Amino Acids as the Potential Co-Former for Co-Crystal Development: A Review

Area of Science:

• Pharmaceutical Science
• Green Chemistry
• Materials Science

Background:

• Co-crystals modify active pharmaceutical ingredient (API) physicochemical properties via non-covalent interactions.
• Green chemistry principles drive the development of solvent-free or reduced-solvent co-crystallization methods.
• Identifying safer co-formers is crucial for eco-friendlier pharmaceutical processes.

Purpose of the Study:

• To review and highlight the advantages of using amino acids as safe co-formers in API modification.
• To explore the potential of amino acids in developing environmentally friendly co-crystallization techniques.
• To consolidate research on amino acid-based co-crystals and deep eutectic solvents for pharmaceutical applications.

Main Methods:

• Literature review of studies reporting the use of amino acids as co-formers.
• Analysis of the structural features of amino acids enabling hydrogen bonding and zwitterionic interactions.
• Examination of case studies demonstrating improved API properties using amino acid co-crystals and deep eutectic solvents.

Main Results:

• Amino acids possess functional groups ideal for hydrogen bonding and zwitterionic stabilization, enhancing API interactions.
• Amino acid-derived co-crystals and deep eutectic solvents have demonstrated improved pharmaceutical performance, including reduced side effects (e.g., l-glutamine with mesalamine).
• Specific amino acids like l-proline enhance API solubility and absorption, while others facilitate chiral resolution.

Conclusions:

• Amino acids are safe, effective co-formers for improving API physicochemical properties.
• Amino acid-based co-crystals and deep eutectic solvents offer promising avenues for advanced dosage form development.
• Further research into amino acids for solid-state synthesis and drug formulation is warranted.