Crystalline forms of carbapenem antibiotics and methods of preparation

A process for preparing a crystalline solvate carbapenem monosodium salt of formula IIa:

• comprising the steps of:
• a) adding an organic solvent selected from the group consisting of methanol and/or 1-propanol to an aqueous solution containing carbapenems of formula II and 4:
• and/or salt forms thereof,
• b) cooling the solution to below −5° C.;
• c) adjusting the pH to between about 6 and about 5 utilizing an acid;
• d) crystallizing by adding to the solution from about 0.5 to about 3.0 volumes of methanol relative to the aqueous solution volume, and optionally, from about 0.5 to about 3.0 volumes of [a C1-5 alcohol] 1-propanol relative to the aqueous solution volume, thereby producing a slurry of formula IIa carbapenem crystals;
• and
• e) [washing the formula IIa carbapenem crystals with methanol and 1-propanol and] isolating the formula IIa carbapenem crystals of Form A;
• and
• f) washing the formula IIa carbapenem crystals of Form A with water and 2-propanol and isolating the formula IIa carbapenem crystals of Form B.

A process for preparing a crystalline solvate carbapenem monosodium salt of general formula IIa, Form B:

• wherein Form B has an X-ray powder diffraction patter pattern 18.48, 13.02, 11.27, 8.50, 7.51, 6.51, 6.13, 5.82, 5.13, 4.78, 4.67, 4.50, 4.24, 4.06, 3.85, 3.69, 3.63, 3.41, 3.36, 3.31, 3.22, 3.11, 2.98, 2.87, and 2.77 angstroms;
• comprising:
• a) adding 1-propanol to an aqueous solution containing carbapenems of formula II and 4:
• and/or salt forms thereof,
• b) cooling the solution to below −5° C.;
• c) adjusting the pH to between about 6 and about 5 utilizing an acid;
• d) crystallizing by adding to the solution from about 0.5 to about 3.0 volumes of methanol relative to the aqueous volume, and from about 0.5 to a bout about 3.0 volumes of 1-propanol relative to the aqueous solution volume;
• and
• e) isolating the formula IIa Form A carbapenem crystals
• wherein Form A has an X-ray powder diffraction pattern 18.44, 13.09, 8.43, 7.58, 6.48, 6.16, 5.55, 5.14, 4.81, 4.50, 4.26, 4.11, 4.02, 3.85, 3.69, 3.41, 3,35, 3.35, 3.03, 3.25, 3.12 and 2.87 angstroms;
• and
• f) washing solids containing formula IIa Form A crystals with a mixture of water and 2-propanol to give the compound of formula IIa, Form B, wherein said mixture contains from about 5% to about 25% water (v/v).