A new therapeutic drug of cerebrovascular disorders, (E)-1-(3-fluoro-6, 11-dihydrodibenz [b,e]oxepin-11-yl)-4-(3-phenyl-2-propenyl) piperazine dimaleate (AJ-3941), is practically insoluble in water and unstable in acidic media. The solid dispersions with an enteric polymer, such as hydroxypropylmethylcellulose phthalate (HPMCP), hydroxypropylmethylcellulose acetate succinate (HPMC-AS), and Eudragit L100 (Eud), carboxymethylethylcellulose (CMEC), and a water soluble polymer, such as hydroxypropylcellulose (HPC-L), hydroxypropylmethylcellulose (HPMC), and polyvinylpyrrolidon (PVP) with enteric membrane were prepared. It was observed by a powder X-ray diffractometry and a differential scanning calorimetry that AJ-3941 was present in the amorphous form. These preparations showed good dissolution properties and good bioavailability after oral administrations to dogs. AJ-3941 in these preparations, using an enteric polymer was unstable in an aluminum package at 40°C and 75% relative humidity, but in these preparations the use of a water soluble polymer was stable in the aluminum package. These preparations may be a useful means to improve the bioavailability and stability of AJ-3941. Furthermore, we tried to prepare the solid dispersion by the spray-drying method without dichloromethane. The preparation using PVP had the same characteristics as the one prepared by using dichloromethane. It was therefore suggested that this method could be useful for the preparation of solid dispersions of AJ-3941 without the use of poisonous dichloromethane.

Complexations between opposite-charged dextran derivatives were investigated focusing on an application as a device of sustained or controlled-release drug delivery systems. Dextran and its derivatives are naturally occurring polysaccharides with biocompatibility and are used in pharmaceutical and cosmetic fields. Carboxymethyldextran (CMD) and dextran sulfate (DS) were used as a polyanion, and [2-(diethylamino) ethyl] dextran (EA) and [2-hydroxypropyltrimethylanmonium] dextran (CDC) as a polycation. Each polyelectrolyte was characterized by potentiometric titrations. The complex formation was followed by turbidity measurement in the media of various pH values and FT/IR spectroscopy in the solid state. The formation of the complexes was dependent on pH values in the reaction mixture in CMD/EA, CMD/CDC and DS/EA systems, except in DS/CDC. At pH 1.2 and 2.0, no complex was formed in CMD/EA and CMD/CDC systems because of no dissociation of CMD molecules in the acidic media. A maximum turbidity shifted from the greater weight fraction of polyanion to the lower one as an increase of pH values. At pH 6.8, the maximum turbidity was observed at the weight ratio of 7:13 in CMD/EA and CMD/CDC, and at 1:3 in DS/EA and DS/CDC. No complex was formed stoichiometrically in DS/EA and DS/CDC systems because of the high degree of substitution on DS. FT/IR spectroscopy suggested that the N(C₂H₅)₂⁺ groups in EA molecules interacted with COO^- and SO₃^- groups in CMD and DS, respectively.

Effective levels of antimicrobial drugs are required for the successful eradication of Helicobacter pylori (H. pylori) from the gastric mucosa. We examined the stabilities of two typical anti-H. pylori drugs, amoxicillin (AMX) and metronidazole (MZ), in artificial gastric juice (pH 1.2 or pH 4.0). We administered the drugs to mice parenterally or orally (po) and investigated the efficacy of their delivery at the gastric mucosa. MZ degraded only slightly in the artificial gastric solutions, while AMX was unstable in acidic conditions. Delivery to the gastric mucosa was scarcely observable in the case of parenteral AMX administration. However, delivery was readily detectable after po delivery of the suspension, although serum concentration was lower than with intraperitoneal injection. MZ was delivered to gastric mucosa after intravenous injection, and the amount increased according to the serum MZ level. The concentration of MZ in the gastric mucosa after po administration was greater than with parenteral administration.