Risarestat

Pharmaceutical preparation of a hydrophobic aldose reductase inhibitor 5-(3-ethoxy-4-pentyloxyphenyl)-2,4-thiazolidinedione (CT112) was investigated. CT112 dissolved in a basic solution with different kinds of polymers was neutralized by acid to obtain a suspension preparation. In particular, the addition of a polymer, hydroxypropyl methyl cellulose (HPMC) provided a stable CT112 suspension with a homogeneous particle size, and there seemed to be an optimal concentration of HPMC for the stable suspension. The addition of polysorbate 80 brought higher CT112 solubility in water, but did not provide a stable suspension. X-ray diffraction, IR spectrum, and thermal analysis revealed that the particles in the suspension with HPMC had lower degree of crystallinity, less hydrophobic particle surface, and lower melting point and decreased fusion enthalpy than the suspension without HPMC. These results suggested that the highly stable CT112 suspension could be attained by the adsorption of the polymer.

Aqueous suspensions of 5-(3-ethoxy-4-pentyloxyphenyl)-2,4-thiazolidinedione (CT 112) have been prepared by neutralization of alk. solutions of CT 112 in the presence of surfactant/polymer with HCl.SDS and celluloses have been used.The effect of dilution of water on the aqueous CT 112 dispersion has been studied by measuring the amount adsorbed of surfactant and polymer, ζ-potential, particle size, and sedimentation behavior.The dispersion stability of aqueous CT 112 suspension in the presence of polymer or SDS by dilution of water depends on the initial concentration of polymer or SDS.On the other hand, the dispersion stability of aqueous CT 112 suspension in the presence of both polymer and SDS is stable even by dilution of water.The mechanism for the effect of dilution of water has been discussed.