Abstract
The present research encompasses a quality by design approach for fabricating lipid architectonics (LA) of an antiretroviral drug (Elvitegravir: EVR) to overcome inherent challenges of EVR to curtail its bioavailability issues. Comparative development strategy employing Box-Behnken design was undertaken between high-pressure homogenization technique and melt emulsification followed by probe sonication method, wherein the later was selected for engineering the EVR-LA. Particle size, entrapment efficiency and drug loading for EVR-LA were 84.6 ± 2.3nm, 90.7 ± 1.8% and 8.9 ± 0.7% respectively. In vitro release studies established the supremacy of EVR-LA when compared with drug suspension (EVR-DS) by having a cumulative drug release of 96.89 ± 2.5% in pH1.2, 89.84 ± 2.4% in pH6.8 and 86.64 ± 2.5% in pH7.4. Gut permeation studies revealed 19-fold increment in permeation by EVR-LA attributable to intrinsic permeation enhancing and efflux protein inhibitory activity of the lipids and surfactants incorporated. The result was validated by confocal study which exhibited enhanced permeation by EVR-LA. Dissolution study, conducted in fasted state simulated intestinal fluid (FaSSIF) and fed state simulated intestinal fluid (FeSSIF) media to ascertain the effect of food, demonstrated boosted absorption from FeSSIF media. Stability study was conducted in SGF pH1.2, FaSSIF and FeSSIF media. The lipolysis study, conducted to determine in vivo fate of EVR, revealed 27-fold increment in solubilization potential from EVR-LA (72.43 ± 2.6%). Thus, EVR-LA exhibited remarkable in vitro results by improving gut permeation and solubilization fate along with enhanced lymphatic uptake, thereby leading to prospective in vivo fate.
Published Version
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