The importance of intestinal residence time of absorption enhancer on drugabsorption and implication on formulative considerations

Absorption enhancers are efficient in small body cavities such as the nasal and the rectum. However, in the gastrointestinal tract, where the volume a nd amount of liquids are large and motility is more profound, dilution may require a constant input of the enhancer with a poorly absorbed drug. Using a perfused rat model, the purpose of the present study was to verify that the synchronized administration of a poorly absorbed drug and an absorption enhancer is required for optimal drug absorption after oral administration . Sodium cefazoline (SCef) was used as the poorly absorbed drug probe and s odium decanoate (SD) as the absorption enhancer. A secondary goal was to ex amine an erodible matrix formulation as a potential drug carrier for the sy nchronized release of two probes of different water solubilities. It was fo und that higher SCef blood levels were obtained after 30 min of co-administ ration of 50 mM of SD, than after co-administration of 100 mM over 15 min. In both cases SCef blood levels declined within 15-30 min after cessation o f enhancer perfusion, a finding which suggests that SCef requires a constan t input of SD for its absorption which is more important than the concentra tion of SD administered. The feasibility of a hydroxypropyl methyl cellulos e (HPMC) matrix for the synchronous release of two drug probes with differe nt solubility properties was examined as a potential carrier to maintain co nstant levels of two drug probes over a predetermined period of time. (C) 1 998 Elsevier Science B.V. All rights reserved.