The preparation, characterization, structure and dissolution analysis of apremilast solvatomorphs

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry
• Drug Development

Background:

• Apremilast (AP) is a phosphodiesterase-4 (PDE4) inhibitor used to treat active psoriatic arthritis.
• Understanding drug solvate formation is crucial for optimizing pharmaceutical formulations and bioavailability.
• Previous research has not extensively detailed the solvatomorphs of Apremilast.

Purpose of the Study:

• To investigate the ability of Apremilast (AP) to form solvates.
• To characterize novel AP solvatomorphs and analyze their solid-state properties.
• To compare the in vitro dissolution profiles of AP solvatomorphs with commercial Apremilast tablets.

Main Methods:

• Synthesis and isolation of three Apremilast solvatomorphs: ethyl acetate hemisolvate, toluene hemisolvate, and dichloromethane monosolvate.
• Characterization using X-ray powder diffraction (XRPD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC).
• Single-crystal X-ray diffraction for detailed structural analysis, including crystal symmetry, packing, stoichiometry, and hydrogen bonding.
• In vitro dissolution testing of solvatomorph tablets compared to commercial Apremilast tablets.

Main Results:

• Three novel Apremilast solvatomorphs were successfully obtained and characterized.
• Structural analysis revealed distinct crystal packing, stoichiometry, and hydrogen-bonding patterns for each solvatomorph.
• All three solvatomorphs demonstrated comparable in vitro dissolution rates to commercial Apremilast tablets, indicated by similar f2 values.

Conclusions:

• Apremilast can form stable solvates with ethyl acetate, toluene, and dichloromethane.
• The characterized solvatomorphs possess unique solid-state properties but maintain similar dissolution behavior.
• These findings contribute to the understanding of Apremilast's solid-state chemistry and may inform future formulation development.