SOLUBILITY OF DRUG SUBSTANCES IN LIPOPHIL IC SOLVENTS

A method for determination of drug substances solubility in lipophilic solvents is presented. The solubility was determined in lipophilic su ppository bases meltings, in pharmaceutical lipoides as Oleum Ricini, Oleum Arachidis, Cera perliquida, Paraffinum perliquidum and in chemic ally defined lipoides as n-hexadecane, 1-hexadecene, cetylic alcohol, palmitic acid, cetylpalmitate. Consequences from chemical constitution of substances for solubility are discussed, also consequences from ch emical constitution and dielectric constantes of lipoidic solvents for their solution behavior. For the substances investigated, the apparen t partition coefficients in the two-phase systems lipoide/phosphate bu ffer pH 7,4 and n-octanol/phosphate buffer pH 7,4 were determined, als o the solubility in phosphate buffer. The results show, that connectio ns between partition coefficients and solubility in lipophilic or aque ous phases do not exist. On the other hand, an indirect proportionalit y between water solubility and lipoid solubility also does not exist. In consequence, interpretations of drug release from lipophilic system es have to be proceeded from exact knowledge of partition behavior and solubilities in both the lipophilic and aqueous phase.