Dissolution improvement of RS-8359 by the solid dispersion prepared by the solvent method

Abstract

Study on dissolution improvement of a water-insoluble compound, RS-8359 ((±)-4-(4-cyanoanilino)-5,6-dihydro-7-hydroxy-7H-cyclopenta[ d]pyrimidine) was carried out. A hydrochloric acid salt of RS-8359 had much higher solubility than its free form. However, the free form separated out of a neutral buffer solution instantaneously once the salt form was dissolved. We found that the dissolution properties were greatly improved by preparing a solid dispersion of the salt form with a water-soluble polymer mainly because the dissolved water-soluble polymer included in the solid dispersion retarded the precipitation rate of the free form. The crystallinity of the salt form in the solid dispersion did not affect the dissolution properties greatly. Furthermore, the importance of microenvironmental pH in the solid dispersion was suggested by a significant increase in the maximum concentration of RS-8359 in the dissolution process of the solid dispersion as compared with the case that the simple salt form was dissolved in the buffer solution that included the water-soluble polymer.