New Jersey Center for Engineered Particulates, New Jersey Institute of Technology, Newark, NJ 07102, USA.
New Jersey Center for Engineered Particulates, New Jersey Institute of Technology, Newark, NJ 07102, USA.
Int J Pharm. 2021 Sep 5;606:120853. doi: 10.1016/j.ijpharm.2021.120853. Epub 2021 Jul 10.
The impact of dry coating with hydrophobic or hydrophilic nano-silica at 25-100% surface area coverage on dissolution of micronized poorly water-soluble drugs was investigated by examining their agglomeration and surface hydrophobicity. Ibuprofen (20 µm and 10 µm) and griseofulvin (10 µm) were selected having differing solubility, hydrophobicity, and surface morphology. Characterization involved particle agglomeration via two dry dispersion methods, drug dissolution using the USP IV method, cohesion reduction through shear testing, and powder wettability via the modified Washburn method. Dry coating dramatically reduced the cohesion hence agglomerate size of both the coated ibuprofen particles, but less for griseofulvin, attributed to its surface morphology. For hydrophobic silica, agglomerate size reduction outweighed the adverse impact of increased surface hydrophobicity for ibuprofen. For griseofulvin, the agglomerate reduction was much lower, not able to overcome the effect of increased drug particle hydrophobicity with hydrophobic silica coating. Hydrophilic silica coating reduced hydrophobicity for all three drug powders, leading to the synergistic improvement in the dissolution along with agglomerate size reduction. Overall, the combined effect of the drug particle surface hydrophobicity and agglomerate size, represented by specific surface area, could explain the dissolution behavior of these poorly water-soluble drugs.
通过考察微米化的疏水性药物的团聚和表面疏水性，研究了在 25-100%表面积覆盖率下用疏水性或亲水性纳米二氧化硅干法包衣对药物溶出的影响。选择具有不同溶解度、疏水性和表面形态的布洛芬（20 µm 和 10 µm）和灰黄霉素（10 µm）。表征涉及两种干法分散方法的颗粒团聚，采用 USP IV 法进行药物溶出，通过剪切试验降低内聚，采用改良的 Washburn 法测定粉末润湿性。干法包衣显著降低了两种包衣布洛芬颗粒的内聚，从而减小了团聚体的大小，但对灰黄霉素的影响较小，这归因于其表面形态。对于疏水性二氧化硅，团聚体尺寸的减小大于增加表面疏水性对布洛芬的不利影响。对于灰黄霉素，团聚体的减少要低得多，不能克服疏水性二氧化硅包衣增加药物颗粒疏水性的影响。亲水性二氧化硅包衣降低了所有三种药物粉末的疏水性，从而协同改善了溶出度和团聚体尺寸的减小。总体而言，药物颗粒表面疏水性和团聚体尺寸（以比表面积表示）的综合效应可以解释这些疏水性差的药物的溶解行为。
