The effect of the coexistence of aminophylline on the disintegration behavior of enteric-coated tablets in a pH 1.2 test solution was investigated. When the surfaces of the omeprazole and aminophylline tablets contacted each other and stored at 30°C for 28 days, the disintegration time of the omeprazole tablet was significantly shortened, indicating that the characteristics of the enteric-coated tablet were lost. The release of gaseous ethylenediamine (EDA) from the aminophylline tablet was determined by gas analysis. The higher and longer the storage temperature and time were, the more EDA released. Furthermore, from Fourier transform infrared spectroscopy, it was suggested that cellulose acetate hydrogen phthalate, which is an ingredient of the enteric film coated on the omeprazole tablet interacted with EDA during storage.

The purpose of this study was to establish an appropriate method for evaluating oral dosage forms in beagle dogs by examining the effects of feeding manners and food conditions on the transition of granules in the gastrointestinal (GI) tract. Three-hundred particles of indisintegrable granules 1-2 mm in length were administered to dogs in the fasted state, or after or during a liquid or solid meal. The transition of the granules was examined by anatomical observation under anesthesia. Almost all the granules administered during a meal were emptied from the stomach within 3 h in the liquid meal group, while in the solid meal group, half of the granules remained in the stomach (liquid meal > solid meal). The gastric emptying (GE) rates of the granules administered during a meal were slower than when administered after a meal (after meal > during meal). The GE pattern after a solid meal resembled that of humans. The residence time of granules in the small intestine was about 1 h in all cases and was shorter than that of humans (4 h). The results of GI transition of the granules after the liquid meal, studied by using enteric-coated granules of acetaminophen and salicylazosulfapyridine as markers of GE and arrival at the colon, respectively, were almost the same as those obtained by anatomical observation. The GE rate of granules can be changed by feeding timing and food conditions, and the inter-individual variance in the GE profile of granules and pH of luminal fluid after a liquid meal were the smallest. This indicated that this feeding manner is appropriate for evaluating oral dosage forms.

Since the lipophilic basic compound S-2150 displays markedly low solubility in the pH range above 4.4, its dissolution rate and permeability across the gastrointestinal (GI) membrane are considered to vary depending on the pH and luminal fluid volume along the GI tract. We used a gastric emptying (GE)-convolution method to simulate the in vivo dissolution profiles of enteric-coated S-2150 granules after administration to dogs. In this method, the GE rate of the granules was calculated from the cumulative absorption after the administration of acetaminophen enteric-coated granules. The weighing function was the in vitro dissolution profile obtained in a pH 6.0 test solution with the assumption that the dissolution would terminate after a granule residence time (20 min) at the effective release/absorption site in the GI tract. The simulated in vivo dissolution profiles agreed well with the absorption profiles, and a good in vitro / in vivo correlation (IVIVC) was achieved. The present procedure is a straightforward way of predicting the bioavailability of various multiple-unit type enteric-coated formulations. It is useful for designing and/or optimizing evaluation methods and also to obtain a good IVIVC.

Ground mixtures of halopredone acetate (HA), a poorly water-soluble drug, with tamarind gum (TG) were prepared for the improvement of solubility. The dissolution property of HA in the ground mixture was studied by an in vitro release test using dialysis membrane. Also, the ground mixture was evaluated using experimental allergic rhinitis models in rats. Crystalline HA became amorphous by grinding with TG. The amount of HA released from ground mixture was about five times that of the intact mixture. The ground mixture inhibited symptoms of allergic rhinitis in rats, but the intact mixture did not. This result suggests that HA formulation prepared by grinding with TG should be useful.