The importance of intestinal residence time of absorption enhancer on drug absorption 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 and 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 sodium decanoate (SD) as the absorption enhancer. A secondary goal was to examine an erodible matrix formulation as a potential drug carrier for the synchronized release of two probes of different water solubilities. It was found that higher SCef blood levels were obtained after 30 min of co-administration 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 of enhancer perfusion, a finding which suggests that SCef requires a constant input of SD for its absorption which is more important than the concentration of SD administered. The feasibility of a hydroxypropyl methyl cellulose (HPMC) matrix for the synchronous release of two drug probes with different solubility properties was examined as a potential carrier to maintain constant levels of two drug probes over a predetermined period of time. (C) 1998 Elsevier Science B.V. All rights reserved.