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 3.0 mm 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 50 mg of caffeine in a cross-over study with a wash-out period of two weeks, saliva samples were collected over 1 min at every sampling time for 12 h 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 (T(i)) were determined. To characterize the pharmacokinetics of caffeine, MRT-T(i) values of patch and solution preparations were compared. Patch preparations had a T(i) value of 2.33+/-0.33 h and showed significantly longer MRT-T(i), 3.87+/-0.21 h, as compared to the control preparation (MRT-T(i)=1.04+/-0.38 h) under fasting condition (p<0.05). Food intake prolonged the gastric emptying time (GET) of the preparations with T(i) values of 5.00+/-1.15 h for control preparation and 4.67+/-1.20 h for patch preparation. The MRT-T(i) values were 0.62+/-0.20 h (control) and 2.45+/-0.73 h (patch). The results of this study indicate that the parameter, MRT-T(i), was useful in characterizing the transit characteristics of oral patch preparations than MRT itself and the presence of food affects the performance of the patch system.