Evaluation of Gastrointestinal Transit Characteristics of Oral Patch Preparation Using Caffeine as a Model Drug in Human Volunteers

Salivary caffeine excretion rate test has been proposed for the evaluation of gastrointestinal transit characteristics of an oral patch preparation after administration to human volunteers instead of measuring the plasma or serum concentration in the early stages of formulation development. Patches having a diameter of 3.0mm and containing caffeine as a model drug were prepared. The patches consisted of 1) the backing layer made of a water-insoluble polymer, 2) the drug-carrying layer composed of caffeine and a gel-forming polymer, and 3) the enteric polymer membrane. These three layer patches were filled into enteric capsules. Caffeine solution in an enteric capsule was used as the control preparation. After oral administration of each preparation to human volunteers at a dose of 50mg of caffeine in a cross-over study with a wash-out period of two weeks, saliva samples were collected over 1min at every sampling time for 12h and salivary caffeine concentration was determined by a HPLC assay method. Salivary caffeine excretion rate (ER) was used for pharmacokinetic analysis. Mean residence time (MRT) and first-appearance time of caffeine into the saliva (Ti) were determined. To characterize the pharmacokinetics of caffeine, MRT-Ti values of patch and solution preparations were compared. Patch preparations had a Ti value of 2.33±0.33h and showed significantly longer MRT-Ti, 3.87±0.21h, as compared to the control preparation (MRT-Ti=1.04±0.38h) under fasting condition (p