94  \w    -84.00 -44.00   0.50    0.22    --  -91.75 125.00 -60.00   80
 95  \w    -78.00 -34.00   0.50    0.22    --  -91.75 101.00   4.00   88
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy, Dualflex, HyPix'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.1068175000
_diffrn_orient_matrix_UB_12      0.0841283000
_diffrn_orient_matrix_UB_13      0.0282759000
_diffrn_orient_matrix_UB_21      -0.0260247000
_diffrn_orient_matrix_UB_22      0.1099391000
_diffrn_orient_matrix_UB_23      -0.0300082000
_diffrn_orient_matrix_UB_31      -0.1701809000
_diffrn_orient_matrix_UB_32      -0.0695602000
_diffrn_orient_matrix_UB_33      -0.0131427000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.1116
_diffrn_reflns_av_unetI/netI     0.0270
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.987
_diffrn_reflns_limit_h_max       9
_diffrn_reflns_limit_h_min       -9
_diffrn_reflns_limit_k_max       12
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       43
_diffrn_reflns_limit_l_min       -44
_diffrn_reflns_number            93425
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 0.971
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         77.786
_diffrn_reflns_theta_min         2.482
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    4.312
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.42537
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.42.88a (Rigaku Oxford Diffraction, 2023)
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.477
_exptl_crystal_description       plate
_exptl_crystal_F_000             1237
_exptl_crystal_size_max          0.210
_exptl_crystal_size_mid          0.110
_exptl_crystal_size_min          0.080
_refine_diff_density_max         0.327
_refine_diff_density_min         -0.277
_refine_diff_density_rms         0.056
_refine_ls_abs_structure_details
;
 Flack x determined using 1917 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.046(7)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.146
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     366
_refine_ls_number_reflns         5579
_refine_ls_number_restraints     8
_refine_ls_restrained_S_all      1.151
_refine_ls_R_factor_all          0.0641
_refine_ls_R_factor_gt           0.0618
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0357P)^2^+3.1046P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1301
_refine_ls_wR_factor_ref         0.1312
_reflns_Friedel_coverage         0.714
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     0.949
_reflns_number_gt                5273
_reflns_number_total             5579
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d3ce00948c2.cif
_cod_data_source_block           TCA-LTAH
_cod_depositor_comments
'Adding full bibliography for 7247709--7247724.cif.'
_cod_database_code               7247719
_shelx_shelxl_version_number     2019/2
_shelx_estimated_absorpt_t_min   0.465
_shelx_estimated_absorpt_t_max   0.724
_oxdiff_exptl_absorpt_empirical_full_min 0.338
_oxdiff_exptl_absorpt_empirical_full_max 3.985
_oxdiff_exptl_absorpt_empirical_details
;
Empirical correction (ABSPACK) includes:
- Absorption correction using spherical harmonics
- Frame scaling
;
_shelx_res_checksum              25156