Crystal engineering of the cystic fibrosis drug ivacaftor: salts, solvates and hydrate forms with solubility and stability studies
Doguparthi, Naga Prathyusha; Kanagavel, Manimurugan; Samreen, Sabiqa; Navya, Yaramala; Soujanya, Yarasi; Swain, Debasish; Nechipadappu, Sunil Kumar; CrystEngComm 28 (2026) 1621–1635; doi:10.1039/D5CE01068C

data_7251473
_publ_section_title
;
 Crystal engineering of the cystic fibrosis drug ivacaftor: salts,
 solvates and hydrate forms with solubility and stability studies
;
_journal_issue                   10
_journal_name_full               CrystEngComm
_journal_page_first              1621
_journal_page_last               1635
_journal_paper_doi               10.1039/D5CE01068C
_journal_volume                  28
_journal_year                    2026
_chemical_formula_moiety         'C24 H29 N2 O3, C2 H4 O2, Br'
_chemical_formula_sum            'C26 H33 Br N2 O5'
_chemical_formula_weight         533.45
_chemical_name_systematic        'ivacaftor hydrobromide acetic acid solvate'
_space_group_crystal_system      orthorhombic
_space_group_IT_number           33
_space_group_name_Hall           'P 2c -2n'
_space_group_name_H-M_alt        'P n a 21'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     difmap
_atom_sites_solution_secondary   difmap
_audit_creation_method           SHELXL-2019/3
_audit_update_record
;
2025-10-10 deposited with the CCDC.	2026-01-28 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   28.4445(15)
_cell_length_b                   9.0341(5)
_cell_length_c                   10.3513(4)
_cell_measurement_reflns_used    7364
_cell_measurement_temperature    294(2)
_cell_measurement_theta_max      24.18
_cell_measurement_theta_min      2.43
_cell_volume                     2660.0(2)
_computing_cell_refinement       '<i>SAINT</i> (Bruker, 2016)'
_computing_data_collection       '<i>APEX3</i> (Bruker, 2016)'
_computing_data_reduction        'Bruker SAINT'
_computing_molecular_graphics    'Bruker SHELXTL'
_computing_publication_material  'Bruker SHELXTL'
_computing_structure_refinement  'SHELXL-2018/3 (Sheldrick, 2018)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_temperature      294(2)
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.996
_diffrn_measurement_device_type  'Bruker D8 QUEST PHOTON-100'
_diffrn_measurement_method       '\w and \f'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0493
_diffrn_reflns_av_unetI/netI     0.0728
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.996
_diffrn_reflns_limit_h_max       37
_diffrn_reflns_limit_h_min       -37
_diffrn_reflns_limit_k_max       12
_diffrn_reflns_limit_k_min       -11
_diffrn_reflns_limit_l_max       10
_diffrn_reflns_limit_l_min       -13
_diffrn_reflns_number            22564
_diffrn_reflns_point_group_measured_fraction_full 0.898
_diffrn_reflns_point_group_measured_fraction_max 0.866
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         28.288
_diffrn_reflns_theta_min         2.365
_exptl_absorpt_coefficient_mu    1.582
_exptl_absorpt_correction_T_max  0.7457
_exptl_absorpt_correction_T_min  0.5684
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
 SADABS 2016/2: Krause, L., Herbst-Irmer, R., Sheldrick G.M. & Stalke D.,
 J. Appl. Cryst. 48 (2015) 3-10
;
_exptl_crystal_density_diffrn    1.332
_exptl_crystal_description       block
_exptl_crystal_F_000             1112
_exptl_crystal_recrystallization_method
'Re-crystallisation from solvent: acetic acid'
_exptl_crystal_size_max          0.200
_exptl_crystal_size_mid          0.160
_exptl_crystal_size_min          0.150
_refine_diff_density_max         0.490
_refine_diff_density_min         -0.706
_refine_diff_density_rms         0.065
_refine_ls_abs_structure_details
;
 Flack x determined using 1162 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.021(8)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.025
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     334
_refine_ls_number_reflns         5719
_refine_ls_number_restraints     6
_refine_ls_restrained_S_all      1.024
_refine_ls_R_factor_all          0.0945
_refine_ls_R_factor_gt           0.0422
_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^)+(0.0203P)^2^+1.2151P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0788
_refine_ls_wR_factor_ref         0.0962
_reflns_Friedel_coverage         0.649
_reflns_Friedel_fraction_full    0.784
_reflns_Friedel_fraction_max     0.720
_reflns_number_gt                3597
_reflns_number_total             5719
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5ce01068c2.cif
_cod_data_source_block           KB1747_0m
_cod_depositor_comments
'Adding full bibliography for 7251465--7251473.cif.'
_cod_database_code               7251473
_shelx_shelxl_version_number     2019/3
_shelx_estimated_absorpt_t_min   0.743
_shelx_estimated_absorpt_t_max   0.797
_shelx_res_checksum              19568