Stabilizing Unstable Amorphous Menthol through Inclusion in Mesoporous Silica Hosts

Area of Science:

• Materials Science
• Physical Chemistry
• Pharmaceutical Sciences

Background:

• Menthol, a crystallizable therapeutic and food additive, often requires stabilization for effective drug delivery.
• Mesoporous silica matrices offer a promising platform for stabilizing amorphous forms of active pharmaceutical ingredients.

Purpose of the Study:

• To investigate the amorphization of neat menthol within mesoporous silica matrices of varying pore sizes (3.2 and 5.9 nm).
• To characterize the physical state and molecular mobility of menthol within these matrices.
• To evaluate the potential of these composites as drug delivery systems with tunable release profiles.

Main Methods:

• Loading neat menthol into mesoporous silica with 3.2 nm and 5.9 nm pores.
• Differential Scanning Calorimetry (DSC) to detect glass transitions and confirm amorphization.
• Dielectric Relaxation Spectroscopy (DRS) to probe menthol molecular mobility and identify relaxation processes (α and S-processes).

Main Results:

• Successful amorphization of menthol was achieved in both pore sizes, evidenced by calorimetric glass transitions (T_g = -54.3 °C).
• Nonisothermal crystallization was suppressed, indicating a stable amorphous/supercooled state within the silica pores.
• DRS revealed two relaxation processes: a faster α-process (neat-like menthol) and a slower, dominant S-process (adsorbed menthol).
• The 5.9 nm pore size showed a greater fraction of mobile α-process molecules, leading to faster initial drug release.
• The 3.2 nm pore size inhibited crystallization due to pore dimensions smaller than menthol's critical nucleation size.

Conclusions:

• Mesoporous silica matrices effectively stabilize amorphous menthol, preventing crystallization.
• Tuning the host pore size allows control over menthol mobility and consequently, drug release kinetics.
• These menthol-silica composites show significant potential as tunable drug delivery systems.