Amorphous stabilization of BCS II drugs using mesoporous silica

This study aimed to investigate the amorphous stabilization of BCS Class II drugs using mesoporous silica as a carrier to produce amorphous solid dispersions. Ibuprofen, fenofibrate, and budesonide were selected as model drugs to evaluate the impact of molecular weight and partition coefficient on the solid state of drug-loaded mesoporous silica (MS) particles. The model drugs were loaded into three grades of MS, SYLYSIA SY730, SYLYSIA SY430, and SYLYSIA SY350, with pore diameters of 2.5 nm, 17 nm, and 21 nm, respectively, at 1:1, 2:1, and 3:1, carrier to drug ratios, and three different loading concentrations using solvent immersion and spray drying techniques. Differential scanning calorimetry (DSC) thermograms of SY430 and SY350 samples exhibited melting point depressions indicating constricted crystallization inside the pores, whereas SY730 samples with melting points matching the pure API may be a result of surface crystallization. Powder x-ray diffraction (PXRD) diffractograms showed all crystalline samples matched the diffraction patterns of the pure API indicating no polymorphic transitions and all 3:1 ratio samples exhibited amorphous halo profiles. Response surface regression analysis and Classification and Regression Tree (CART) analysis suggest carrier to drug ratios, followed by molecular weight, have the most significant impact on the crystallinity of a drug loaded into MS particles.