Nano-sized water-in-oil-in-water emulsion enhances intestinal absorption of calcein, a high solubility and low permeability compound.
Our goal was to develop safe and stable multilayer emulsions capable of enhancing intestinal absorption of biopharmaceutics classification system (BCS) class III drugs. First, w/o emulsions were prepared using calcein as a model BCS class III compound and condensed ricinoleic acid tetraglycerin ester as a hydrophobic emulsifier. Then water-in-oil-in-water (w/o/w) emulsions were prepared with shirasu porous glass (SPG) membranes. Particle size analyses and calcein leakage from oil droplets in w/o/w emulsions led us to select stearic acid hexaglycerin esters (HS-11) and Gelucire 44/14 as hydrophilic emulsifiers. Analyses of the absorption-enhancing effects of w/o/w emulsions on intestinal calcein absorption in rats showed that calcein bioavailability after intraduodenal (i.d.) administration of HS-11 or Gelucire 44/14+polyvinyl alcohol (PVA) w/o/w emulsions prepared with 0.1-microm pore-sized SPGs was significantly higher than that of the calcein control. However, serum calcein concentration vs. time profiles after i.d. administration of w/o/w emulsions prepared with 1.1-microm and 30-microm pore-sized SPGs and an emulsion prepared with a calcein-containing outer water phase were comparable to control profiles. These results suggested that HS-11 or Gelucire 44/14+PVA are safe outer water phase additives and that 0.1-microm pore-sized SPGs are important for preparing w/o/w emulsions that enhanced intestinal calcein absorption.
Koga
Kenjiro
K
Department of Clinical Pharmaceutics, Hokuriku University, Kanazawa, Japan. k-koga@hokuriku-u.ac.jp
Takarada
Nobuo
N
Takada
Kanji
K
D000818:Animals; D001682:Biological Availability; D004337:Drug Carriers / Q000009:adverse effects / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D004339:Drug Compounding / Q000295:instrumentation / Q000379:methods; D004355:Drug Stability; D045703:Emulsifying Agents / Q000009:adverse effects / Q000737:chemistry; D004655:Emulsions / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D005452:Fluoresceins / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D007583:Jejunum / Q000187:drug effects / Q000473:pathology; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004337:Drug Carriers; D045703:Emulsifying Agents; D004655:Emulsions; D005452:Fluoresceins; C007740:fluorexon