The study aims to develop and optimise lipid-based colloidal carriers (LBCC) for enhancing
solubilisation and reducing fed/fasted variation for the poorly water-soluble danazol (DAN). Oil-based and
self-microemulsifying delivery systems (SMEDDS) were developed, and the effect of solidification was investigated.
Liquid SMEDDS (L-SMEDDS, Capmul MCM:Tween 80:Transcutol HP 1:2:1, w/w) and emulsion
(Capmul MCM:soya lecithin 100:0.6, w/w) were developed. Solid-state formulations were prepared via
(i) physical adsorption of L-SMEDDS (P-SMEDDS) or (ii) spray drying of emulsion (silica-lipid hybrid, SLH) and
L-SMEDDS (spray-dried SMEDDS, S-SMEDDS) using Aerosil 380 silica nanoparticles as the solid carrier. In vitro lipid
digestion and drug solubilisation under simulated intestinal conditions in both fasted and fed states were investigated.
Solubilisation of unformulated DAN under both fasted and fed conditions was low, and a large fed/fasted variation was
observed, i.e. 6.6-fold difference. All LBCC formulations provided enhanced drug solubilisation and significantly reduced
the fed/fasted variation. For self-emulsifying LBCC, the fasted state drug solubilisation was ranked as L-SMEDDS > PSMEDDS
> S-SMEDDS, suggesting that solidification reduced the capability of SMEDDS in presenting DAN to the
aqueous phase. However, in the case of oil-based LBCC, improved drug solubility was observed with the solid form SLH
under both fasted and fed state in comparison to that of the equivalent liquid form. Overall, the SLH, which provided the
highest drug solubilisation in the fasted state (i.e. 10-fold higher than the pure DAN) and the smallest fed/fasted variation,
was considered an optimised solid LBCC to enhance the solubilisation of DAN and reduce the fed/fasted variation.
Keywords: Colloidal carriers, fasted state, fed state, food effect, in vitro lipolysis, lipid-based, self-microemulsifying, silicalipid
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