Amorphous Drug-Polymer Salt with High Stability under Tropical Conditions and Fast Dissolution: The Case of Clofazimine and Poly(acrylic acid).
Gui, Yue; McCann, Erin C.; Yao, Xin; Li, Yuhui; Jones, Karen J.; Yu, Lian; Molecular pharmaceutics 18 (2021) 1364–1372; doi:10.1021/acs.molpharmaceut.0c01180

data_1560811
_publ_section_title
;
 Amorphous Drug-Polymer Salt with High Stability under Tropical Conditions
 and Fast Dissolution: The Case of Clofazimine and Poly(acrylic acid).
;
_journal_issue                   3
_journal_name_full               'Molecular pharmaceutics'
_journal_page_first              1364
_journal_page_last               1372
_journal_paper_doi               10.1021/acs.molpharmaceut.0c01180
_journal_volume                  18
_journal_year                    2021
_chemical_formula_moiety         'C27 H23 Cl2 N4, C12 H25 O4 S'
_chemical_formula_sum            'C39 H48 Cl2 N4 O4 S'
_chemical_formula_weight         739.77
_space_group_crystal_system      triclinic
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2020-09-18
_audit_creation_method
;
Olex2 1.3
(compiled 2020.07.31 svn.rc2a77460 for OlexSys, GUI svn.r6145)
;
_cell_angle_alpha                116.386(10)
_cell_angle_beta                 91.271(8)
_cell_angle_gamma                108.043(6)
_cell_formula_units_Z            2
_cell_length_a                   10.9239(13)
_cell_length_b                   13.7852(15)
_cell_length_c                   14.6224(16)
_cell_measurement_reflns_used    5661
_cell_measurement_temperature    100.0
_cell_measurement_theta_max      78.913
_cell_measurement_theta_min      3.435
_cell_volume                     1842.2(4)
_computing_cell_refinement       'APEX3 (Bruker AXS Inc., 2019)'
_computing_data_collection
;
Bruker Instrument Service, BIS, v.6.2.12 (Bruker AXS Inc., 2019)'
;
_computing_data_reduction        'SAINT V8.40A (Bruker AXS Inc., 2019)'
_computing_molecular_graphics    'OLEX2 (Dolomanov et al., 2009)'
_computing_publication_material  'OLEX2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2018/3 (Sheldrick, 2015b)'
_computing_structure_solution    'SHELXT, VERSION 2014/5 (Sheldrick, 2015a)'
_diffrn_ambient_temperature      100.0
_diffrn_detector                 '100 \\times 140 mm^2^ CMOS sensor'
_diffrn_detector_area_resol_mean 7.41
_diffrn_detector_type            'Bruker PHOTON III'
_diffrn_measured_fraction_theta_full 0.997
_diffrn_measured_fraction_theta_max 0.956
_diffrn_measurement_device       '\k-geometry four-circle diffractometer'
_diffrn_measurement_device_type  'Bruker D8 VENTURE'
_diffrn_measurement_method       '0.5\ \w and 0.5\ \f scans'
_diffrn_radiation_collimation    'focusing mirror'
_diffrn_radiation_detector       'Bruker PHOTON III'
_diffrn_radiation_monochromator  'multilayer mirror'
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54178
_diffrn_radiation_xray_symbol    K-L~3~
_diffrn_reflns_av_R_equivalents  0.0806
_diffrn_reflns_av_unetI/netI     0.0835
_diffrn_reflns_Laue_measured_fraction_full 0.997
_diffrn_reflns_Laue_measured_fraction_max 0.956
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -13
_diffrn_reflns_limit_k_max       17
_diffrn_reflns_limit_k_min       -17
_diffrn_reflns_limit_l_max       18
_diffrn_reflns_limit_l_min       -18
_diffrn_reflns_number            19377
_diffrn_reflns_point_group_measured_fraction_full 0.997
_diffrn_reflns_point_group_measured_fraction_max 0.956
_diffrn_reflns_theta_full        67.000
_diffrn_reflns_theta_max         79.363
_diffrn_reflns_theta_min         3.435
_diffrn_source                   'microfocus sealed X-ray tube'
_diffrn_source_current           1.1
_diffrn_source_power             0.055
_diffrn_source_type              'Incoatec I\mS 3.0'
_diffrn_source_voltage           50.0
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    2.486
_exptl_absorpt_correction_T_max  0.7746
_exptl_absorpt_correction_T_min  0.6260
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
'SADABS-2016/2 (Krause et al., 2015) was used for absorption correction.'
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.334
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       blade
_exptl_crystal_F_000             784
_exptl_crystal_size_max          0.14
_exptl_crystal_size_mid          0.07
_exptl_crystal_size_min          0.01
_refine_diff_density_max         0.474
_refine_diff_density_min         -0.422
_refine_diff_density_rms         0.069
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.032
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     471
_refine_ls_number_reflns         7647
_refine_ls_number_restraints     6
_refine_ls_restrained_S_all      1.040
_refine_ls_R_factor_all          0.0815
_refine_ls_R_factor_gt           0.0530
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0569P)^2^+0.2315P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1208
_refine_ls_wR_factor_ref         0.1347
_reflns_Friedel_coverage         0.000
_reflns_number_gt                5420
_reflns_number_total             7647
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            mp0c01180_si_002.cif
_cod_data_source_block           yu216
_cod_database_code               1560811
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.976
_shelx_estimated_absorpt_t_min   0.722
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All C(H,H,H,H) groups, All N(H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2. Uiso/Uaniso restraints and constraints
Uiso(C37A) = Uiso(C38A) = Uiso(C39A)
3. Same fragment restrains
{C35, C36, C37A, C38A, C39A} sigma for 1-2: 0.008, 1-3: 0.016
as in
{C35, C36, C37, C38, C39}
4. Others
 Sof(H36C)=Sof(H36D)=Sof(C37A)=Sof(H37C)=Sof(H37D)=Sof(C38A)=Sof(H38C)=
 Sof(H38D)=Sof(C39A)=Sof(H39D)=Sof(H39E)=Sof(H39F)=1-FVAR(1)
 Sof(H36A)=Sof(H36B)=Sof(C37)=Sof(H37A)=Sof(H37B)=Sof(C38)=Sof(H38A)=Sof(H38B)=
 Sof(C39)=Sof(H39A)=Sof(H39B)=Sof(H39C)=FVAR(1)
 Fixed Uiso: C37A(0.048) C38A(0.048) C39A(0.048)
5.a Ternary CH refined with riding coordinates:
 C25(H25)
5.b Secondary CH2 refined with riding coordinates:
 C28(H28A,H28B), C29(H29A,H29B), C30(H30A,H30B), C31(H31A,H31B), C32(H32A,
 H32B), C33(H33A,H33B), C34(H34A,H34B), C35(H35A,H35B), C36(H36A,H36B),
 C36(H36C,H36D), C37(H37A,H37B), C38(H38A,H38B), C37A(H37C,H37D), C38A(H38C,
 H38D)
5.c Aromatic/amide H refined with riding coordinates:
 C2(H2), C3(H3), C5(H5), C6(H6), C8(H8), C11(H11), C12(H12), C13(H13),
 C14(H14), C17(H17), C18(H18), C20(H20), C21(H21), C23(H23)
5.d Idealised Me refined as rotating group:
 C26(H26A,H26B,H26C), C27(H27A,H27B,H27C), C39(H39A,H39B,H39C), C39A(H39D,H39E,
 H39F)
;
_shelx_res_checksum              43515
_shelx_hkl_checksum              86273
_olex2_submission_special_instructions 'No special instructions were received'