Li Cai-Xia, Wang Hao-Bo, Oppong Daniel, Wang Jie-Xin, Chen Jian-Feng, Le Yuan
State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology , Beijing 100029, P. R. China.
Mol Pharm. 2014 Nov 3;11(11):4023-35. doi: 10.1021/mp500045t. Epub 2014 Oct 10.
Hydrophilic excipients can be used to increase the solubility and bioavailability of poorly soluble drugs. In this work, the conventional water-soluble pharmaceutical excipients hydroxypropylmethylcellulose (HPMC), polyvinylpyrrolidone (PVP), and lactose (LAC) were used as solid supports to prevent drug nanoparticles from aggregation and enhance drug dissolution. Excipient-assisted vinpocetine (VIN) nanoparticles were prepared by reactive precipitation. The analysis results indicated that HPMC was a suitable excipient to prepare VIN nanoparticles. VIN/HPMC nanoparticles had a mean size of 130 nm within a narrow distribution. The dissolution rate of VIN nanoparticles was significantly faster than those of a physical mixture of VIN/HPMC and raw VIN. VIN/HPMC nanoparticles had a higher dissolution profile than VIN/PVP and VIN/LAC nanoparticles. Besides, molecular dynamics (MD) simulation was applied to investigate the molecular interactions between VIN and excipients. The calculated results revealed that VIN interacted with excipients by Coulomb and Lennard-Jones (LJ) interactions. Few hydrogen bonds were formed between VIN and excipients. The HPMC affording smaller particle size may be a result of the stronger interactions between VIN and HPMC (mainly LJ interaction) and the property of HPMC. These characteristics may greatly influence the adsorption behavior and may be the crucial parameter for the better performance of HPMC.
亲水性辅料可用于提高难溶性药物的溶解度和生物利用度。在本研究中,传统的水溶性药用辅料羟丙基甲基纤维素(HPMC)、聚乙烯吡咯烷酮(PVP)和乳糖(LAC)被用作固体载体,以防止药物纳米颗粒聚集并提高药物溶解性能。通过反应沉淀法制备了辅料辅助的长春西汀(VIN)纳米颗粒。分析结果表明,HPMC是制备VIN纳米颗粒的合适辅料。VIN/HPMC纳米颗粒的平均粒径为130nm,粒径分布较窄。VIN纳米颗粒的溶解速率明显快于VIN/HPMC物理混合物和长春西汀原料药。VIN/HPMC纳米颗粒的溶出曲线高于VIN/PVP和VIN/LAC纳米颗粒。此外,应用分子动力学(MD)模拟研究了VIN与辅料之间的分子相互作用。计算结果表明,VIN与辅料通过库仑力和 Lennard-Jones(LJ)相互作用。VIN与辅料之间形成的氢键较少。HPMC能提供较小的粒径可能是由于VIN与HPMC之间较强的相互作用(主要是LJ相互作用)以及HPMC的性质所致。这些特性可能会极大地影响吸附行为,可能是HPMC表现更优的关键参数。