Rectal delivery system for insulin

The purpose of this investigation was to first screen for potential effectiveness several rectal gels as insulin delivery systems and to select one promising dosage form as candidate for further evaluation in rabbits and man. Criteria for effectiveness were the "pharmacologic availability", determined as the ratio between the total area under the percent glucose reduction versus time curves upon rectal administration and the standard (I.V. for rabbits and S.C. for man), the maximum reduction in glucose blood concentration, the time to reach the maximum and the mean residence time of glucose reduction. The rectal gels consisted of emulsion systems prepared from pH 8 buffer solution containing insulin, an oleaginous phase, a surface active agent (bile salts, Myrj or Brij), and a viscosity increasing agent. The finally selected rectal gel was tested in rabbits both in a parallel and a crossover design in nondiabetic and diabetic animals. The selected rectal gel in nondiabetic and diabetic rabbits resulted in a pharmacologic availability of about 25%. By addition of Azone the pharmacologic availability was further increased, although not significantly (small n). In nondiabetic man the pharmacologic availability was about 32%, whereas the bioavailability (measured from plasma insulin) was only about 11%. Drugs undergoing hepatic first-pass metabolism and for which the liver is the biophase, should show increased pharmacologic availability with decreased bioavailability (if the latter one is due to first-pass effect).