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Enhanced dissolution and oral absorption of tacrolimus by supersaturable self-emulsifying drug delivery system

A new Soluplus (polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer)-based supersaturable self-emulsifying drug delivery system (S-SEDDS) was formulated to enhance oral absorption of tacrolimus (FK506) with minimal use of oil, surfactant, and cosurfactant. A high payload supe...

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Detalles Bibliográficos
Autores principales: Lee, Dae Ro, Ho, Myoung Jin, Jung, Hyuck Jun, Cho, Ha Ra, Park, Jun Seo, Yoon, Suk-Hyun, Choi, Yong Seok, Choi, Young Wook, Oh, Chung-Hun, Kang, Myung Joo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807944/
https://www.ncbi.nlm.nih.gov/pubmed/27051286
http://dx.doi.org/10.2147/IJN.S102991
Descripción
Sumario:A new Soluplus (polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer)-based supersaturable self-emulsifying drug delivery system (S-SEDDS) was formulated to enhance oral absorption of tacrolimus (FK506) with minimal use of oil, surfactant, and cosurfactant. A high payload supersaturable system (S-SEDDS) was prepared by incorporating Soluplus, as a precipitation inhibitor, to SEDDS consisting of Capmul MCM, Cremophor EL, and Transcutol (FK506:vehicle:Soluplus =1:15:1). In vitro dissolution profile and in vitro pharmacokinetic aspect of S-SEDDS in rats were comparatively evaluated with those of conventional SEDDS formulas containing four times greater content of vehicle components (FK506:vehicle =1:60). Both formulations formed spherical drug-loaded microemulsion <70 nm in size when in contact with aqueous medium. In an in vitro dissolution test in a nonsink condition, the amphiphilic polymer noticeably retarded drug precipitation and maintained >80% of accumulated dissolution rate for 24 hours, analogous to that from conventional SEDDS. Moreover, pharmacokinetic parameters of the maximum blood concentration and area under the curve from S-SEDDS formula in rats were not statistically different (P>0.05) than those of conventional SEDDS. The results suggest that the Soluplus-based supersaturable system can be an alternative to achieve a comparable in vitro dissolution profile and in vivo oral absorption with conventional SEDDS, with minimal use of vehicle ingredients.