Cocrystallization of lenvatinib and temozolomide to improve the performance in terms of stability, dissolution, and tabletability
Wang, Zhi-Qing; Dai, Xia-Lin; Gu, Dai-Lin; Wu, Chao; Lu, Tong-Bu; Long, Xiang-Tian; Chen, Jia-Mei; CrystEngComm 25 (2023) 4189–4198; doi:10.1039/D3CE00473B

data_7246889
_publ_section_title
;
 Cocrystallization of lenvatinib and temozolomide to improve the
 performance in terms of stability, dissolution, and tabletability
;
_journal_issue                   29
_journal_name_full               CrystEngComm
_journal_page_first              4189
_journal_page_last               4198
_journal_paper_doi               10.1039/D3CE00473B
_journal_volume                  25
_journal_year                    2023
_chemical_formula_moiety         'C21 H19 Cl N4 O4, C6 H6 N6 O2, C H4 O'
_chemical_formula_sum            'C28 H29 Cl N10 O7'
_chemical_formula_weight         653.06
_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   geom
_audit_creation_date             2023-06-18
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2023-06-18 deposited with the CCDC.	2023-06-20 downloaded from the CCDC.
;
_cell_angle_alpha                68.871(3)
_cell_angle_beta                 78.281(3)
_cell_angle_gamma                79.368(3)
_cell_formula_units_Z            2
_cell_length_a                   7.1842(3)
_cell_length_b                   14.4765(5)
_cell_length_c                   15.9555(4)
_cell_measurement_reflns_used    6838
_cell_measurement_temperature    297.24(10)
_cell_measurement_theta_max      78.5070
_cell_measurement_theta_min      2.9780
_cell_volume                     1504.29(10)
_computing_cell_refinement       'CrysAlisPro 1.171.39.46e (Rigaku OD, 2018)'
_computing_data_collection       'CrysAlisPro 1.171.39.46e (Rigaku OD, 2018)'
_computing_data_reduction        'CrysAlisPro 1.171.39.46e (Rigaku OD, 2018)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2014/5 (Sheldrick, 2014)'
_diffrn_ambient_temperature      297.24(10)
_diffrn_measured_fraction_theta_full 0.970
_diffrn_measured_fraction_theta_max 0.970
_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    -89.00 -10.00   0.50    0.50    --    0.00 -36.00 -90.17  158
  2  \w    -89.00 -60.00   0.50    0.50    --    0.00 -57.00 -30.00   58
  3  \w    -25.00   0.00   0.50    0.50    --    0.00  57.00 -90.00   50
  4  \w    -87.00 -31.00   0.50    0.50    --    0.00 -57.00  30.00  112
  5  \w    -52.00  28.00   0.50    0.50    --    0.00 -57.00 -30.00  160
  6  \w      5.00  66.00   0.50    0.50    --    0.00  57.00 -90.00  122
  7  \w    110.00 135.00   0.50    5.00    --  106.20 -45.00 150.00   50
  8  \w     73.00  99.00   0.50    5.00    --  106.20 -45.00 150.00   52
  9  \w    144.00 170.00   0.50    5.00    --  106.20  15.00  90.00   52
 10  \w     20.00  97.00   0.50    5.00    --  106.20 -82.00-120.00  154
 11  \w     19.00 142.00   0.50    5.00    --  106.20 -82.00  90.00  246
 12  \w     17.00  98.00   0.50    5.00    --  106.20 -30.00  90.00  162
 13  \w    103.00 134.00   0.50    5.00    --  106.20 -30.00  90.00   62
 14  \w     19.00 110.00   0.50    5.00    --  106.20 -61.00 -90.00  182
 15  \w     23.00  49.00   0.50    5.00    --  106.20 -45.00 150.00   52
 16  \w    123.00 196.00   0.50    5.00    --  106.20  30.00 -60.00  146
 17  \w     73.00 112.00   0.50    5.00    --  106.20  30.00 -60.00   78
 18  \w     90.00 135.00   0.50    5.00    --  106.20 -82.00   0.00   90
 19  \w     51.00 142.00   0.50    5.00    --  106.20 -82.00 -90.00  182
 20  \w     92.00 117.00   0.50    5.00    --  106.20  61.00 -60.00   50
 21  \w     58.00 117.00   0.50    5.00    --  106.20 -82.00 150.00  118
 22  \w     18.00  74.00   0.50    5.00    --  106.20 -30.00  60.00  112
 23  \w    111.00 140.00   0.50    5.00    --  106.20 -30.00  60.00   58
 24  \w     49.00  90.00   0.50    5.00    --  106.20 -82.00  30.00   82
 25  \w    103.00 129.00   0.50    5.00    --  106.20 -82.00  30.00   52
 26  \w     30.00 138.00   0.50    5.00    --  106.20 -30.00 -60.00  216
 27  \w     76.00 101.00   0.50    5.00    --  106.20 -77.00-180.00   50
 28  \w     76.00 106.00   0.50    5.00    --  106.20 -82.00  60.00   60
 29  \w     19.00 133.00   0.50    5.00    --  106.20  15.00  90.00  228
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB AFC12 (RINC): Kappa dual home/near'
_diffrn_measurement_method       '\w scans'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0570
_diffrn_reflns_av_unetI/netI     0.0659
_diffrn_reflns_Laue_measured_fraction_full 0.970
_diffrn_reflns_Laue_measured_fraction_max 0.970
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       16
_diffrn_reflns_limit_k_min       -16
_diffrn_reflns_limit_l_max       13
_diffrn_reflns_limit_l_min       -18
_diffrn_reflns_number            12610
_diffrn_reflns_point_group_measured_fraction_full 0.970
_diffrn_reflns_point_group_measured_fraction_max 0.970
_diffrn_reflns_theta_full        63.999
_diffrn_reflns_theta_max         63.999
_diffrn_reflns_theta_min         3.003
_exptl_absorpt_coefficient_mu    1.680
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.52843
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.39.46e (Rigaku Oxford Diffraction, 2018)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.442
_exptl_crystal_description       block
_exptl_crystal_F_000             680
_exptl_crystal_size_max          0.15
_exptl_crystal_size_mid          0.08
_exptl_crystal_size_min          0.04
_refine_diff_density_max         0.256
_refine_diff_density_min         -0.325
_refine_diff_density_rms         0.055
_refine_ls_extinction_coef       0.0019(4)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     'SHELXL-2016/6 (Sheldrick 2016)'
_refine_ls_goodness_of_fit_ref   1.099
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     439
_refine_ls_number_reflns         4849
_refine_ls_number_restraints     96
_refine_ls_restrained_S_all      1.101
_refine_ls_R_factor_all          0.0707
_refine_ls_R_factor_gt           0.0500
_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^)+(0.0886P)^2^+0.0253P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1317
_refine_ls_wR_factor_ref         0.1482
_reflns_Friedel_coverage         0.000
_reflns_number_gt                3764
_reflns_number_total             4849
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d3ce00473b2.cif
_cod_data_source_block           211006-tmz-len
_cod_depositor_comments          'Adding full bibliography for 7246889.cif.'
_cod_database_code               7246889
_shelx_shelxl_version_number     2016/6
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H) groups, All N(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups
2. Restrained distances
 C3-C1B \\sim C3-C1A
 with sigma of 0.04
 C1B-C2B \\sim C1A-C2A
 with sigma of 0.02
 C3-C2B \\sim C3-C2A
 with sigma of 0.04
 C2B-C3 \\sim C3-C2A
 with sigma of 0.01
 C1B-C3 \\sim C3-C1A
 with sigma of 0.01
 C2A-C1A \\sim C1B-C2B
 with sigma of 0.01
3. Rigid bond restraints
 C3, C1B, C2B
 with sigma for 1-2 distances of 0.005 and sigma for 1-3 distances of 0.01
 C3, C2A, C1A
 with sigma for 1-2 distances of 0.005 and sigma for 1-3 distances of 0.01
4. Uiso/Uaniso restraints and constraints
C3 \\sim C1B \\sim C2B: within 2A with sigma of 0.01 and sigma for terminal
atoms of 0.02
C3 \\sim C2A \\sim C1A: within 2A with sigma of 0.01 and sigma for terminal
atoms of 0.02
Uanis(C3) \\sim Ueq, Uanis(C1B) \\sim Ueq, Uanis(C2B) \\sim Ueq: with sigma of
0.04 and sigma for terminal atoms of 0.06
Uanis(C3) \\sim Ueq, Uanis(C2A) \\sim Ueq, Uanis(C1A) \\sim Ueq: with sigma of
0.04 and sigma for terminal atoms of 0.06
5. Rigid body (RIGU) restrains
 C3, C1B, C2B
 with sigma for 1-2 distances of 0.0005 and sigma for 1-3 distances of 0.0005
 C3, C2A, C1A
 with sigma for 1-2 distances of 0.0005 and sigma for 1-3 distances of 0.0005
6. Others
 Sof(H3B)=Sof(C2A)=Sof(H2AA)=Sof(H2AB)=Sof(C1A)=Sof(H1AA)=Sof(H1AB)=1-FVAR(1)
 Sof(H3A)=Sof(C1B)=Sof(H1BA)=Sof(H1BB)=Sof(C2B)=Sof(H2BA)=Sof(H2BB)=FVAR(1)
7.a Ternary CH refined with riding coordinates:
 C3(H3A), C3(H3B)
7.b Secondary CH2 refined with riding coordinates:
 C1B(H1BA,H1BB), C2B(H2BA,H2BB), C2A(H2AA,H2AB), C1A(H1AA,H1AB)
7.c Aromatic/amide H refined with riding coordinates:
 N2(H2), N1(H1), C17(H17), C16(H16), C9(H9), C25(H25), C11(H11), C12(H12),
 C6(H6), C8(H8)
7.d X=CH2 refined with riding coordinates:
 N5(H5A,H5B), N4(H4A,H4B)
7.e Idealised Me refined as rotating group:
 C27(H27A,H27B,H27C), C21(H21A,H21B,H21C), C28(H28A,H28B,H28C)
7.f Idealised tetrahedral OH refined as rotating group:
 O7(H7)
;
_shelx_res_checksum              68154
_olex2_submission_special_instructions 'No special instructions were received'
_oxdiff_exptl_absorpt_empirical_details
;
Empirical correction (ABSPACK) includes:
- Absorption correction using spherical harmonics
- Frame scaling
;