College of Pharmacy, Chung-Ang University, Seoul, 155-756, Korea.
Arch Pharm Res. 2013 Nov;36(11):1369-76. doi: 10.1007/s12272-013-0187-2. Epub 2013 Jun 20.
While the number and diversity of lead compounds has increased with the development of science technologies, ca. 90 % of new chemical entities under development have shown low aqueous solubility, classified as class II or IV of the biopharmaceutics classification system (BCS). The low aqueous solubility hinders their clinical translations due to low bioavailability and dissolution-limited absorption of orally-administered drugs. Several technologies have been employed to improve the solubility of poorly water-soluble drugs. In this paper, a new method of nanoparticulation using fat and a supercritical fluid (NUFS) for the formulation of hydrophobic drugs was applied to solve the low solubility problem. A typical BCS class II drug, itraconazole, was selected and formulated with hydroxypropyl methylcellulose, emulsification, and anticoagulating agents for NUFS. The non-spherical itraconazole nanoparticles prepared by NUFS were ~300-500 nm in size with a ~15-fold improved dissolution rate compared to non-nanoparticles of itraconazole (i.e., raw itraconazole). In addition, a high drug content of ~46 % by weight and a drug loading efficiency greater than 85 % were achieved. Therefore, the new technology for nano-platforms could be a promising solution for solubilization of poorly water-soluble drugs, resulting in improved bioavailability.
随着科学技术的发展，先导化合物的数量和种类有所增加，但约 90%的新化学实体的开发显示出低水溶解度，被归类为生物药剂学分类系统（BCS）的 II 类或 IV 类。低水溶解度由于口服药物的生物利用度低和溶解限制吸收而阻碍了它们的临床转化。已经采用了几种技术来提高难溶性药物的溶解度。在本文中，使用脂肪和超临界流体（NUFS）的纳米粒化新方法被应用于解决低溶解度问题。选择典型的 BCS II 类药物伊曲康唑，并与羟丙基甲基纤维素、乳化剂和抗凝剂一起用于 NUFS 配方。通过 NUFS 制备的非球形伊曲康唑纳米颗粒的尺寸约为 300-500nm，与伊曲康唑的非纳米颗粒（即原伊曲康唑）相比，其溶解速率提高了约 15 倍。此外，实现了约 46%重量的高药物含量和大于 85%的药物载药量。因此，用于纳米平台的新技术可能是解决难溶性药物溶解度问题的有前途的解决方案，从而提高生物利用度。
