Solid-in-oil nanodispersions as a novel delivery system to improve the oral bioavailability of bisphosphate, risedronate sodium

Abstract

The aim of the current study was to modify the oral absorption of risedronate sodium (RS) using solid-in-oil nanodispersions (SONDs) technology. The oral therapeutic effect of RS is limited in vivo because of its low membrane permeability and the formation of insoluble precipitates with bivalent cations (such as Ca2+) in the gastrointestinal (GI) tract.We used SONDs to prepare medium-chain triglyceride (MCT)-based nanodispersions of the hydrophilic drug, which used the oral absorption mechanism of MCT digestion to improve bioavailability of RS in vivo. SONDs exhibited high encapsulation efficiency of RS and excellent enzymatic degradation-dependent release behavior. The result of an everted gut sac test showed that the Papp value of the SONDs was 6.29-fold (p<0.05) higher than that of RS aqueous solutions in simulated intestinal fluid containing 5 mM Ca2+, this was because MCT can be digested to form the fatty acids C8 and C10, which have an adsorption-promoting effect on RS. Further, solid-in-oil-in-water (S/O/W) emulsion droplets formedafter emulsification by bile salts and MCT digestionwere effective in disrupting epithelial tight junctions (TJs), facilitating the paracellular permeation of RS throughout the intestine. Moreover, in vivo absorption study in rats revealed that the AUC0-12h of RS in SONDs was approximately 4.56-fold (p<0.05) higher than with RS aqueous solutions at the same dose (15 mg/kg). This approach demonstrates a potential drug delivery system to improve the bioavailability of risedronate sodium.