The Identification and Characterization of a New Carbapenem CS-023 Solvate Polymorph Achieved by the Appropriate Crystal Washing and Drying

Figures & data

Figure 1. Chemical structure of CS-023.

Figure 2. The solvation of crystals washed and dried after the poor solvent crystallization in 70 v/v% ethanol. Washing with 70 v/v% ethanol. Drying: at 25–60 °C and 0.04 kPa, for 16–166 h.

Table 1. Crystallographic data on Form A and Form C^a.

Polymorphs	Form A	Form C
Solvate	5/2Ethanol·1/2H2O	1Ethanol·3H2O
Crystal system	triclinic	orthorhombic
Space group	P1	P212121
Unit cell dimensions
a [Å]	10.23	9.8570
b [Å]	13.21	13.1136
c [Å]	14.04	24.1859
α [°]	78.07	90
β[°]	89.02	90
γ [°]	76.63	90
Volume [Å^3]	1805.1	3113.2
Z	2	4
Density [Mg/m^3]	1.125	1.361
(calculated)

^a Form C was prepared by hanging drop crystallization.

Figure 3. Drying at 25 °C and 1.6 kPa. Washing with 75 v/v% ethanol. Reference: Intrinsic solvation of Form C: 10.04% H₂O, 8.55% EtOH.

Figure 4. Behavior of the washing solvent during the drying of crystals.

Figure 5. Raman spectroscopy measurement on Form C’s (001) surface exposed by a saturated CS-023 solution. A, B, C, D: Laser beam irradiation sites.

Figure 6. Raman spectroscopy data on Form C’s (001) surface exposed by a saturated CS-023 solution. A, B, C, D: Laser beam irradiation sites. (a) A comparison of Raman sift between Form C and Form H. (b) The changes in Raman spectroscopy with elapsed time.

Figure 7. Drying at 25 °C and 1.6 kPa. Washing with 96 v/v% ethanol. Reference: Intrinsic solvation of Form C: 10.04% H₂O, 8.55% EtOH.

Figure 8. An optical microphotograph of the CS-023 crystals recovered after 18 h-poor solvent crystallization under stirring.

Figure 9. The comparison of the XRD patterns between (a) the crystals recovered from 70 v/v% ethanol solution and (b) Form C estimated from the crystallographic information data.

Figure 10. The XRD data for the crystals formed in less than 70 v/v% ethanol and a comparison with Form A’s.

Figure 11. Water absorption and emission isotherms on Form C washed with 96 v/v% ethanol; Effect of crystal size.

Figure 12. Solubility of Form A and Form C at 25 °C in ethanol solution.

Figure 13. Changes in the concentration of CS-023 during the solvent mediated transformation of Form A to Form C at 25 °C. Solvent and the prepared Form A slurry: (a) 40 v/v% ethanol, 56 mg/mL, (b) 70 v/v% ethanol, 30 mg/mL, (c) 80 v/v% ethanol, 3 mg/mL. In all cases, Form C was recovered after (a) 60 min, (b) 60 min, (c) 30 h.