Enhancing the Solubility and Oral Bioavailability of Poorly Water-Soluble Drugs Using Monoolein Cubosomes.

Abstract

Monoolein cubosomes containing either spironolactone (SPI) or nifedipine (NI) were prepared using a high-pressure homogenization technique and characterized in terms of their solubility and oral bioavailability. The mean particle size, polydispersity index (PDI), zeta potential, solubility and encapsulation efficiency (EE) values of the SPI- and NI-loaded cubosomes were determined to be 90.4 nm, 0.187, -13.4 mV, 163 µg/mL and 90.2%, and 91.3 nm, 0.168, -12.8 mV, 189 µg/mL and 93.0%, respectively, which were almost identical to those of the blank cubosome. Small-angle X-ray scattering analyses confirmed that the SPI-loaded, NI-loaded and blank cubosomes existed in the cubic space group Im3̄m. The lattice parameters of the SPI- and NI-loaded cubosomes were 147.6 and 151.6 Å, respectively, making them almost identical to that of blank cubosome (151.0 Å). The in vitro release profiles of the SPI- and NI-loaded cubosomes showed that they released less than 5% of the drugs into various media over 12-48 h, indicating that most of the drug remained encapsulated within the cubic phase of their lipid bilayer. Furthermore, the in vivo pharmacokinetic results suggested that these cubosomes led to a considerable increase in the systemic oral bioavailability of the drugs compared with pure dispersions of the same materials. Notably, the stability results indicated that the mean particle size and PDI values of these cubosomes were stable for at least 4 weeks. Taken together, these results demonstrate that monoolein cubosomes represent promising drug carriers for enhancing the solubility and oral bioavailability of poorly water-soluble drugs.