Physiological Pharmaceutics

Colon and rectal drug delivery 169Figure 7.12 Spreading of liquid and foam enema after rectal administration(25%). Consequently it appears that increasing the administered volume causes the dose tospread more effectively into the colon.In an attempt to increase the penetration of small volumes of liquid, foam enemashave been studied 121 . However retrograde spreading of foams was lower than solutionenemas, being limited to the sigmoid colon (Figure 7.12).Therapeutic agents administered rectallyAnticonvulsantsTraditionally the need for rapid attainment of a therapeutic blood concentration of a drughas meant that intravenous drug delivery has been the only method available for thetreatment of status epilepticus or serial seizures. However, the technical problems associatedwith intravenous administration have prompted the evaluation of rectal dosage forms as apractical alternative.Diazepam is rapidly absorbed from rectally delivered solution in propyleneglycolwater-ethanol in healthy volunteers 122 . Suppository formulations of diazepam appearto be effective and safe in the prevention of recurrent febrile convulsions in children,suggesting that formulations with non-instantaneous release may be adequate forprophylactic therapy 123 . In adult epileptic patients, 10mg of diazepam in 2ml of anintravenous solution was administered rectally, and this resulted in serum concentrationscomparable with those obtained after oral administration of a 10mg tablet; absolute rectalbioavailability amounted to 81% 124 . ‘ Valium’ suppositories however have a bioavailabilityof just less than 70%, but have a very slow rate of absorption, with a T maxranging from 90to 480 mins 125 .Clonazepam, rectally administered as a suspension in 2.2 to 3.8ml of a propyleneglycol-water mixture, also containing acetic acid, ethanol and benzylalcohol (Rivotril)