Sorbitol based powder precursor of cubosomes as an oral delivery system for improved bioavailability of poorly water soluble drugs

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.

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