Formulation of a danazol cocrystal with controlled supersaturation plays an essential role in improving bioavailability.
Childs, Scott L.; Kandi, Praveen; Lingireddy, Sreenivas Reddy; Molecular pharmaceutics 10 (2013) 3112–3127; doi:10.1021/mp400176y

data_1512142
_publ_section_title
;
 Formulation of a danazol cocrystal with controlled supersaturation plays
 an essential role in improving bioavailability.
;
_journal_issue                   8
_journal_name_full               'Molecular pharmaceutics'
_journal_page_first              3112
_journal_page_last               3127
_journal_paper_doi               10.1021/mp400176y
_journal_volume                  10
_journal_year                    2013
_chemical_absolute_configuration unk
_chemical_formula_moiety         'C22 H27 N O2, C8 H8 O3'
_chemical_formula_sum            'C30 H35 N O5'
_chemical_formula_weight         489.59
_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'
_symmetry_space_group_name_Hall  'P 2ac 2ab'
_symmetry_space_group_name_H-M   'P 21 21 21'
_atom_sites_solution_hydrogens   difmap
_atom_sites_solution_primary     iterative
_audit_creation_date             2012-11-27
_audit_creation_method
;
  Olex2 1.2-beta
  (compiled Nov  5 2012 18:25:38, GUI svn.r4372)
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   6.6170(3)
_cell_length_b                   19.6403(10)
_cell_length_c                   20.1853(9)
_cell_measurement_reflns_used    9785
_cell_measurement_temperature    173(2)
_cell_measurement_theta_max      69.695
_cell_measurement_theta_min      3.140
_cell_volume                     2623.3(2)
_computing_cell_refinement       'SAINT v7.68A (Bruker, 2009)'
_computing_data_collection       'APEX2 v2011.2-4 (Bruker, 2011)'
_computing_data_reduction        'SAINT v7.68A (Bruker, 2009)'
_computing_molecular_graphics
;
O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard and H. Puschmann,
OLEX2: a complete structure solution, refinement and analysis program.
J. Appl. Cryst. (2009). 42, 339-341.
;
_computing_publication_material
;
O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard and H. Puschmann,
OLEX2: a complete structure solution, refinement and analysis program.
J. Appl. Cryst. (2009). 42, 339-341.
;
_computing_structure_refinement  'SHELXL-97 (Sheldrick, 2008)'
_computing_structure_solution    'SHELXS-97 (Sheldrick, 2008)'
_diffrn_ambient_temperature      173(2)
_diffrn_detector_area_resol_mean 512
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.993
_diffrn_measurement_device_type  'Bruker D8 diffractometer with APEX2 detector'
_diffrn_measurement_method       '\f and \w scans with a narrow frame width'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0384
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.993
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       16
_diffrn_reflns_limit_k_min       -23
_diffrn_reflns_limit_l_max       24
_diffrn_reflns_limit_l_min       -23
_diffrn_reflns_number            14181
_diffrn_reflns_point_group_measured_fraction_full 0.970
_diffrn_reflns_point_group_measured_fraction_max 0.958
_diffrn_reflns_theta_full        67.679
_diffrn_reflns_theta_max         69.611
_diffrn_reflns_theta_min         3.139
_diffrn_source                   'sealed tube'
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.673
_exptl_absorpt_correction_T_max  0.7532
_exptl_absorpt_correction_T_min  0.4598
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2012/1 (Bruker,2012) was used for absorption correction.
wR2(int) was 0.1189 before and 0.0612 after correction.
The Ratio of minimum to maximum transmission is 0.6105.
The \l/2 correction factor is 0.0015.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.240
_exptl_crystal_F_000             1048
_exptl_crystal_size_max          0.5
_exptl_crystal_size_mid          0.292
_exptl_crystal_size_min          0.044
_refine_diff_density_max         0.193
_refine_diff_density_min         -0.212
_refine_diff_density_rms         0.039
_refine_ls_abs_structure_details
;
 Flack x determined using 1736 quotients [(I+)-I(-)]/[(I+)+(I-)]
 (Parsons and Flack (2004), Acta Cryst. A60, s61).
;
_refine_ls_abs_structure_Flack   0.10(11)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.045
_refine_ls_hydrogen_treatment    refall
_refine_ls_matrix_type           full
_refine_ls_number_parameters     450
_refine_ls_number_reflns         4709
_refine_ls_number_restraints     21
_refine_ls_restrained_S_all      1.043
_refine_ls_R_factor_all          0.0409
_refine_ls_R_factor_gt           0.0384
_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^)+(0.0681P)^2^]
 where P=(Fo^2^+2Fc^2^)/3
;
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0996
_refine_ls_wR_factor_ref         0.1016
_reflns_Friedel_coverage         0.679
_reflns_Friedel_fraction_full    0.931
_reflns_Friedel_fraction_max     0.911
_reflns_number_gt                4427
_reflns_number_total             4709
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            mp400176y_si_001.cif
_cod_data_source_block           a112g246
_cod_database_code               1512142
_diffrn_reflns_sigmai/neti       0.0397
_olex2_refinement_description
;
1. Restrained distances
 O2-H2
 0.99 with sigma of 0.01
 C16-H16
 0.95 with sigma of 0.01
 C1-H1
 0.99 with sigma of 0.01
 C19-H19C ~ C19-H19B ~ C19-H19A ~ C22-H22C ~ C22-H22A ~ C22-H22B
 with sigma of 0.005
 C25-H25B ~ C25-H25C ~ C25-H25A
 with sigma of 0.005
2. Uiso/Uaniso restraints and constraints
Uiso(H17B) = Uiso(H17A) = Uiso(H18B) = Uiso(H18A) = Uiso(H13A) = Uiso(H13B) = Uiso(H14A) = Uiso(H14B) = Uiso(H7A) = Uiso(H7B)
Uiso(H19A) = Uiso(H19C) = Uiso(H19B)
Uiso(H22A) = Uiso(H22B) = Uiso(H22C)
Uiso(H25A) = Uiso(H25B) = Uiso(H25C)
;
_shelx_estimated_absorpt_t_max   0.971
_shelx_estimated_absorpt_t_min   0.553
_shelx_hkl_checksum              6870
_shelx_res_checksum              88974
_shelxl_version_number           2012-4