2001 Volume 61 Issue 2 Pages 47-58
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.
