title: Self-double-emulsifying drug delivery system (SDEDDS): a new way for oral delivery of drugs with high solubility and low permeability.
abstract: Water-in-oil-in-water (w/o/w) double emulsions are potential for enhancing oral bioavailability of drugs with high solubility and low permeability, but their industrial application is limited due to the instability. Herein, we developed a novel formulation, self-double-emulsifying drug delivery systems (SDEDDS) by formulating mixtures of hydrophilic surfactants and water-in-oil (w/o) emulsions, which were easier to be stable through formulations optimization. SDEDDS can spontaneously emulsify to water-in-oil-in-water (w/o/w) double emulsions in the mixed aqueous gastrointestinal environment, with drugs encapsulated in the internal water phase of the double emulsions. We employed SDEDDS to improve the oral absorption of pidotimod, a peptide-like drug with high solubility and low permeability. The optimized pidotimod-SDEDDS were found to be stable up to 6 months under 25°C. Plasma concentration-time profiles from pharmacokinetic studies in rats dosed with SDEDDS showed 2.56-fold (p<0.05) increased absorption of pidotimod, compared to the pidotimod solution. Histopathologic studies confirmed that SDEDDS exerted absorption promoting effect without serious local damages. These studies demonstrate that SDEDDS may be a promising strategy for peroral delivery of peptide and peptidomimetic drugs.
authors.affiliation: Pharmaceutical Research Institute, China Pharmaceutical University, 24 Tongjia Street, Nanjing, Jiangsu Province 210009, China.
authors.forename: Xiaole
authors.initials: X
authors.lastname: Qi
authors.forename: Lishuang
authors.initials: L
authors.lastname: Wang
authors.forename: Jiabi
authors.initials: J
authors.lastname: Zhu
authors.forename: Zhenyi
authors.initials: Z
authors.lastname: Hu
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D016503:Drug Delivery Systems; D004355:Drug Stability; D004356:Drug Storage; D004655:Emulsions; D008297:Male; D010539:Permeability; D011761:Pyrrolidonecarboxylic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry*; D053778:Thiazolidines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D004655:Emulsions; D013501:Surface-Active Agents; D053778:Thiazolidines; C064893:pidotimod; D011761:Pyrrolidonecarboxylic Acid