Effect of oils on drug absorption
Oil and emulsion vehicles have been shown to alter the oral absorption of many drugs. This may be due to enhanced lymph flow and/or altered gastro-intestinal motility in the presence of the oils. The oral absorption of a model compound (DOT) in the presence of three chemically different oils, arachis oil, Miglyol 812 and liquid paraffin was investigated in rats, the influence of lymphatic absorption and gastro-intestinal motility being determined. The findings were applied to the for.mulation of the'steroid prednisolone, in an attempt to produce elevated more uniform plasma drug levels by enhancing lymphatic absorption. The rank order for total DOT absorption from 1m! Volumes of different vehicles was arachis oil > Miglyol 812= water containing 6% Tween 80 > liquid paraffin. The concentration of DDT in lymph collected via thoracic duct cannblae in anaesthetised rats was greatest in the presence of arachis oil, there being no difference between Miglyol 812 and liquid paraffin. Using a gamma camera the gastric emptying rate and total intestinal transit of 9~c-sulphur colloid, an oil phase marker, was shown to be faster in the presence of 1ml liquid paraffin than the other two oils. The oral absorption of 3H-prednisolone was independent of the nature of the oily vehicle (30pl volumes) and was not selectively absorbed into the lymph. Esterification to 3H-prednisolone-21-palmitate increased the lipophilicity of the drug but did not stimulate selective lymphatic absorption and reduced oral absorption following administration in arachis oil. Lymphatic absorption of the ester was not promoted by administration in 1ml arachis oil. Only the lymphatic absorption of compounds exhibiting selective uptake into the lymph may be enhanced by the presence of a suitable lipid vehicle. Altered gastro-intestinal motility in the presence of lipids may have greater potential for enhancing the absorption of a wider variety of compounds.