Watanabe Tomoyuki, Hasegawa Susumu, Wakiyama Naoki, Kusai Akira, Senna Mamoru
Product Development Laboratories, Sankyo Co. Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
Int J Pharm. 2003 Jan 2;250(1):283-6. doi: 10.1016/s0378-5173(02)00549-5.
States of interaction between indomethacin (IM) and polyvinylpyrrolidone (PVP) in an amorphous solid dispersion prepared by co-grinding were compared with those between IM and silica nanoparticles. Changes in the carbon chemical states of the solid dispersions were evaluated based on the chemical shift in the 13C-CP/MAS-NMR. Hydrogen bonds between the amide carbonyl of PVP particles and the carboxyl groups of IM molecules were formed by co-grinding. Despite the wide difference in carrier properties, the apparent equilibrium solubility (AES) of IM in the ground IM-PVP mixture was predicted by solid state NMR on the basis of the relationship previously established for IM with SiO(2). This indicates that AES is affected solely by the state of IM, irrespective of the carrier species, and despite carrier-dependent chemical interactions.
将通过共研磨制备的非晶态固体分散体中印多酸(IM)与聚乙烯吡咯烷酮(PVP)之间的相互作用状态,与IM和二氧化硅纳米颗粒之间的相互作用状态进行了比较。基于13C-CP/MAS-NMR中的化学位移评估了固体分散体中碳化学状态的变化。通过共研磨在PVP颗粒的酰胺羰基与IM分子的羧基之间形成了氢键。尽管载体性质差异很大,但基于先前建立的IM与SiO₂的关系,通过固态NMR预测了IM在研磨后的IM-PVP混合物中的表观平衡溶解度(AES)。这表明AES仅受IM状态的影响,与载体种类无关,尽管存在依赖于载体的化学相互作用。