Novel pectin-based nanoparticles prepared from nanoemulsion templates for improving in vitro dissolution and in vivo absorption of poorly water-soluble drug.

The purpose of this study was to improve in vitro dissolution and in vivo absorption of itraconazole (ITZ), a poorly water-soluble drug, by means of novel pectin-based nanoparticles prepared from nanoemulsion templates. Nanoemulsion templates were prepared by a high-pressure homogenization using pectin (i.e., 0.5-3.0%w/w low-methoxyl pectin (LMP), amidated low-methoxyl pectin (ALMP), or high-methoxyl pectin (HMP)) as an emulsifier and chloroform as an oil phase. HMP provided good oil-in-water emulsions with ITZ loaded in the oil phase. The chloroform in nanoemulsions was then removed to produce the suspensions of nanoparticles dispersed in water phase. After lyophilization, the dried core-shell nanoparticles with good properties in terms of redispersibility, dissolution, and stability were obtained. The alteration of ITZ crystallinity was clearly observed from powder X-ray diffractogram while no interaction between ITZ and pectin was found in the nanoparticles. The ITZ-loaded nanoparticles showed high percent drug dissolved, especially those prepared from HMP, and could maintain their good dissolution properties even after 6-month storage. The in vivo absorption study in fasted rats demonstrated that pectin-based nanoparticles prepared from nanoemulsion templates could improve absorption of ITZ, that is, 1.3-fold higher than the ITZ commercial product (p<0.05). Pectin type highly influenced the dissolution properties and also in vivo plasma profile. These findings suggested that HMP-based nanoparticles seem to be a promising formulation due to their high AUC(0-24h) and C(max).