Synthesis, Characterization and structure-activity relationship of a novel pregabalin cocrystals with sustained-release performance
Ren, Jiaxuan; Wu, Di; Feng, Yaoguang; Zhang, Man; Yuan, Jiahui; Wang, Na; Wang, Ting; Huang, Xin; Hao, Hongxun; CrystEngComm  (2026) –; doi:10.1039/D6CE00023A

data_7251809
_publ_section_title
;
 Synthesis, characterization and structure--activity relationship of novel
 pregabalin cocrystals with sustained-release performance
;
_journal_issue                   17
_journal_name_full               CrystEngComm
_journal_page_first              2815
_journal_page_last               2834
_journal_paper_doi               10.1039/D6CE00023A
_journal_volume                  28
_journal_year                    2026
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C8 H17 N O2, C9 H8 O2'
_chemical_formula_sum            'C17 H25 N O4'
_chemical_formula_weight         307.38
_chemical_name_systematic        'Pregbalin-Cinnamic Acid Cocrystal'
_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   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2024-11-13
_audit_creation_method
;
Olex2 1.5
(compiled 2024.02.16 svn.r378c4104 for OlexSys, GUI svn.r6928)
;
_audit_update_record
;
2025-05-21 deposited with the CCDC.	2026-03-13 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   6.37480(10)
_cell_length_b                   7.71520(10)
_cell_length_c                   34.3678(3)
_cell_measurement_reflns_used    13464
_cell_measurement_temperature    100.00(10)
_cell_measurement_theta_max      75.8920
_cell_measurement_theta_min      5.1340
_cell_volume                     1690.31(4)
_computing_cell_refinement       'CrysAlisPro 1.171.43.136a (Rigaku OD, 2024)'
_computing_data_collection       'CrysAlisPro 1.171.43.136a (Rigaku OD, 2024)'
_computing_data_reduction        'CrysAlisPro 1.171.43.136a (Rigaku OD, 2024)'
_computing_molecular_graphics    'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT  (Sheldrick, 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100.00(10)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            'HyPix-Arc 150'
_diffrn_measured_fraction_theta_full 0.997
_diffrn_measured_fraction_theta_max 0.990
_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    -26.00   3.00   0.50    0.05    --  -54.63  45.00-150.00   58
  2  \w    -51.00 -26.00   0.50    0.05    --  -77.77  61.00-150.00   50
  3  \w    -54.00 -25.00   0.50    0.05    --  -77.77  61.00 -90.00   58
  4  \w    -32.00  -7.00   0.50    0.05    --  -63.67  45.00  30.00   50
  5  \w    -32.00  -7.00   0.50    0.05    --  -63.67  45.00 120.00   50
  6  \w    -32.00  -7.00   0.50    0.05    --  -63.67  45.00 150.00   50
  7  \w    -89.00 -34.00   0.50    0.05    --  -77.77 111.00 -30.00  110
  8  \w    -49.00 -18.00   0.50    0.05    --  -63.67  94.00 -68.00   62
  9  \w    -87.00 -53.00   0.50    0.05    --  -77.77  94.00 -68.00   68
 10  \w    -82.00 -57.00   0.50    0.05    --  -77.77 104.00-169.00   50
 11  \w    -47.00 -12.00   0.50    0.05    --  -63.67 104.00-169.00   70
 12  \w    -65.00 -40.00   0.50    0.05    --  -54.63 104.00-169.00   50
 13  \w   -108.00 -83.00   0.50    0.05    --  -54.63 -36.00 -61.00   50
 14  \w   -103.00 -78.00   0.50    0.05    --  -63.67 -36.00 -61.00   50
 15  \w   -131.00-106.00   0.50    0.05    --  -77.77 -36.00 -61.00   50
 16  \w     40.00  65.00   0.50    0.05    --   93.50-111.00-120.00   50
 17  \w     41.00  67.00   0.50    0.05    --   93.50-111.00-150.00   52
 18  \w     41.00  93.00   0.50    0.05    --   93.50-111.00   0.00  104
 19  \w      8.00  33.00   0.50    0.05    --   62.22-104.00  88.00   50
 20  \w     36.00  62.00   0.50    0.05    --   62.22-104.00  88.00   52
 21  \w     54.00  92.00   0.50    0.05    --   93.50-111.00 120.00   76
 22  \w     40.00  65.00   0.50    0.05    --   93.50-104.00  88.00   50
 23  \w     47.00  84.00   0.50    0.05    --   93.50 -94.00   0.00   74
 24  \w     58.00  83.00   0.50    0.05    --   93.50 -94.00  60.00   50
 25  \w     43.00  69.00   0.50    0.05    --   93.50 -94.00 -90.00   52
 26  \w     43.00  86.00   0.50    0.05    --   93.50 -94.00-120.00   86
 27  \w     43.00  68.00   0.50    0.05    --   93.50 -94.00-150.00   50
 28  \w     43.00  68.00   0.50    0.05    --   93.50 -94.00-179.00   50
 29  \w     10.00  35.00   0.50    0.05    --   53.96 -94.00-179.00   50
 30  \w    112.00 144.00   0.50    0.05    --   93.50  61.00 -60.00   64
 31  \w     95.00 143.00   0.50    0.05    --   93.50  61.00-120.00   96
 32  \w     97.00 136.00   0.50    0.05    --   93.50  45.00-180.00   78
 33  \w     96.00 145.00   0.50    0.05    --   93.50  36.00  94.00   98
 34  \w    100.00 149.00   0.50    0.05    --   93.50  45.00 150.00   98
 35  \w     68.00  93.00   0.50    0.05    --   62.22  36.00  94.00   50
 36  \w     73.00  98.00   0.50    0.05    --   53.96  36.00  94.00   50
 37  \w    111.00 137.00   0.50    0.05    --   93.50 111.00 150.00   52
 38  \w     97.00 147.00   0.50    0.05    --   93.50 111.00  60.00  100
 39  \w    118.00 143.00   0.50    0.05    --   93.50 111.00 -30.00   50
 40  \w    104.00 130.00   0.50    0.05    --   93.50 111.00 -90.00   52
 41  \w    119.00 144.00   0.50    0.05    --   93.50 111.00-120.00   50
 42  \w    123.00 148.00   0.50    0.05    --   93.50 104.00-169.00   50
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'ROD, Synergy Custom DW system, HyPix-Arc 150'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.1070867000
_diffrn_orient_matrix_UB_12      -0.1042705000
_diffrn_orient_matrix_UB_13      0.0326632000
_diffrn_orient_matrix_UB_21      -0.0307640000
_diffrn_orient_matrix_UB_22      -0.1533125000
_diffrn_orient_matrix_UB_23      -0.0281428000
_diffrn_orient_matrix_UB_31      0.2144230000
_diffrn_orient_matrix_UB_32      -0.0741057000
_diffrn_orient_matrix_UB_33      0.0122845000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0171
_diffrn_reflns_av_unetI/netI     0.0107
_diffrn_reflns_Laue_measured_fraction_full 0.997
_diffrn_reflns_Laue_measured_fraction_max 0.990
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -6
_diffrn_reflns_limit_k_max       9
_diffrn_reflns_limit_k_min       -9
_diffrn_reflns_limit_l_max       43
_diffrn_reflns_limit_l_min       -42
_diffrn_reflns_number            15609
_diffrn_reflns_point_group_measured_fraction_full 0.998
_diffrn_reflns_point_group_measured_fraction_max 0.988
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         76.110
_diffrn_reflns_theta_min         5.148
_diffrn_source                   'Rotating-anode X-ray tube'
_diffrn_source_type              'Rigaku (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.694
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.82172
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
'CrysAlisPro 1.171.43.136a (Rigaku Oxford Diffraction, 2024)'
_exptl_crystal_density_diffrn    1.208
_exptl_crystal_description       block
_exptl_crystal_F_000             664
_exptl_crystal_size_max          0.23
_exptl_crystal_size_mid          0.2
_exptl_crystal_size_min          0.17
_refine_diff_density_max         0.208
_refine_diff_density_min         -0.126
_refine_diff_density_rms         0.028
_refine_ls_abs_structure_details
;
 Flack x determined using 1401 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.05(3)
_refine_ls_extinction_coef       0.0078(7)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     'SHELXL-2018/3 (Sheldrick 2018)'
_refine_ls_goodness_of_fit_ref   1.042
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     204
_refine_ls_number_reflns         3484
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.042
_refine_ls_R_factor_all          0.0238
_refine_ls_R_factor_gt           0.0235
_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^)+(0.0349P)^2^+0.2740P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0623
_refine_ls_wR_factor_ref         0.0625
_reflns_Friedel_coverage         0.691
_reflns_Friedel_fraction_full    0.999
_reflns_Friedel_fraction_max     0.983
_reflns_number_gt                3442
_reflns_number_total             3484
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d6ce00023a2.cif
_cod_data_source_block           37-cr-20241112b_auto
_cod_depositor_comments
'Adding full bibliography for 7251808--7251810.cif.'
_cod_database_code               7251809
_shelx_shelxl_version_number     2018/3
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All N(H,H,H) groups, All O(H) groups
2.a Ternary CH refined with riding coordinates:
 C12(H12), C15(H15)
2.b Secondary CH2 refined with riding coordinates:
 C11(H11A,H11B), C13(H13A,H13B), C14(H14A,H14B)
2.c Aromatic/amide H refined with riding coordinates:
 C1(H1), C2(H2A), C3(H3), C4(H4), C5(H5), C7(H7), C8(H8)
2.d Idealised Me refined as rotating group:
 N1(H1A,H1B,H1C), C16(H16A,H16B,H16C), C17(H17A,H17B,H17C)
2.e Idealised tetrahedral OH refined as rotating group:
 O2(H2)
;
_shelx_res_checksum              91478
_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
;
_oxdiff_exptl_absorpt_empirical_full_max 1.266
_oxdiff_exptl_absorpt_empirical_full_min 0.606