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

Hou, Yanting; Piao, Hongyu; Tahara, Yoshiro; Qin, Shouhong; Wang, Jingying; Kong, Qingliang; Zou, Meijuan; Cheng, Gang; Goto, Masahiro

doi:10.1016/j.ejps.2020.105521

Cited by 7 publications

(1 citation statement)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The everted gut sac model has also been used to investigate the role of pharmaceutical excipients and formulations in transport modulation. Surfactants, such as Cremophor EL, polysorbate 80 [ 98 ], Pluronic F68 [ 99 ], and TPGS [ 97 ] and formulations that include cyclodextrin inclusion complexes [ 100 ], nanoparticles [ 101 ], mixed-micellar proliposomal systems [ 102 ], nanodispersions [ 103 ], and solid lipid nanoparticles [ 43 ] of P-gp substrates can be screened using the everted sac model. The reproducible results of this in vitro model suggest its usefulness for transport studies of P-gp substrates and potential P-gp inhibitors.…”

Section: Mechanism Of P-gp Efflux and Functions Of P-gpmentioning

confidence: 99%

Pharmaceutical Formulations with P-Glycoprotein Inhibitory Effect as Promising Approaches for Enhancing Oral Drug Absorption and Bioavailability

2021

View full text Add to dashboard Cite

P-glycoprotein (P-gp) is crucial in the active transport of various substrates with diverse structures out of cells, resulting in poor intestinal permeation and limited bioavailability following oral administration. P-gp inhibitors, including small molecule drugs, natural constituents, and pharmaceutically inert excipients, have been exploited to overcome P-gp efflux and enhance the oral absorption and bioavailability of many P-gp substrates. The co-administration of small molecule P-gp inhibitors with P-gp substrates can result in drug–drug interactions and increased side effects due to the pharmacological activity of these molecules. On the other hand, pharmaceutically inert excipients, including polymers, surfactants, and lipid-based excipients, are safe, pharmaceutically acceptable, and are not absorbed from the gut. Notably, they can be incorporated in pharmaceutical formulations to enhance drug solubility, absorption, and bioavailability due to the formulation itself and the P-gp inhibitory effects of the excipients. Different formulations with inherent P-gp inhibitory activity have been developed. These include micelles, emulsions, liposomes, solid lipid nanoparticles, polymeric nanoparticles, microspheres, dendrimers, and solid dispersions. They can bypass P-gp by different mechanisms related to their properties. In this review, we briefly introduce P-gp and P-gp inhibitors, and we extensively summarize the current development of oral drug delivery systems that can bypass and inhibit P-gp to improve the oral absorption and bioavailability of P-gp substrates. Since many drugs are limited by P-gp-mediated efflux, this review is helpful for designing suitable formulations of P-gp substrates to enhance their oral absorption and bioavailability.

show abstract