Combining API in a dual-drug ternary cocrystal approach

Area of Science:

• Materials Science
• Pharmaceutical Chemistry
• Crystallography

Background:

• Designing multi-drug solid forms presents challenges in achieving stable and effective formulations.
• Current methods often struggle to combine multiple active pharmaceutical ingredients (APIs) into a single, stable solid dosage form.

Purpose of the Study:

• To develop a new strategy for designing multi-drug solid forms using a "drug-bridge-drug" approach.
• To create and characterize novel ternary ionic cocrystals (TICCs) by linking two different APIs with an inorganic salt.
• To investigate the factors influencing TICC formation, stability, and solubility.

Main Methods:

• Synthesis and characterization of three different ternary ionic cocrystals (TICCs).
• Utilized ternary solid-state phase diagrams to understand the relationship between binary and ternary cocrystals and reaction stoichiometry.
• Evaluated the role of water in system stability and the impact on solubility compared to parent APIs.

Main Results:

• Successfully designed and synthesized three novel TICCs using the "drug-bridge-drug" strategy.
• Demonstrated the critical role of reaction stoichiometry and water in the stability and formation of these multi-drug systems.
• Observed significant improvements in solubility for the TICCs compared to their individual API components.

Conclusions:

• The developed "drug-bridge-drug" strategy provides a versatile and effective method for creating multi-drug solid forms.
• Ternary ionic cocrystals offer enhanced stability and solubility, representing a promising advancement in pharmaceutical formulation.
• This approach is expected to be broadly applicable to various drug combinations, paving the way for new multi-drug systems.