Studies on the Vitrified and Cryomilled Bosentan

Area of Science:

• Materials Science
• Physical Chemistry
• Pharmaceutical Sciences

Background:

• Amorphous forms of drugs can exhibit improved solubility and dissolution rates compared to crystalline forms.
• Understanding the physical stability and molecular dynamics of amorphous drugs is crucial for formulation development.
• Vitrification and cryomilling are two common methods for producing amorphous solid dispersions.

Purpose of the Study:

• To characterize and compare the structural, thermal, and dynamic properties of amorphous bosentan (BOS) prepared by vitrification and cryomilling.
• To investigate the impact of preparation method on the physical stability and dissolution rate of amorphous BOS.
• To elucidate the role of water content in amorphous BOS prepared by cryomilling.

Main Methods:

• X-ray diffraction (XRD)
• Differential scanning calorimetry (DSC)
• Thermogravimetry (TGA)
• Fourier transform infrared spectroscopy (FTIR)
• Broad-band dielectric spectroscopy (BDS)

Main Results:

• Both vitrified and cryomilled BOS showed similar structural and H-bonding characteristics.
• Cryomilled BOS exhibited slower alpha-relaxation dynamics and higher physical stability (aging) compared to vitrified BOS.
• Cryomilled BOS demonstrated a lower intrinsic dissolution rate in the initial stages compared to vitrified BOS.
• Cryomilling of BOS monohydrate resulted in a nearly anhydrous amorphous form, contrasting with trehalose.

Conclusions:

• Cryomilling enhances the physical stability of amorphous BOS but reduces its initial dissolution rate.
• The preparation method significantly influences the properties and performance of amorphous drugs.
• Cryomilling offers a potential route for producing anhydrous amorphous forms of certain drugs.