Formulation and intestinal absorption enhancement evaluation of water-in-oil microemulsions incorporating medium-chain glycerides.
We developed self-emulsifying water-in-oil (w/o) microemulsions incorporating medium-chain glycerides and measured their conductance, viscosity, refractive index and particle size. Formulation of Calcein (a water-soluble marker molecule, MW = 623), or SK&F 106760 (a water-soluble RGD peptide, MW = 634) in a w/o microemulsion having a composition of Captex 355/Capmul MCM/Tween 80/Aqueous (65/22/10/3, % w/w), resulted in significant bioavailability enhancement in rats relative to their aqueous formulations. Upon intraduodenal administration the bioavailability was enhanced from 2% for Calcein in isotonic Tris, pH 7.4 to 45% in the microemulsion and from 0.5% for SK&F 106760 in physiological saline to 27% in the microemulsion formulation. The microemulsion did not induce gross changes in GI mucosa at a dosing volume of 3.3 ml/kg. These results suggest that water-in-oil microemulsion systems may be utilized for enhancement of intestinal drug absorption.
Department of Drug Delivery, Pharmaceutical Technologies, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939.
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Constantinides
J P
JP
Scalart
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Lancaster
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J
Marcello
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Marks
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Ellens
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PL
Smith
D015502:Absorptiometry, Photon; D000818:Animals; D001682:Biological Availability; D004553:Electric Conductivity; D004655:Emulsions / Q000737:chemistry*; D005452:Fluoresceins / Q000378:metabolism / Q000493:pharmacokinetics; D005989:Glycerides / Q000737:chemistry* / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D008859:Microscopy, Polarization; D009821:Oils / Q000737:chemistry; D010316:Particle Size; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012031:Refractometry; D013268:Stimulation, Chemical; D014783:Viscosity; D014867:Water / Q000737:chemistry
D004655:Emulsions; D005452:Fluoresceins; D005989:Glycerides; D009821:Oils; D010456:Peptides, Cyclic; D010975:Platelet Aggregation Inhibitors; D014867:Water; C071275:SK&F 106760; C007740:fluorexon