Abstract
The objective of this study was to develop sorbitol based powder precursor of cubosomes loaded with tamoxifen citrate (TC), as a model of poorly water soluble drug, aimed at enhancing its oral bioavailability. TC-loaded powder precursor formulations were prepared by sequential spraying of TC/glycerol monooleate (GMO)/poloxamer 407 solution onto the surface of sorbitol powder. Four formulations (F1, F2, F3 and F4) were prepared at four GMO: sorbitol ratios of 1:2.5, 1:5, 1:7.5 and 1:10 w/w, respectively. The prepared powder precursors were subjected to in vitro and in vivo characterization. In vitro, direct correlations were observed between GMO: sorbitol ratio and % yield, drug content, flowability and dissolution efficiency of TC-loaded powder precursors. TC-loaded cubosomes, derived from the prepared powder precursors, exhibited a size range of 67.34 +/- 4.40-102.01 +/- 4.86 nm and entrapped more than 95% TC. In vivo absorption study in rats showed improved rate and extent of TC absorption from drug loaded powder precursor (F4) compared to those of plain TC powder, with evidence of a relative bioavailability of 152.50 +/- 32.67%. In conclusion, sorbitol based powder precursor of cubosomes may be a promising oral delivery system for enhancing the bioavailability of poorly water soluble drugs. (C) 2016 Elsevier B.V. All rights reserved.