Novel gels and their dispersions - oral drug delivery systems for ciclosporin

Amphiphilogels (gels that consist solely of surfactants) and gel-based emulsion (GEM) formulations (solutions that gel upon incorporation of small amounts of water) were investigated as oral delivery vehicles for ciclosporin A, in in vivo experiments in Beagle dogs. Both systems represent essentially self-dispersing non-lipidic drug delivery systems based on amphiphilic surfactants. Three different amphiphilogels (hydrophobic, hydrophilic and hydrophilic gel containing ethanol), the aqueous dispersions of the latter two amphiphilogels and of two GEM formulations were tested to determine the influence of (i) gel hydrophilicity/hydrophobicity, (ii) presence of ethanol, (iii) pre-dispersion of gels into aqueous medium prior to oral administration and (iv) size of dispersions, on drug absorption. It was found that all the formulations tested, except for the hydrophilic amphiphilogel and its aqueous dispersion, were bioequivalent to Neoral (R), the commercially available preparation. High drug absorption from the bioequivalent formulations was thought to be due to the fact that following oral administration, ciclosporin remained in a soluble form, hence was available for absorption, despite relatively large droplet sizes of the formulations. The hydrophilic gel and its dispersion allowed less drug absorption; this was assigned to the fact that, when the hydrophilic amphiphilogel contacted an aqueous medium, there were no lipophilic domains in which the drug could remain soluble. It is possible that some drug precipitated out and was unavailable for absorption. (c) 2005 Elsevier B.V. All rights reserved.