Abstract Abiraterone acetate (ABA) belongs to low permeability low solubility class. It exhibits pH-dependent solubility with slightly better solubility at gastric pH. It may thus undergo supersaturation and precipitation after gastric emptying. ABA may undergo premature hydrolysis in intestinal lumen which decreases the amount absorbed. This can contribute to its low bioavailability. The aim was to formulate ABA in self-emulsifying drug delivery system (SEDDS), which was loaded in in situ gelling system made of alginate or alginate and chitosan. This can provide controlled release of ABA, preventing possible precipitation with SEDDS augmenting absorption. Alginate and alginate-chitosan based formulations were developed based on gelling capacity. SEDDS comprising oleic acid with Tween 80 and glycerol was fabricated and loaded into in situ gelling formulations. The release behavior was monitored using continuous pH variation. The oral bioavailability of ABA was assessed indirectly by monitoring rat total serum testosterone level. Results indicated that both increasing the concentration of alginate and adding chitosan contributed to enhanced gelation. Loading ABA in SEDDS hastened its dissolution. Loading into in situ gelling system resulted in controlled release with alginate-chitosan system showing better retention of ABA in stomach and intestinal phases. The total serum testosterone level was 8.18, 3.43, 1.51, 3.4 and 0.25 ng/ml for control rat, rats receiving ABA aqueous suspension, ABA in SEDDS, ABA SEDDS in 1% alginate and ABA SEDDS in 1% alginate/1% chitosan. The results suggested that SEDDS can prevent premature degradation and controlling the release within the stomach and intestine maximize the efficacy. Graphical Abstract
Shehata et al. (Mon,) studied this question.