EFFECT OF POLYCARBOPHIL CONCENTRATION ON IN-VITRO RELEASE AND IN-VIVOAVAILABILITY IN BEAGLE DOGS OF DIHYDROERGOTAMINE MESYLATE SUPPOSITORIES

The effect of different concentrations (5, 10 and 20% w/w) of polycarb ophil on the in vitro release and in vivo availability of dihydroergot amine mesylate from polyethylene glycol suppositories was studied. In vitro release data showed that as the polycarbophil concentration in t he suppositories increased, the release rate decreased. The in vivo da ta revealed that suppositories containing 5% polycarbophil resulted in a significant (p < 0.05) reduction in C-max and non-significant decre ase in AUC and produced 62% relative bioavailability compared to that of polyethylene glycol suppositories containing 0% polycarbophil (cont rol). The addition of 10% polycarbophil to the suppository formulation resulted in a lower reduction in C-max and AUC than the addition of 5 % and gave 78.9% relative bioavailability. The suppositories containin g 20% polycarbophil produced higher C-max, AUG, and relative bioavaila bility (127%) compared to the control, The concentration of polycarbop hil in dihydroergotamine suppository formulations is critical in deter mining the release rate of the:drug and its bioavailability.