A nanosystem for water-insoluble drugs prepared by a new technology, nanoparticulation using a solid lipid and supercritical fluid

Abstract

While the number and diversity of lead compounds has increased with the development of science technologies, ca. 90 % ofnewchemical 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-administereddrugs. Several technologies have been employed to improve the solubility of poorly water-solubledrugs. In this paper, anewmethod ofnanoparticulationusing fat and asupercriticalfluid(NUFS) for the formulation of hydrophobicdrugswas 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 nanoparticlespreparedby 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, thenewtechnologyfor nano-platforms could be a promising solution for solubilization of poorly water-solubledrugs, resulting in improved bioavailability.