Abstract：
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.
摘要：
本研究旨在研究以介孔二氧化硅为载体制备无定形固体分散体的BCSII类药物的无定形稳定性。布洛芬,非诺贝特,选择布地奈德作为模型药物，以评估分子量和分配系数对载药介孔二氧化硅（MS）颗粒固态的影响。将模型药物装入三个等级的MS，SYLYSIASY730，SYLYSIASY430和SYLYSIASY350，孔径为2.5nm，17nm,和21纳米，分别,1:3、1:2和3:1，载体与药物的比例，和使用溶剂浸渍和喷雾干燥技术的三种不同的负载浓度。SY430和SY350样品的差示扫描量热法（DSC）热谱图显示熔点下降，表明孔内结晶收缩，而熔点与纯API相匹配的SY730样品可能是表面结晶的结果。粉末X射线衍射(PXRD)衍射图显示所有结晶样品与纯API的衍射图案匹配,表明没有多晶型转变,并且所有3:1比率的样品显示无定形晕轮分布。响应面回归分析和分类回归树(CART)分析表明，载体与药物的比例，其次是分子量，对装载到MS颗粒中的药物的结晶度具有最显著的影响。
