Rojas-Oviedo I, Retchkiman-Corona B, Quirino-Barreda C T, Cárdenas J, Schabes-Retchkiman P S
Programa de Maestría en Ciencias Farmacéuticas, División de Ciencias Biológicas y de la Salud. Universidad Autónoma Metropolitana-Xochimilco. Calzada del Hueso 1100, Col. Villa Quietud. C.P. 04960 México, D.F., Mexico.
Indian J Pharm Sci. 2012 Nov;74(6):505-11. doi: 10.4103/0250-474X.110576.
Mechanochemical activation is a practical cogrinding operation used to obtain a solid dispersion of a poorly water soluble drug through changes in the solid state molecular aggregation of drug-carrier mixtures and the formation of noncovalent interactions (hydrogen bonds) between two crystalline solids such as a soluble carrier, lactose, and a poorly soluble drug, indomethacin, in order to improve its solubility and dissolution rate. Samples of indomethacin and a physical mixture with a weight ratio of 1:1 of indomethacin and lactose were ground using a high speed vibrating ball mill. Particle size was determined by electron microscopy, the reduction of crystallinity was determined by calorimetry and transmission electron microscopy, infrared spectroscopy was used to find evidence of any interactions between the drug and the carrier and the determination of apparent solubility allowed for the corroboration of changes in solubility. Before grinding, scanning electron microscopy showed the drug and lactose to have an average particle size of around 50 and 30 μm, respectively. After high speed grinding, indomethacin and the mixture had a reduced average particle size of around 5 and 2 μm, respectively, showing a morphological change. The ground mixture produced a solid dispersion that had a loss of crystallinity that reached 81% after 30 min of grinding while the drug solubility of indomethacin within the solid dispersion increased by 2.76 fold as compared to the pure drug. Drug activation due to hydrogen bonds between the carboxylic group of the drug and the hydroxyl group of lactose as well as the decrease in crystallinity of the solid dispersion and the reduction of the particle size led to a better water solubility of indomethacin.
机械化学活化是一种实际的共研磨操作，用于通过改变药物-载体混合物的固态分子聚集以及在两种结晶固体（如可溶性载体乳糖和难溶性药物吲哚美辛）之间形成非共价相互作用（氢键）来获得难溶性药物的固体分散体，以提高其溶解度和溶出速率。使用高速振动球磨机研磨吲哚美辛样品以及吲哚美辛与乳糖重量比为1:1的物理混合物。通过电子显微镜测定粒径，通过量热法和透射电子显微镜测定结晶度的降低，使用红外光谱寻找药物与载体之间任何相互作用的证据，并通过测定表观溶解度来证实溶解度的变化。研磨前，扫描电子显微镜显示药物和乳糖的平均粒径分别约为50和30μm。高速研磨后，吲哚美辛和混合物的平均粒径分别减小至约5和2μm，呈现出形态变化。研磨后的混合物形成了一种固体分散体，研磨30分钟后结晶度损失达到81%，而固体分散体中吲哚美辛的药物溶解度与纯药物相比增加了2.76倍。药物羧基与乳糖羟基之间的氢键导致的药物活化以及固体分散体结晶度的降低和粒径的减小，使得吲哚美辛具有更好的水溶性。
