Freeze crystallization of imipenem

Area of Science:

• Pharmaceutical Sciences
• Chemical Engineering
• Materials Science

Background:

• Imipenem, a vital antibiotic, requires a stable crystalline form for improved solubility and efficacy.
• Traditional crystallization methods may not yield optimal physical properties for imipenem.
• Freeze crystallization offers a potential route for producing desirable crystalline forms.

Purpose of the Study:

• To investigate the relationship between freeze crystallization process parameters and imipenem product crystallinity.
• To understand the role of the liquid phase in the phase transition of amorphous imipenem to crystalline forms.
• To optimize freeze crystallization for producing a rapidly soluble and stable crystalline imipenem.

Main Methods:

• Freeze crystallization of imipenem and sodium bicarbonate in acetone-water solvent systems.
• Systematic variation of solvent ratios and crystallization temperatures.
• X-ray powder diffraction (XRPD) for quantifying the degree of product crystallinity.
• Utilizing the acetone-water solid-liquid (S-L) phase diagram for correlation analysis.

Main Results:

• The degree of imipenem crystallinity was directly correlated with the percentage of equilibrium liquid during freeze crystallization.
• Imipenem exhibited very low solubility in the identified equilibrium liquid phases.
• The phase transition from amorphous to crystalline imipenem is facilitated by the presence of the liquid phase.

Conclusions:

• Freeze crystallization conditions significantly influence the crystallinity of imipenem.
• The liquid phase plays a critical mediating role in the amorphous-to-crystalline phase transition of imipenem.
• Optimized freeze crystallization can yield a highly soluble and stable crystalline form of imipenem.