Pharmaceutical solvates, hydrates and amorphous forms: A special emphasis on cocrystals

Area of Science:

• Pharmaceutical Science
• Solid-State Chemistry
• Drug Development

Background:

• Active pharmaceutical ingredients (APIs) can exist in multiple solid forms.
• These solid forms influence intermolecular interactions, internal energy, enthalpy, and entropy.
• Variations in solid forms affect critical physicochemical properties such as solubility, dissolution rate, stability, and mechanical characteristics.

Purpose of the Study:

• To review the fundamental characteristics and trends of pharmaceutical hydrates, solvates, and amorphous forms.
• To emphasize pharmaceutical hydrates, including single and two-component (cocrystal) host molecules, due to their prevalence.
• To highlight the importance of solid form selection in optimizing bioavailability, intellectual property protection, and manufacturing processes.

Main Methods:

• Literature review of fundamental characteristics and trends in pharmaceutical solid forms.
• Focus on pharmaceutical hydrates, including single-component and two-component (cocrystal) systems.
• Analysis of the impact of solid forms on thermodynamic parameters and physicochemical properties.

Main Results:

• Solid forms of APIs exhibit diverse characteristics affecting thermodynamic and physicochemical properties.
• Pharmaceutical hydrates, solvates, and amorphous forms present distinct properties.
• Hydrates, particularly those involving single and two-component host molecules, are abundant and significant.

Conclusions:

• Solid form characterization is vital for successful drug discovery and development.
• Understanding different solid forms, especially hydrates, aids in optimizing drug bioavailability and manufacturing.
• Selection of appropriate API solid forms is critical for intellectual property and process development.