This project describes the activities of the formulation laboratory of the Pharmaceutical Resources Branch. These studies are directed toward resolving problems in the intravenous delivery of antitumor agents and involve methods to evaluate and then improve drug solubility and stability. Pharmaceutical aspects of the new platinum analogue, tetraplatin, were examined. Stability-indicating HPLC methods were devloped and applied to an evaluation of this compound under a variety of conditions and a freeze dried dosage form was developed. The safety of certain antitumor agents has been a topic of considerable concern to personnel involved with the handling and administration of these compounds. Procedures to decompose (two-three log reduction) fourteen compounds have been developed using simple procedures: base, hydrogen peroxide, and/or heat. These compounds represent most of the chemical categories of clinically active antitumor agents. Methods to improve drug solubility have also been evaluated. Several water soluble prodrugs of camptothecin have been prepared and evaluated in suitable tumor models. The N,N-diethyl glycine deriviative exhibited activity and potency similar to that demonstrated by camptothecin. Also the influence of the polymer, poly 1-methionine sulfoxide on the solubility of several antitumor agents was studied.
